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Sample records for normal aging brain

  1. Brain cholesterol in normal and pathological aging.

    Science.gov (United States)

    Martin, Mauricio; Dotti, Carlos G; Ledesma, Maria Dolores

    2010-08-01

    Correct lipid homeostasis at the plasma membrane is essential for cell survival and performance. These are critically challenged in the aging brain. Changes in the levels of cholesterol, a major membrane component especially enriched in neurons, accompany the brain aging process. They also occur in neurodegenerative diseases. Understanding the causes and consequences of these changes is a crucial step when trying to delay the cognitive decline, which comes with age, or to design strategies to fight neurodegenerative disorders such as Alzheimer's disease. We here review work that has contributed to this understanding. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Functional neuroimaging of normal aging: Declining brain, adapting brain.

    Science.gov (United States)

    Sugiura, Motoaki

    2016-09-01

    Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Brain cholesterol in normal and pathological aging

    NARCIS (Netherlands)

    T. Vanmierlo (Tim); D. Lütjohann (Dieter); M.T. Mulder (Monique)

    2011-01-01

    textabstractAberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration,

  5. A longitudinal study of brain volume changes in normal aging

    International Nuclear Information System (INIS)

    Takao, Hidemasa; Hayashi, Naoto; Ohtomo, Kuni

    2012-01-01

    Purpose: To evaluate the effect of normal aging on brain volumes and examine the effects of age and sex on the rates of changes in global and regional brain volumes. Methods: A total of 199 normal subjects (65 females and 134 males, mean age = 56.4 ± 9.9 years, age range = 38.1–82.9 years) were included in this study. Each subject was scanned twice, at an interval of about 2 years (range = 1.5–2.3 years). Two-time-point percentage brain volume change (PBVC) was estimated with SIENA 2.6. Results: The mean annualized PBVC was −0.23%/y. Analysis of covariance (ANCOVA) for annual brain volume changes revealed a main effect of age. There was no main effect of sex, nor was there a sex-by-age interaction. Voxel-wise analysis revealed a negative correlation between age and edge displacement values mainly in the periventricular region. Conclusions: The results of our study indicate that brain atrophy accelerates with increasing age and that there is no gender difference in the rate of brain atrophy

  6. Determinants of iron accumulation in the normal aging brain.

    Science.gov (United States)

    Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2016-07-01

    In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. What is ''normal aging brain for his/her age'' ? The first report

    International Nuclear Information System (INIS)

    Taki, Yasuyuki; Kinomura, Shigeo; Goto, Ryoi

    2005-01-01

    We evaluated the correlations between the gray matter volume, white matter volume and age, and determined normal aging brain for his/her age in every decade. We analyzed magnetic resonance images of the brain from 828 normal Japanese subjects. Significant negative correlation between the gray matter ratio (ratio of the gray matter volume in intracranial volume) and age was shown. From these results, we determined ''normal aging brain for his/her age'' and ''atrophied brain for his/her age'' in every decade. (author)

  8. Sex differences in normal age trajectories of functional brain networks.

    Science.gov (United States)

    Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

    2015-04-01

    Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

  9. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    International Nuclear Information System (INIS)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M.; Poole, Ian; Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D.

    2012-01-01

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged ≥60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged ≥60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  10. Increased self-diffusion of brain water in normal aging

    DEFF Research Database (Denmark)

    Gideon, P; Thomsen, C; Henriksen, O

    1994-01-01

    With magnetic resonance (MR) imaging, brain water self-diffusion was measured in 17 healthy volunteers 22-76 (mean, 44.6) years old. The calculated values for the apparent diffusion coefficients (ADCs) ranged from 0.58 x 10(-9) to 1.23 x 10(-9) m2/sec in cerebral white matter. A significant...... correlation was found between the ADC in white matter and age (r = .7069, P age. The increased ADC in white matter may be caused...... by an increase in the extracellular volume due to age-dependent neuronal degeneration or to changes in myelination. These findings have implications for future clinical investigations with diffusion MR imaging techniques in patients with neurologic diseases, and stress the importance of having an age...

  11. Brain lipopigment accumulation in normal and pathological aging.

    Science.gov (United States)

    Riga, Dan; Riga, Sorin; Halalau, Florin; Schneider, Francisc

    2006-05-01

    A principal marker of brain vulnerability, stress, aging, and related pathology is represented by lipopigments (LPs)--lipofuscin, and ceroid. During ontogenesis, neuronal LP accumulations are significantly correlated with important changes in nerve cell morphology and biochemistry. In the aged neurons, LPs are present in all cellular compartments. Moreover, neuronal LP accumulations coexist with glial LP storage, especially in microglia. Owing to their transporting properties, and the migration capacity of microglia, glial cells deposit LP clusters in pericapillary areas. Thus, LP conglomerates appear in the whole nervous tissue, creating specific patterns of LP architectonics. Direct interrelations, critical LP concentrations, which generate cascades of negative subcellular events, and indirect impairment correlations determine characteristic neuropathologic aging profiles. These specific and associated negative neuropathologic consequences of LP accumulation have multiple and detrimental impacts on neuron and glia homeostasis, ranging from neuronal function to central nervous system physiology.

  12. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging.

    Science.gov (United States)

    Dushanova, Juliana; Christov, Mario

    2013-05-25

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone - right hand movement and high frequency tone - left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  13. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  14. Association of structural global brain network properties with intelligence in normal aging.

    Directory of Open Access Journals (Sweden)

    Florian U Fischer

    Full Text Available Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  15. Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

    Science.gov (United States)

    Fischer, Florian U.; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience. PMID:24465994

  16. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    Energy Technology Data Exchange (ETDEWEB)

    Naganawa, Shinji; Ishigaki, Takeo [Department of Radiology, Nagoya University School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 466-8550 (Japan); Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo [Department of Radiology, First Kamiida General Hospital (Japan)

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean{+-}standard deviation 2.3{+-}1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

  17. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Ishigaki, Takeo; Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean±standard deviation 2.3±1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

  18. R2* mapping for brain iron: associations with cognition in normal aging.

    Science.gov (United States)

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. A longitudinal study of structural brain network changes with normal aging

    Directory of Open Access Journals (Sweden)

    Kai eWu

    2013-04-01

    Full Text Available The aim of this study was to investigate age-related changes in the topological organization of structural brain networks by applying a longitudinal design over 6 years. Structural brain networks were derived from measurements of regional gray matter volume and were constructed in age-specific groups from baseline and follow-up scans. The structural brain networks showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection costs. In the analysis of the global network properties, the local and global efficiency of the baseline scan were significantly lower compared to the follow-up scan. Moreover, the annual rate of changes in local and global efficiency showed a positive and negative quadratic correlation with the baseline age, respectively; both curvilinear correlations peaked at approximately the age of 50. In the analysis of the regional nodal properties, significant negative correlations between the annual rate of changes in nodal strength and the baseline age were found in the brain regions primarily involved in the visual and motor/ control systems, whereas significant positive quadratic correlations were found in the brain regions predominately associated with the default-mode, attention, and memory systems. The results of the longitudinal study are consistent with the findings of our previous cross-sectional study: the structural brain networks develop into a fast distribution from young to middle age (approximately 50 years old and eventually became a fast localization in the old age. Our findings elucidate the network topology of structural brain networks and its longitudinal changes, thus enhancing the understanding of the underlying physiology of normal aging in the human brain.

  20. Classification of normal and pathological aging processes based on brain MRI morphology measures

    Science.gov (United States)

    Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.

    2014-03-01

    Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.

  1. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    International Nuclear Information System (INIS)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S.

    1998-01-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.)

  2. Positron emission tomography studies in the normal and abnormal ageing of human brain

    International Nuclear Information System (INIS)

    Comar, D.; Baron, J.C.

    1987-01-01

    Until recently, the investigation of the neurophysiological correlates of normal and abnormal ageing of the human brain was limited by methodological constraints, as the technics available provided only a few parameters (e.g. electroencephalograms, cerebral blood flow) monitored in superficial brain structures in a grossly regional and poorly quantitative way. Lately several non invasive techniques have been developed which allow to investigate in vivo both quantitatively and on local basis a number of previously inaccessible important aspects of brain function. Among these techniques, such as single photon emission tomography imaging of computerized electric events, nuclear magnetic resonance, positron emission tomography stands out as the most powerful and promising method since it allows the in vivo measurement of biochemical and pharmacological parameters

  3. Brain regional uptake of radioactive Sc, Mn, Zn, Se, Rb and Zr tracers into normal mice during aging

    International Nuclear Information System (INIS)

    Amano, R.; Enomoto, S.

    2001-01-01

    Radioactive multitracer technique was applied to study the brain regional uptake of trace elements by the normal mice during aging. The brain regional radioactivities of 46 Sc, 54 Mn, 65 Zn, 75 Se, 83 Rb and 88 Zr were measured 48 hours after intraperitoneal injection of a solution in normal mice aged 6 to 52 weeks to evaluate the brain regional (corpus striatum, cerebellum, cerebral cortex, hippocampus, and pons and medulla) uptakes. The radioactive distributions of 46 Sc, 54 Mn and 88 Zr tracers were variable and region-specific in the brain, while those of 65 Zn, 75 Se and 83 Rb tracers were comparable among all regions of interest. The brain regional uptakes of all tracers slightly increased with age from 10 to 28 weeks, and then remained constant during aging after 28 weeks. These uptake variations may be involved in the functional degenerative process of the blood-brain barrier during aging. (author)

  4. Brain aging in normal Egyptians: cognition, education, personality, genetic and immunological study.

    Science.gov (United States)

    Elwan, Osamah; Madkour, Obsis; Elwan, Fadia; Mostafa, Mervat; Abbas Helmy, Azza; Abdel-Naseer, Maged; Abdel Shafy, Sanaa; El Faiuomy, Nervana

    2003-07-15

    Studying the cognitive and immunological changes that occur in old age as well as genetic function have been considered an important subject to differentiate between normal brain aging and early dementia especially Alzheimer's disease. The aim of this study is to stress on age-related neuropsychological and electrophysiological (P(300)) changes in normal Egyptian subjects, to throw light on the value of genetic (Apo-E(4) genotype) and immunological markers [interleukin-6 (IL-6) and intercellular adhesion molecules (ICAM-1) in the serum] as tools used in early detection of cognitive decline in cerebral aging. Ninety-four normal Egyptian subjects (below and above 60 years) were submitted to the following: (1) neuropsychological tests for testing memory, perception, psychomotor performance and attention, (2) Eysenck Personality Questionnaire (EPQ) for personality traits, (3) event-related potential study (P(300), latency and amplitude), (4) genetic test for detection of Apolipoprotein E genotype and (5) immunological studies including detection of the level of IL-6 and ICAM-1 in serum. There was a significant impairment of memory, psychomotor performance and perception in elderly subjects particularly males and subjects with low level of education. Regarding personality, significantly high scores were obtained in neuroticism scale of EPQ in elderly subjects. Apo-E(3)/E(3) was the most common genotype encountered in Egyptian subjects (49.1%). It was found that subjects with Apo-E(4) genotype did significantly worse in scores of intentional memory test (sensory memory) when compared with other genotypes. Statistically significant impairment in attention and sensory memory was found in subjects with high IL-6 level. This could not be detected in subjects with high ICAM-1 level. In conclusion, advancing age and lower levels of education are considered risk factors for cognitive decline in normal brain aging. Neuropsychological tests remain as the highly sensitive tools

  5. Acetylome regulation by sirtuins in the brain: from normal physiology to aging and pathology.

    Science.gov (United States)

    Michan, Shaday

    2013-01-01

    Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the "acetylome." At present, it is estimated that acetylome covers only one tenth of the proteome, however, due its potential significance in physiology is capturing great attention. The first components of the cellular machinery, which finely orchestrate acetylome homeostasis, were identified by the end of last century. Since then, the majority of our growing knowledge concerning the physiological relevance of proteome reversible acetylation comes from the study of sirtuins, a unique type of lysine deacetylase that uses NAD(+). Sirtuins participate in a variety of cellular processes, ranging from transcription, DNA repair, energy balance, mitochondrial biogenesis and cell division, to apoptosis, autophagy and aging. Within the brain, besides their widespread epigenetic effects of dynamically modifying histones, sirtuins also target a variety of non-histone proteins either commonly deregulated in pathologies, or that participate in normal cerebral functions. For example, they modulate critical elements of the circadian rhythms, neurogenesis, synapses, cognition, serotonin synthesis, myelination, and proteins involved in neuropathology. Acetylome dynamics, and its regulation by sirtuins, may also help to better understand the molecular mechanisms underlying brain aging. This work reviews the pathways as orchestrated by the interplay between acetylome and sirtuins in the brain, from physiology involvement, to aging processes, and pathological settings.

  6. Trail Making Test in traumatic brain injury, schizophrenia, and normal ageing: sample comparisons and normative data.

    Science.gov (United States)

    Periáñez, J A; Ríos-Lago, M; Rodríguez-Sánchez, J M; Adrover-Roig, D; Sánchez-Cubillo, I; Crespo-Facorro, B; Quemada, J I; Barceló, F

    2007-05-01

    The Trail Making Test (TMT) has been a useful assessment tool to investigate executive function. Several studies have recently improved the existing TMT norms by mean of large samples of healthy individuals stratified by a number of demographic variables from different populations. In contrast, criticisms have been raised about the utility of norms from healthy samples to detect changes across time in clinical samples where TMT performance used to be altered. In addition, few studies have compared groups of patients with deficits in TMT performance, making it difficult to decide whether a single set of norms is sufficient to assess different clinical populations. We provide normative data from three large samples of patients with traumatic brain injury (TBI) (n=90), schizophrenia spectrum disorders (n=127), and healthy Spanish speakers (n=223). Differences between healthy participants and patients in all TMT direct (TMT-A, TMT-B) and derived (B-A, B:A, B-A/A) scores were found. TMT performance was poorer in TBI patients than in schizophrenia patients except for the B:A and B-A/A scores, suggesting a similar underlying executive deficit. Normal ageing impaired both direct and derived TMT indices, as revealed by lower scores in the healthy elderly group (55-80 years old) as compared with young (16-24) and middle-aged (25-54) healthy participants. Three different sets of norms stratified by age, education, or both are presented for clinical use. Recommendations on TMT scores are made for future research.

  7. Gene expression changes in the course of normal brain aging are sexually dimorphic

    Science.gov (United States)

    Berchtold, Nicole C.; Cribbs, David H.; Coleman, Paul D.; Rogers, Joseph; Head, Elizabeth; Kim, Ronald; Beach, Tom; Miller, Carol; Troncoso, Juan; Trojanowski, John Q.; Zielke, H. Ronald; Cotman, Carl W.

    2008-01-01

    Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20–99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea. PMID:18832152

  8. Modeling the effects of age and gender on normal pediatric brain metabolism using F18-FDG PET/CT.

    Science.gov (United States)

    Turpin, Sophie; Martineau, Patrick J; Levasseur, Marc-André; Lambert, Raymond

    2017-12-28

    Normal databases of pediatric brain metabolism are uncommon, as local brain metabolism evolves significantly with age throughout childhood, limiting their clinical applicability. The aim of this study was to develop mathematical models of regional relative brain metabolism (RRBM) using pediatric F18-FluoroDeoxyGlucose (FDG) Positron Emission Tomography (PET) with Computed Tomography (CT) data of normal pediatric brains, accounting for gender and age. Methods: PET/CT brain acquisitions were obtained from 88 neurologically-normal subjects, aged 6 months to 18 years. Subjects were assigned to either development ( n = 59) or validation groups ( n = 29). For each subject, commercially available software (NeuroQTM) was used to quantify the relative metabolism of 47 separate brain regions using whole-brain normalized (WBN) and pons normalized (PN) activity. The effects of age on RRBM were modeled using multiple linear and non-linear mathematical equations and the significance of gender was assessed using the Student t-test. Optimal models were selected using the Akaike Information Criterion. Mean predicted values and 95% prediction intervals were derived for all regions. Model predictions were compared to the validation data set and mean predicted error was calculated for all regions using both WBN and PN models. Results: As a function of age, optimal models of RRBM were linear for 7 regions, quadratic for 13, cubic for 6, logarithmic for 12, power for 7, and modified power laws for 4regions using WBN data; linearfor 9 regions, quadratic for 27, cubic for 2, logarithmic for 5 and power for 2 using PN data. Gender differences were found to be statistically significant only in the posterior cingulate cortex for the WBN data. Comparing our models to the validation group resulted in 94.3% of regions falling within the 95% prediction interval for WBN and 94.1% for PN. For all the brain regions in the validation group, the percentage of error in prediction was 3 ± 0.96% using

  9. Prospective microglia and brain macrophage distribution pattern in normal rat brain shows age sensitive dispersal and stabilization with development.

    Science.gov (United States)

    Ghosh, Payel; Mukherjee, Nabanita; Ghosh, Krishnendu; Mallick, Suvadip; Pal, Chiranjib; Laskar, Aparna; Ghosh, Anirban

    2015-09-01

    The monocytic lineage cells in brain, generally speaking brain macrophage and/or microglia show some dissimilar distribution patterns and disagreement regarding their origin and onset in brain. Here, we investigated its onset and distribution/colonization pattern in normal brain with development. Primarily, early and late embryonic stages, neonate and adult brains were sectioned for routine H/E staining; a modified silver-gold staining was used for discriminating monocytic lineage cells in brain; and TEM to deliver ultramicroscopic details of these cells in brain. Immunofluorescence study with CD11b marker revealed the distribution of active microglia/macrophage like cells. Overall, in early embryonic day 12, the band of densely stained cells are found at the margin of developing ventricles and cells sprout from there dispersed towards the outer edge. However, with development, this band shrunk and the dispersion trend decreased. The deeply stained macrophage like cell population migration from outer cortex to ventricle observed highest in late embryonic days, continued with decreased amount in neonates and settled down in adult. In adult, a few blood borne macrophage like cells were observed through the vascular margins. TEM study depicted less distinguishable features of cells in brain in early embryo, whereas from late embryo to adult different neuroglial populations and microglia/macrophages showed distinctive features and organization in brain. CD11b expression showed some similarity, though not fully, with the distribution pattern depending on the differentiation/activation status of these macrophage lineage cells. This study provides some generalized spatial and temporal pattern of macrophage/microglia distribution in rat brain, and further indicates some intrigue areas that need to be addressed.

  10. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample

    Directory of Open Access Journals (Sweden)

    Chaves M.L.F.

    1999-01-01

    Full Text Available The main objective of the present study was to evaluate the diagnostic value (clinical application of brain measures and cognitive function. Alzheimer and multiinfarct patients (N = 30 and normal subjects over the age of 50 (N = 40 were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.

  11. Age-related deposition of brain iron in normal adults: an in vivo susceptibility weighted imaging study

    International Nuclear Information System (INIS)

    Wang Qidong; Xu Xiaojun; Zhang Minming

    2008-01-01

    Objective: The purpose of this study was to investigate the effect of age on the iron concentration of the human brain. Methods: The brain iron level was evaluated in vivo in 78 healthy adult volunteers using a noninvasive magnetic resonance method termed susceptibility weighted imaging. The subjects were divided intothree groups due to different ages: young (22-35 years old, n=27), middle- aged (36-55 years old, n=35), and aged (56-78 years old, n=16). The phase values were measured on the corrected phase images in the globus pallidus, putamen, caudate, substantia nigra, red nucleus, thalamus and frontal white matter. The phase values of those regions measured from the subjects over than 30 years old were correlated with published values of brain iron concentration in normal adults to check the validity of the data. Then, the phase values of the three groups were tested for significant age-related differences using one-way ANOVA, followed by post hoc testing using least significant difference (LSD) procedure. Regression analysis was used to further examine age-related effects revealed by group comparisons, and to estimate the rates of age-related changes. Results: A strong negative correlation was found between the phase values and the published values of the brain iron concentration (r=-0.796, P= 0.032), which indicated that the higher the iron deposition level, the greater the negative phase values. In the putamen (F=20.115, P<0.01) and frontal white matter (F=3.536, P=0.034), significant differences were detected in the phase values of the three age groups. Linear regression analysis showed that phase values of the putamen, frontal white matter, and red nucleus decreased with age (The regression coefficients were -0.001, -0.001, and < -0.001 respectively, and the P value were all < 0.05), which indicated that the iron concentration of those brain structures increased with age. No significant age- related changes of the iron concentration were found in the

  12. Biphasic and region-specific MAO-B response to aging in normal human brain.

    Science.gov (United States)

    Saura, J; Andrés, N; Andrade, C; Ojuel, J; Eriksson, K; Mahy, N

    1997-01-01

    Variations of monoamine oxidases (MAO) A and B were studied during aging in 27 human subjects (age range 17-93 years) in 18 brain structures of temporal cortex, frontal gyrus, hippocampal formation, striatum, cerebellum, and brainstem. [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. Postmortem delay or time of tissue storage did not affect MAO-A or MAO-B levels. There was, moreover, no evidence of sexual dimorphism. A marked age-related increase in MAO-B was observed in most structures. This increase started at the age of 50-60 years. Before this age, MAO-B levels were constant in all structures studied. MAO-B-rich senile plaques were observed in some cortical areas but they did not significantly influence the age-related MAO-B increase. Surprisingly, no age-related MAO-B changes were observed in the substantia nigra. In contrast to MAO-B, no clear age-related changes in MAO-A were observed, indicating an independent regulation of the two isoenzymes, also suggested by the cross-correlation analysis of these data.

  13. Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: Relation with normal brain development and aging

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Toshiyuki; Sakuma, Hajime; Takeda, Kan; Tagami, Tomoyasu; Okuda, Yasuyuki; Nakagawa, Tsuyoshi (Mie Univ. School of Medicine (Japan))

    1994-02-01

    To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. Ten neonates (<1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin-echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. Diffusion-weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. 18 refs., 6 figs., 1 tab.

  14. MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping.

    Science.gov (United States)

    Bilgic, Berkin; Pfefferbaum, Adolf; Rohlfing, Torsten; Sullivan, Edith V; Adalsteinsson, Elfar

    2012-02-01

    versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Effects of sex and normal aging on regional brain activation during verbal memory performance

    Science.gov (United States)

    Hazlett, Erin A.; Byne, William; Brickman, Adam M.; Mitsis, Effie M.; Newmark, Randall; Haznedar, M. Mehmet; Knatz, Danielle T.; Chen, Amy D.; Buchsbaum, Monte S.

    2010-01-01

    This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using 18FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20–87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate—a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change. PMID:19027195

  16. Effects of sex and normal aging on regional brain activation during verbal memory performance.

    Science.gov (United States)

    Hazlett, Erin A; Byne, William; Brickman, Adam M; Mitsis, Effie M; Newmark, Randall; Haznedar, M Mehmet; Knatz, Danielle T; Chen, Amy D; Buchsbaum, Monte S

    2010-05-01

    This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using (18)FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20-87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate--a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change. (c) 2008 Elsevier Inc. All rights reserved.

  17. Age-dependent changes in metabolites of the normal brain in childhood. Observation by proton MR spectroscopy

    International Nuclear Information System (INIS)

    Tanouchi, Miki; Harada, Masafumi; Hashimoto, Toshiaki; Nishitani, Hiromu

    1996-01-01

    We investigated aging-dependent changes in proton magnetic resonance spectroscopy ( 1 H-MRS) of the normal brain in childhood, and observed differences in the four portions of the brain. Measurement by 1 H-MRS was carried out on the frontal lobe, parietotemporal lobe, temporal lobe and cerebellum. The NAA/Cho ratio increased rapidly in the period from 0 to 2 years of age in all portions except for the cerebellum, and gradually increased after three years of age. The number of measurements of the cerebellum was not sufficient to reach a conclusion, but no clear aging-related change was found. The Cho/Cr ratio decreased according to the neural development in all portions except the cerebellum. Because the T2 relaxation time of water after four years of age was almost the same as that of young adults, we used the relaxation times specified in the literature to quantify the metabolites observed by 1 H-MRS. The subjects used for quantification were aged from 4 to 12 years. The concentration of NAA in the temporal lobe was the lowest of the four portions, and that of Cho and Cr in the cerebellum was the highest in four portions. These results could not be obtained by signal ratios alone, and we considered that the quantification of metabolites is necessary for a better understanding of 1 H-MRS. This study showed that the results of 1 H-MRS vary depending on age and the portion in the brain. Our results may serve as a normal basis for the detection of pathological changes by 1 H-MRS. (author)

  18. Transtemporal Investigation of Brain Parenchyma Elasticity Using 2-D Shear Wave Elastography: Definition of Age-Matched Normal Values.

    Science.gov (United States)

    Ertl, Michael; Raasch, Nele; Hammel, Gertrud; Harter, Katharina; Lang, Christopher

    2018-01-01

    The goal of our research was to assess the possibility of reliable investigation of brain tissue stiffness using ultrasonographic brain parenchyma elastography with an intact temporal bone. We enrolled 108 patients after exclusion of intracranial pathology or healthy volunteers. All patients were subdivided by age into groups: 20-40, 40-60 and >60 y. For statistical analysis, the χ 2 test and t-test were used. The mean values, regardless of age and other parameters, were 3.34 kPa (SD = 0.59) on the left side and 3.33 kPa (SD = 0.58) on the right side. We found no correlation between the values, body mass index (r = 0.07, p = 0.48) and sex (t = -0.11, p = 0.91), but we observed a highly significant correlation between the values and age (r = 0.43, p <0.0001). We found ultrasonographic brain parenchyma elastography to be a valid, reproducible and investigator-independent method that reliably determines brain parenchyma stiffness. Normal values should serve as a reference for studies on various intracranial lesions. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  19. Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

    Science.gov (United States)

    Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

    2016-03-01

    Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

  20. Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique: A methodological study of the aging brain

    International Nuclear Information System (INIS)

    Chen, Z.G.; Hindmarsh, T.; Li, T.Q.

    2001-01-01

    Purpose: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Material and Methods: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Results: Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Conclusion: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest

  1. Voxel-based comparison of whole brain gray matter of patients with mild Alzheimer's disease with normal aging volunteers

    International Nuclear Information System (INIS)

    Xie Sheng; Wu Hongkun; Xiao Jiangxi; Wang Yinhua; Jiang Xuexiang

    2006-01-01

    Objective: To detect gray matter abnormalities of whole brain in patients with mild Alzheimer's disease (AD) by voxel-based morphometry (VBM). Methods: Thirteen patients with mild Alzheimer's disease and sixteen normal aging volunteers underwent 3D SPGR scanning. For every subject, data was transferred to PC to be normalized, segmented and smoothed using SPM99. Non-dependent samples T-tests were conducted to compare gray matter' density voxel to voxel between the two groups. Results Significant reductions in gray matter density were found in the bilateral hippocampi and nucleus amygdalae, bilateral insulae, bilateral medial thalami, bilateral rectus gyri, right superior temporal gyms, right caudate nucleus, fight prefrontal lobe, right basal forebrain and portions of right occipital lobe. Conclusion: VBM reveals significant gray matter' reductions of numeral cortices in mild Alzheimer's disease. It can be a useful method to evaluate the anatomical changes in the progress of the disease. (authors)

  2. Aging Brain, Aging Mind.

    Science.gov (United States)

    Selkoe, Dennis J.

    1992-01-01

    Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

  3. Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

    Science.gov (United States)

    Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

    2014-01-01

    Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

  4. Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

    Science.gov (United States)

    Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

  5. Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Solé-Padullés, Cristina; Bartrés-Faz, David; Junqué, Carme; Vendrell, Pere; Rami, Lorena; Clemente, Imma C; Bosch, Beatriu; Villar, Amparo; Bargalló, Núria; Jurado, M Angeles; Barrios, Maite; Molinuevo, Jose Luis

    2009-07-01

    Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables.

  6. Cognition and brain functional aging

    Directory of Open Access Journals (Sweden)

    Hui-jie LI

    2014-03-01

    Full Text Available China has the largest population of elderly adults. Meanwhile, it is one of the countries showing fastest aging speed in the world. Aging processing is always companied with a series of brain structural and functional changes, which result in the decline of processing speed, working memory, long-term memory and executive function, etc. The studies based on functional magnetic resonance imaging (fMRI found certain aging effects on brain function activation, spontaneous activity and functional connectivity in old people. However, few studies have explored the brain functional curve during the aging process while most previous studies explored the differences in the brain function between young people and old people. Delineation of the human brain functional aging curve will promote the understanding of brain aging mechanisms and support the normal aging monitoring and early detection of abnormal aging changes. doi: 10.3969/j.issn.1672-6731.2014.03.005

  7. The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Francesca Cerbai

    Full Text Available Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1 increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.

  8. Normalized Mini-Mental State Examination for assessing cognitive change in population-based brain aging studies.

    Science.gov (United States)

    Philipps, Viviane; Amieva, Hélène; Andrieu, Sandrine; Dufouil, Carole; Berr, Claudine; Dartigues, Jean-François; Jacqmin-Gadda, Hélène; Proust-Lima, Cécile

    2014-01-01

    The Mini-Mental State Examination (MMSE) is widely used in population-based longitudinal studies to quantify cognitive change. However, its poor metrological properties, mainly ceiling/floor effects and varying sensitivity to change, have largely restricted its usefulness. We propose a normalizing transformation that corrects these properties, and makes possible the use of standard statistical methods to analyze change in MMSE scores. The normalizing transformation designed to correct at best the metrological properties of MMSE was estimated and validated on two population-based studies (n = 4,889, 20-year follow-up) by cross-validation. The transformation was also validated on two external studies with heterogeneous samples mixing normal and pathological aging, and samples including only demented subjects. The normalizing transformation provided correct inference in contrast with models analyzing the change in crude MMSE that most often lead to biased estimates of risk factors and incorrect conclusions. Cognitive change can be easily and properly assessed with the normalized MMSE using standard statistical methods such as linear (mixed) models. © 2014 S. Karger AG, Basel.

  9. Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data.

    Science.gov (United States)

    Pagani, Marco; Giuliani, Alessandro; Öberg, Johanna; De Carli, Fabrizio; Morbelli, Silvia; Girtler, Nicola; Arnaldi, Dario; Accardo, Jennifer; Bauckneht, Matteo; Bongioanni, Francesca; Chincarini, Andrea; Sambuceti, Gianmario; Jonsson, Cathrine; Nobili, Flavio

    2017-07-01

    Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18 F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18 F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT and following results were obtained. Brain atrophy was minimal in 34 -- 35 years old in both sexes, increased exponentially to the increasing age after 34 -- 35 years, and probably resulted in dementia, such as vascular or multiinfarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34 -- 35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extents of brain atrophy (20 -- 30 %) existed among aged subjects. Some aged subjects had little or no atrophy of their brains, as seen in young subjects, and others had markedly shrunken brains associated with senility. From these results there must be pathological factors promoting brain atrophy with a great individual difference. We have studied the relation of intelligence to brain volume, and have ascertained that progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was decrease in the cerebral blood flow. MNR-CT can easily detected small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy, while X-CT can not. Therefore NMR-CT is very useful for detection of subtle changes in the brain. (J.P.N.)

  11. Influence of Age on Cerebral Housekeeping Gene Expression for Normalization of Quantitative Polymerase Chain Reaction after Acute Brain Injury in Mice.

    Science.gov (United States)

    Timaru-Kast, Ralph; Herbig, Elina L; Luh, Clara; Engelhard, Kristin; Thal, Serge C

    2015-11-15

    To prevent methodological errors of quantitative PCR (qPCR) normalization with reference genes is obligatory. Although known to influence gene expression, impact of age on housekeeping gene expression has not been determined after acute brain lesions such as traumatic brain injury (TBI). Therefore, expression of eight common control genes was investigated at 15 min, 24 h, and 72 h after experimental TBI in 2- and 21-month-old C57Bl6 mice. Expression of β2-microglobulin (B2M), β-actin (ActB), and porphobilinogen deaminase (PBGD) increased after TBI in both ages. β2M demonstrated age-dependent differences and highest inter- and intragroup variations. Expression of cyclophilin A, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hypoxanthine ribosyltransferase (HPRT), S100B, and 18SrRNA remained stable. Cyclophilin A and HPRT demonstrated strongest inter- and intragroup stability. The data indicate that the expression of most but not all control genes is stable during aging. The correct choice of housekeeping genes is of key importance to ensure adequate normalization of qPCR data. With respect to insult and age, normalization strategies should consider cyclophilin A as a single normalizer. Normalization with two reference genes is recommended with cyclophilin A and HPRT in young mice and in mixed age studies and with cyclophilin A and GAPDH in old mice. In addition, the present study suggests not to use β2-microglobulin, β-actin or PBGD as single control genes because of strong regulation after CCI in 2- and 21-month-old mice.

  12. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  13. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  14. Metabolic changes in the normal ageing brain: Consistent findings from short and long echo time proton spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, S.; Pinker, K. [Department of Diagnostic Radiology, Medical University of Vienna, 1090 Vienna (Austria); MR Centre of Excellence, Medical University of Vienna, 1090 Vienna (Austria); Riederer, F. [Department of Neurology, Medical University of Vienna, 1090 Vienna (Austria); Chmelik, M. [Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna (Austria); MR Centre of Excellence, Medical University of Vienna, 1090 Vienna (Austria); Stadlbauer, A. [Department of Neurosurgery, University of Erlangen-Nuremberg (Germany); Bittsansky, M. [Department of Diagnostic Radiology, Medical University of Vienna, 1090 Vienna (Austria); MR Centre of Excellence, Medical University of Vienna, 1090 Vienna (Austria); Mlynarik, V. [LIFMET, EPFL, Lausanne (Switzerland); Frey, R. [Department of Psychiatry, Medical University of Vienna, 1090 Vienna (Austria); Serles, W. [Department of Neurology, Medical University of Vienna, 1090 Vienna (Austria); Bodamer, O. [Department of Paediatrics, Medical University of Vienna, 1090 Vienna (Austria); Moser, E. [Department of Diagnostic Radiology, Medical University of Vienna, 1090 Vienna (Austria); MR Centre of Excellence, Medical University of Vienna, 1090 Vienna (Austria); Centre for Biomedical Engineering and Physics, Medical University of Vienna, 1090 Vienna (Austria)], E-mail: ewald.moser@meduniwien.ac.at

    2008-11-15

    Objectives: Sixty three healthy subjects were measured to assess dependence of brain metabolites on age using short- and long echo time spectroscopy in different brain regions. Material and methods: Younger and elderly humans were measured with long echo time (TE = 135 ms) 3D-MR-spectroscopic imaging (MRSI) (10 subjects) and with ultra-short echo (TE = 11 ms) time 2D-MRSI (7 subjects). In addition, results from single voxel {sup 1}H-spectroscopy (TE = 20 ms) of two cohorts of 46 healthy subjects were retrospectively correlated with age. Results: 3D-MR SI revealed reduced NAA/Cr in the older group in the frontal lobe (-22%; p < 0.01), parietal lobe (-28%; p < 0.01) and semiovale (-9%; p < 0.01) compared to the younger group. Cho/Cr was elevated in the semiovale (+35%; p < 0.01) and in the n. lentiformis (+42%; p < 0.01) in the older group. NAA/Cho was reduced in all regions measured, except the thalamus, in the older group compared to the younger group (from -21 to -49%; p < 0.01). 2D-MRSI revealed decreased total NAA (-3.1% per decade; p < 0.01) and NAA/Cr (-3.8% per decade; p < 0.01), increased total Cho (+3.6% per decade; p < 0.01) and Cho/Cr (+4.6% per decade; p < 0.01) and increased total myo-Inositol (mI, +4.7% per decade; p < 0.01) and mI/Cr (+5.4% per decade; p < 0.01) and decreased NAA/Cho (-8% per decade; p < 0.01) in semiovale WM. Results from single voxel spectroscopy revealed a significantly negative correlation of NAA/Cho in frontal (-13% per decade; p < 0.01) and in temporal lobe (-7.4% per decade; p < 0.01) as well as increased total Cr (10% per decade; p < 0.01) in frontal lobe. Other results from single voxel measurements were not significant, but trends were comparable to that from multivoxel spectroscopy. Conclusion: Age-related changes measured with long echo time and short echo time 1H-MRS were comparable and cannot, therefore, be caused by different T2 relaxation times in young and old subjects, as suggested previously.

  15. MRI of the normal brain from early childhood to middle age. Pt. 2. Age dependence of signal intensity changes on T2-weighted images

    International Nuclear Information System (INIS)

    Autti, T.; Raininko, R.; Vanhanen, S.L.; Kallio, M.; Santavuori, P.

    1994-01-01

    We examined 66 healthy volunteers aged 4 to 50 years by magnetic resonance imaging (MRI) and the signal intensity was measured on T2-weighted images in numerous sites and correlated with age and sex. Using distilled water and cerebrospinal fluid (CSF) as references on each slice, we calculated the signal intensities of the brain structures. Calculated ratios between structures did not change with age, except for those of the globus pallidus and thalamus, in which the signal intensities decreased more rapidly. The signal intensities of other brain structures changed equally but this could not be discerned visually and quantitative measurements were required. The signal intensities in the white and deep grey matter decreased rapidly in the first decade and then gradually to reach a plateau after the age of 18 years. Maturation of the brain thus seems to continue until near the end of the second decade of life. No sex differences were found. Quantitative analysis requires intensity references. The CSF in the tips of the frontal horns seems to be as reliable as an external fluid reference for intensity, and can be used in routine examinations provided the frontal horns are large enough to avoid partial volume effect. (orig.)

  16. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSBm/m) and C57Bl/6 (WT) controls...... and comparing young (2–5 months) to middle-aged mice (13–14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSBm/m hippocampus, but not in CSBm/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably...... content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSBm/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging....

  17. Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia

    International Nuclear Information System (INIS)

    Hentschel, F.; Kreis, M.; Damian, M.; Krumm, B.; Froelich, F.

    2005-01-01

    Purpose: to quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. Materials and methods: in a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. Results: the WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. Conclusion: a rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia. (orig.)

  18. Different patterns of brain activation in normal aging and Alzheimer's disease from cognitional sight: meta analysis using activation likelihood estimation.

    Science.gov (United States)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; Farhoudi, Mehdi; Talebi, Mahnaz; Mahmoudi, Javad

    2014-08-15

    Alzheimer disease (AD) is a chronic neurological disease, frequently affecting cognitional functions. Recently, a large body of neuro-imaging studies have aimed at finding reliable biomarkers of AD for early diagnosis of disease in contrast with healthy elderlies. We intended to have a meta-analytical study on recent functional neuroimaging studies to find the relationship between cognition in AD patients and normal elderlies. A systematic search was conducted to collect functional neuroimaging studies such as positron emission therapy (PET) and functional magnetic resonance imaging (fMRI) in AD patients and healthy elderlies. The coordinates of regions related to cognition were meta-analyzed using the activation likelihood estimation (ALE) method and Sleuth software. P-value map at the false discovery rate (FDR) of Psize of 200 mm(3) were considered. Data were visualized with MANGO software. Forty-one articles that explored the areas activated during cognition in normal elderly subjects and AD patients were found. According to the findings, left middle frontal gyrus and left precuneus are the most activated areas in cognitional tasks in healthy elderlies and AD patients respectively. In normal elderly subjects and AD patients, comparison of ALE maps and reverse contrast showed that insula and left precuneus were the most activated areas in cognitional aspects respectively. With respect to unification of left precuneus activation in cognitional tasks, it seems that this point can be a hallmark in primary differentiation of AD and healthy individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Insulin and brain aging

    OpenAIRE

    Baranowska-Bik, Agnieszka; Bik, Wojciech

    2017-01-01

    The world’s population is living much longer than in the past. It is crucial to find as many pathological factors that deteriorate the health condition and well-being of elderly people as possible. Loss of activity and functions over time is typical for elderly people. Aging affects brain function, metabolism and structure in different ways, and these effects have multiple etiologies. Cognitive impairment, impaired neurotransmitter activity and reduction of brain volume are observed in th...

  20. Exposure to 56Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory

    Science.gov (United States)

    Shukitt-Hale, Barbara; Casadesus, Gemma; Carey, Amanda N.; Rabin, Bernard M.; Joseph, James A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56Fe, produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as countermeasures to prevent the behavioral changes seen in these conditions. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment, and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a “map” provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere.

  1. [Patterns of brain ageing].

    Science.gov (United States)

    Fernández Viadero, Carlos; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

    2017-06-01

    Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Biology of aging brain

    Directory of Open Access Journals (Sweden)

    Shankar S

    2010-10-01

    Full Text Available Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.

  3. Xenon contrast CT-CBF scanning of the brain differentiates normal age-related changes from multi-infarct dementia and senile dementia of Alzheimer type

    International Nuclear Information System (INIS)

    Tachibana, H.; Meyer, J.S.; Okayasu, H.; Shaw, T.G.; Kandula, P.; Rogers, R.L.

    1984-01-01

    Local cerebral blood flow (LCBF) and partition coefficients (L lambda) were measured during inhalation of stable xenon gas with serial CT scanning among normal volunteers (N . 15), individuals with multi-infarct dementia (MID, N . 10), and persons with senile dementia of Alzheimer type (SDAT, N . 8). Mean gray matter flow values were reduced in both MID and SDAT. Age-related declines in LCBF values in normals were marked in frontal cortex and basal ganglia. LCBF values were decreased beyond normals in frontal and temporal cortices and thalamus in MID and SDAT, in basal ganglia only in MID. Unlike SDAT and age-matched normals, L lambda values were reduced in fronto-temporal cortex and thalamus in MID. Multifocal nature of lesions in MID was apparent. Coefficients of variation for LCBFs were greater in MID compared with SDAT and/or age-matched normals

  4. Neural mechanisms underlying probalistic category learning in normal aging.

    NARCIS (Netherlands)

    Fera, F.; Weickert, T.W.; Goldberg, T.E.; Tessitore, A.; Hariri, A.; Das, S.; Lee, S.; Zoltick, B.; Meeter, M.; Gluck, M.A.; Weinberger, D.A.; Matta, V.S.

    2005-01-01

    Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been

  5. Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

    OpenAIRE

    Chiu, Pui-Wai; Mak, Henry Ka-Fung; Yau, Kelvin Kai-Wing; Chan, Queenie; Chang, Raymond Chuen-Chung; Chu, Leung-Wing

    2013-01-01

    Magnetic resonance spectroscopy (MRS) can explore aging at a molecular level. In this study, we investigated the relationships between regional concentrations of metabolites (such as choline, creatine, myo-inositol, and N-acetyl-aspartate) and normal aging in 30 cognitively normal subjects (15 women and 15 men, age range 22–82, mean = 49.9 ± 18.3 years) using quantitative proton magnetic resonance spectroscopy. All MR scans were performed using a 3 T scanner. Point resolved spectroscopy was u...

  6. The aging mind: vascular health in normal cognitive aging.

    Science.gov (United States)

    Warsch, Jessica R L; Wright, Clinton B

    2010-10-01

    In spite of the breakneck speed at which understanding of the biological basis of the aging process has evolved, the important determinants of aging and longevity have yet to be uncovered. The preservation of cognitive functioning is an essential component of successful aging, and the ability to distinguish those who maintain cognitive health into advanced age from those who experience cognitive decline may influence public health efforts to prevent or delay the onset of cognitive impairment in old age. There is growing evidence implicating vascular risk factors and related subclinical cerebrovascular damage in cognitive impairment and dementia, but Alzheimer's disease is highly prevalent in older populations, and the role of inflammation in vascular and neurodegenerative processes is poorly understood. There is a growing need to examine the effects of these factors on normal cognitive aging. This brief survey of the literature reviews evidence of the roles of subclinical vascular brain damage and exposure to cerebrovascular risk factors in normal cognitive aging. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.

  7. Structural imaging measures of brain aging.

    Science.gov (United States)

    Lockhart, Samuel N; DeCarli, Charles

    2014-09-01

    During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

  8. Brain aging and therapeutic interventions

    DEFF Research Database (Denmark)

    This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic...

  9. Neuronal function in male Sprague Dawley rats during normal ageing

    African Journals Online (AJOL)

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic ...

  10. Nutrients, Microglia Aging, and Brain Aging

    Directory of Open Access Journals (Sweden)

    Zhou Wu

    2016-01-01

    Full Text Available As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  11. Nutrients, Microglia Aging, and Brain Aging.

    Science.gov (United States)

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  12. Diffuse brain damage in normal tension glaucoma.

    Science.gov (United States)

    Giorgio, Antonio; Zhang, Jian; Costantino, Francesco; De Stefano, Nicola; Frezzotti, Paolo

    2018-01-01

    Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Neurogenesis in the aging brain.

    Science.gov (United States)

    Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

    2017-10-01

    Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Aging, Brain Size, and IQ.

    Science.gov (United States)

    Bigler, Erin D.; And Others

    1995-01-01

    Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

  15. [Neuroethics (I): moral pathways in normal brain].

    Science.gov (United States)

    Álvaro-González, Luis C

    2014-03-01

    Morality is made of rules and values that guide human behavior. They barely change among different cultures. Social accomplishments are the result of moral development, due to a taint of fairness which pervades any human activity. The moral functions are the consequence of evolution and have their own specific neural circuits. To describe their appearance, starting and underlying mechanisms in the normal brain. Moral responses are basically homogeneous. They are linked to the emotional development, as much basic and individual (fear, wrath) as social (compassion, justice). Their emergence is the result of the emotional dichotomies pleasure/pain and reward/punishment, which lead to the basic moral dichotomy good/bad. For their working it is required the running of the prefrontal cortex (ventromedian and dorsolateral), the anterior cingular cortex and the superior temporal sulcus, that asses and elaborate and utilitarian moral response; and also the insula, the amygdale and the hypothalamus, that perform a quicker and emotionally rooted response. In addition, the mirror neuronal system (fronto-parietal) enables motor learning and empathy, linking this factor to the theory of mind. Moral sense and its responses underlay the complex social development that humans have reached and enjoyed. Thus opens ways for improving benefits in human groups and individuals alike. In addition, the knowledge of the normal function of the moral circuits is permeating and influencing the many areas of neuroculture.

  16. Magnetic resonance imaging of normal and pathologic fetal brain.

    Science.gov (United States)

    Resta, M; Burdi, N; Medicamento, N

    1998-01-01

    A total of 78 pregnant patients who had previously been studied by ultrasound (US) underwent magnetic resonance (MRI) because of suspected fetal abnormality. The first 20 cases were performed using fetal curarization. Even in the 27 cases in which the MR examination concerned other body regions, a brain study was always performed to analyze the normal anatomy at different gestational ages. There is a brief discussion on normal MRI anatomy of the fetal brain. There were 45 studies that concerned central nervous system pathology, and the most frequent malformative and neoplastic disorders were revealed. A comparison between MRI and US is proposed for each. In conclusion, MRI can be regarded as a complementary method that can be helpful in the rare cases when the US diagnosis is doubtful.

  17. [Normal aging of frontal lobe functions].

    Science.gov (United States)

    Calso, Cristina; Besnard, Jérémy; Allain, Philippe

    2016-03-01

    Normal aging in individuals is often associated with morphological, metabolic and cognitive changes, which particularly concern the cerebral frontal regions. Starting from the "frontal lobe hypothesis of cognitive aging" (West, 1996), the present review is based on the neuroanatomical model developed by Stuss (2008), introducing four categories of frontal lobe functions: executive control, behavioural and emotional self-regulation and decision-making, energization and meta-cognitive functions. The selected studies only address the changes of one at least of these functions. The results suggest a deterioration of several cognitive frontal abilities in normal aging: flexibility, inhibition, planning, verbal fluency, implicit decision-making, second-order and affective theory of mind. Normal aging seems also to be characterised by a general reduction in processing speed observed during neuropsychological assessment (Salthouse, 1996). Nevertheless many cognitive functions remain preserved such as automatic or non-conscious inhibition, specific capacities of flexibility and first-order theory of mind. Therefore normal aging doesn't seem to be associated with a global cognitive decline but rather with a selective change in some frontal systems, conclusion which should be taken into account for designing caring programs in normal aging.

  18. Nutrients, Microglia Aging, and Brain Aging

    OpenAIRE

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and ...

  19. Autobiographical Memory in Normal Ageing and Dementia

    Directory of Open Access Journals (Sweden)

    Harvey J. Sagar

    1991-01-01

    Full Text Available Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

  20. Normal aging induces A1-like astrocyte reactivity.

    Science.gov (United States)

    Clarke, Laura E; Liddelow, Shane A; Chakraborty, Chandrani; Münch, Alexandra E; Heiman, Myriam; Barres, Ben A

    2018-02-20

    The decline of cognitive function occurs with aging, but the mechanisms responsible are unknown. Astrocytes instruct the formation, maturation, and elimination of synapses, and impairment of these functions has been implicated in many diseases. These findings raise the question of whether astrocyte dysfunction could contribute to cognitive decline in aging. We used the Bac-Trap method to perform RNA sequencing of astrocytes from different brain regions across the lifespan of the mouse. We found that astrocytes have region-specific transcriptional identities that change with age in a region-dependent manner. We validated our findings using fluorescence in situ hybridization and quantitative PCR. Detailed analysis of the differentially expressed genes in aging revealed that aged astrocytes take on a reactive phenotype of neuroinflammatory A1-like reactive astrocytes. Hippocampal and striatal astrocytes up-regulated a greater number of reactive astrocyte genes compared with cortical astrocytes. Moreover, aged brains formed many more A1 reactive astrocytes in response to the neuroinflammation inducer lipopolysaccharide. We found that the aging-induced up-regulation of reactive astrocyte genes was significantly reduced in mice lacking the microglial-secreted cytokines (IL-1α, TNF, and C1q) known to induce A1 reactive astrocyte formation, indicating that microglia promote astrocyte activation in aging. Since A1 reactive astrocytes lose the ability to carry out their normal functions, produce complement components, and release a toxic factor which kills neurons and oligodendrocytes, the aging-induced up-regulation of reactive genes by astrocytes could contribute to the cognitive decline in vulnerable brain regions in normal aging and contribute to the greater vulnerability of the aged brain to injury. Copyright © 2018 the Author(s). Published by PNAS.

  1. Brain trace elements and aging

    International Nuclear Information System (INIS)

    Hebbrecht, Geert; Maenhaut, Willy; Reuck, Jacques de

    1999-01-01

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process

  2. Brain computed tomography findings of aged schizophrenics

    International Nuclear Information System (INIS)

    Oomori, Masao; Koshino, Yoshifumi; Murata, Tetsuhito; Murata, Ichirou; Tani, Kazuhiko; Horie, Tan; Isaki, Kiminori

    1992-01-01

    Brain CT was performed in a total of 30 aged schizophrenic patients, consisting of 20 with no history of psychosurgery (lobotomy) and the other 10 lobotomized patients. The CT findings were compared with those from healthy aged persons. The group of schizophrenic patients had marked atrophy of the frontal lobe and dilatated Sylvian fissure as compared with the control group. There was no significant difference in ventricular factors between the two groups. These findings may have implications for the different mechanisms of the occurrence of atrophied brain surface and enlarged ventricle. The cerebral cortex involved in the occurrence of schizophrenia may be affected by aging-related cerebral atrophy, in addition to the morphological changes due to schizophrenia. Thus, schizophrenic cerebral atrophy was more noticeable than physiological aging-related atrophy. However, enlargement of the ventricle in the schizophrenic group progressed with aging in the same manner as that in the normal group. In comparing schizophrenic patients with or without a history of lobotomy, atrophy of the brain surface and enlargement of the ventricle were more marked in the lobotomized patients than the non-lobotomized patients. This confirmed that lobotomy, as well as surgical scar, is involved in the morphology of schizophrenic brain. (N.K.)

  3. Dendritic spine changes associated with normal aging.

    Science.gov (United States)

    Dickstein, D L; Weaver, C M; Luebke, J I; Hof, P R

    2013-10-22

    Given the rapid rate of population aging and the increased incidence of cognitive decline and neurodegenerative diseases with advanced age, it is important to ascertain the determinants that result in cognitive impairment. It is also important to note that much of the aged population exhibit 'successful' cognitive aging, in which cognitive impairment is minimal. One main goal of normal aging studies is to distinguish the neural changes that occur in unsuccessful (functionally impaired) subjects from those of successful (functionally unimpaired) subjects. In this review, we present some of the structural adaptations that neurons and spines undergo throughout normal aging and discuss their likely contributions to electrophysiological properties and cognition. Structural changes of neurons and dendritic spines during aging, and the functional consequences of such changes, remain poorly understood. Elucidating the structural and functional synaptic age-related changes that lead to cognitive impairment may lead to the development of drug treatments that can restore or protect neural circuits and mediate cognition and successful aging. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Age Effects on Cortical Thickness in Cognitively Normal Elderly Individuals

    Directory of Open Access Journals (Sweden)

    Sona Hurtz

    2014-07-01

    Full Text Available Background/Aims: Atrophy in both grey and white matter is found in normal aging. The prefrontal cortex and the frontal lobe white matter are thought to be the most affected regions. Our aim was to examine the effects of normal aging on cortical grey matter using a 3D quantitative cortical mapping method. Methods: We analyzed 1.5-tesla brain magnetic resonance imaging data from 44 cognitively normal elderly subjects using cortical pattern matching and cortical thickness analyses. Linear regression analysis was used to study the effect of age on cortical thickness. 3D map-wide correction for multiple comparisons was conducted with permutation analyses using a threshold of p Results: We found a significant negative association between age and cortical thickness in the right hemisphere (pcorrected = 0.009 and a trend level association in the left hemisphere (pcorrected = 0.081. Age-related changes were greatest in the sensorimotor, bilateral dorsal anterior cingulate and supplementary motor cortices, and the right posterior middle and inferior frontal gyri. Age effects greater in the medial than lateral visual association cortices were also seen bilaterally. Conclusion: Our novel method further validates that normal aging results in diffuse cortical thinning that is most pronounced in the frontal and visual association cortices.

  5. Effects of smoking on brain aging, 2

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Matsuzawa, Taiju; Fujiwara, Takehiko

    1985-01-01

    Brain atrophy during normal aging and its relation to chronic smoking was studied using quantitative volumetric measurements of computed tomography. Study was performed about 159 smokers and 194 non-smokers with no neurological abnormality nor focal abnormality in CT scans. Each pixel of head CT scans was computed and Brain Volume Index (BVI) was calculated. BVI showed a significant decrease in smokers compared to non-smokers in three age groups, 50-to-54, 55-to-59 (p < 0.001, both) and 65-to-69 (p < 0.05). A dose-response study in the male showed that BVI in smokers was significantly lower than that for non smokers. Mean BVI tended to decrease when the smoking index increased but the trend was not significant. The systolic blood pressure and serum triglycrides of smokers were significantly higher than non-smokers (p < 0.002 and p < 0.05). It was suggested that age-related brain atrophy was enhanced by chronic smoking. Previously we showed that cerebral blood flow (CBF) was significantly lower in smokers than in non-smokers. Then, we suggest the following hypothesis; smoking chronically advances atherosclerosis, both atherosclerosis and high blood pressure reduce CBF, reduced CBF accelerated the lose of neurons which finally renders the brain atrophic. (author)

  6. Nutrition, brain aging, and neurodegeneration

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases superimposed on a declining nervous system could enhance the motor and cognitive behavioral deficits that normally occur in senescence. It is likely that, in cases of severe deficits in memory or motor function, hospitalization and/or custodial car...

  7. Problems in CT diagnosis of the aging brain

    International Nuclear Information System (INIS)

    Kohlmeyer, K.

    1989-01-01

    The different methods of measuring the intracranial CSF spaces on CT images are described. The values obtained are demonstrated to separate the normal aging brain from the brain in senile dementia of Alzheimer's type. The CT criteria for the diagnosis of multiinfarctdementia are shown. The significance of CT studies in senile depression is discussed. The problem of vascular encephalopathy (leukoaraiosis) in normal aging of the brain and in dementia is considered in particular, and even the occurrence of intracranial space-occupying lesions and normal pressure hydrocephalus, as treatable causes of dementia and depression, are mentioned. The data and results of my own CT research on normal brain aging, dementia and depression are presented with reference to the literature. (orig.) [de

  8. Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.

    Science.gov (United States)

    Cole, James H; Franke, Katja

    2017-12-01

    The brain changes as we age and these changes are associated with functional deterioration and neurodegenerative disease. It is vital that we better understand individual differences in the brain ageing process; hence, techniques for making individualised predictions of brain ageing have been developed. We present evidence supporting the use of neuroimaging-based 'brain age' as a biomarker of an individual's brain health. Increasingly, research is showing how brain disease or poor physical health negatively impacts brain age. Importantly, recent evidence shows that having an 'older'-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. We discuss controversies surrounding brain age and highlight emerging trends such as the use of multimodality neuroimaging and the employment of 'deep learning' methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. [Dreams in normal and pathological aging].

    Science.gov (United States)

    Guénolé, Fabian; Marcaggi, Geoffrey; Baleyte, Jean-Marc; Garma, Lucile

    2010-06-01

    Although most of scientific knowledge in dream research is based on young adult studies, this article provides a review of the effects of normal and pathological aging on dream psychology. It starts with preliminary comments about epistemological and methodological principles of dream research, its singularities in aged persons, and the modifications of sleep physiology with age. The whole literature agrees that dream recall progressively decreases from the beginning of adulthood - not in old age - and that dream reports become less intense, perceptually and emotionally. This evolution occurs faster in men than women, with gender differences in the content of dreams. The chronological modifications could be explained partly by changes in lifestyle and attitude towards dreams in early adulthood, but mainly by modifications of sleep physiology, particularly the decrease and qualitative changes of rapid eye movement (REM) sleep. Dreams have usually little subjective importance in the mental life of aged persons. However, working with dreams can be a valuable tool for psychotherapy in the aged. According to the few existing data, patients suffering degenerative dementia dream much less than healthy aged persons. In Alzheimer's disease, this could be linked to the decrease of REM sleep, and atrophy of associative sensory areas of the cerebral cortex. Most studied aspects of dreaming in degenerative cognitive disorders are REM sleep behavior disorders, and nightmares induced by cholinesterase inhibitors. More studies are needed to better characterize the evolution of dreams with age, particularly studies performed in sleep laboratory.

  10. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  11. Executive dysfunction, brain aging, and political leadership.

    Science.gov (United States)

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

  12. Brain aging, Alzheimer's disease, and mitochondria

    Science.gov (United States)

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  13. Brain: normal variations and benign findings in fluorodeoxyglucose-PET/computed tomography imaging.

    Science.gov (United States)

    Berti, Valentina; Mosconi, Lisa; Pupi, Alberto

    2014-04-01

    Brain 18F-fluorodeoxyglucose (18F-FDG) PET allows the in vivo study of cerebral glucose metabolism, reflecting neuronal and synaptic activity. 18F-FDG-PET has been extensively used to detect metabolic alterations in several neurologic diseases compared with normal aging. However, healthy subjects have variants of 18F-FDG distribution, especially as associated with aging. This article focuses on 18F-FDG-PET findings in so-called normal brain aging, and in particular on metabolic differences occurring with aging and as a function of people’s gender. The effect of different substances, medications, and therapy procedures are discussed, as well as common artifacts.

  14. Confirming the diversity of the brain after normalization: an approach based on identity authentication.

    Directory of Open Access Journals (Sweden)

    Fanglin Chen

    Full Text Available During the development of neuroimaging, numerous analyses were performed to identify population differences, such as studies on age, gender, and diseases. Researchers first normalized the brain image and then identified features that represent key differences between groups. In these studies, the question of whether normalization (a pre-processing step widely used in neuroimaging studies reduces the diversity of brains was largely ignored. There are a few studies that identify the differences between individuals after normalization. In the current study, we analyzed brain diversity on an individual level, both qualitatively and quantitatively. The main idea was to utilize brain images for identity authentication. First, the brain images were normalized and registered. Then, a pixel-level matching method was developed to compute the identity difference between different images for matching. Finally, by analyzing the performance of the proposed brain recognition strategy, the individual differences in brain images were evaluated. Experimental results on a 150-subject database showed that the proposed approach could achieve a 100% identification ratio, which indicated distinct differences between individuals after normalization. Thus, the results proved that after the normalization stage, brain images retain their main distinguishing information and features. Based on this result, we suggest that diversity (individual differences should be considered when conducting group analysis, and that this approach may facilitate group pattern classification.

  15. Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

    Science.gov (United States)

    Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

    2017-10-01

    Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

  16. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...

  17. Aging of the Brain: How Can We Prevent It?

    Science.gov (United States)

    Jarvik, Lissy F.

    1988-01-01

    Contends distinction between normal and abnormal aging of the brain changes as data emerge which identify as pathology what had previously been considered the norm. Reviews research on effects of aging in twins begun in 1940s, focusing on facts related to intellectual decline, neuropsychological test performance relationship to dementia, and…

  18. Topographical Distribution of Arsenic, Manganese, and Selenium in the Normal Human Brain

    DEFF Research Database (Denmark)

    Larsen, Niels Agersnap; Pakkenberg, H.; Damsgaard, Else

    1979-01-01

    The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brains from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron......% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue....

  19. The relationship between memory complaints and age in normal aging

    Directory of Open Access Journals (Sweden)

    Thaís Bento Lima-Silva

    Full Text Available Abstract Normal aging can be characterized by a gradual decline in some cognitive functions, such as memory. Memory complaints are common among older adults, and may indicate depression, anxiety, or cognitive decline. Objectives: To investigate the association between memory complaints and age in cognitively unimpaired older adults, and the relationship between memory complaints and memory performance. Methods: Cognitive screening tests as well as memory complaint questionnaires validated for the Brazilian population were used: the Mini-Mental State Examination (MMSE, Geriatric Depression Scale (GDS, Memory Complaint Questionnaire (MAC-Q, Memory test of 18 pictures, Forward and Backward Digit Span (WAIS-III. Fifty seven regular members of the SESC social club participated (50 women, having a mean age of 71.4 years, and 4 to 8 years of education - 34 from 4 to 7 years and 23 with 8 years of education. Results: Results revealed no significant association between cognitive complaints and age or cognitive performance. Older participants in this sample did not show worse performance or a higher level of complaints. There was no significant association between age and GDS scores. Conclusions: The studied sample constitutes a particular group of older adults whose participation in activities may be protecting them from cognitive decline, thus highlighting the impact of lifestyle on cognitive performance during the aging process.

  20. Optimisation of brain SPET and portability of normal databases.

    Science.gov (United States)

    Barnden, Leighton R; Hatton, Rochelle L; Behin-Ain, Setayesh; Hutton, Brian F; Goble, Elizabeth A

    2004-03-01

    Use of a normal database in quantitative regional analysis of brain single-photon emission tomography (SPET) facilitates the detection of functional defects in individual or group studies by accounting for inter-subject variability. Different reconstruction methods and suboptimal attenuation and scatter correction methods can introduce additional variance that will adversely affect such analysis. Similarly, processing differences across different instruments and/or institutions may invalidate the use of external normal databases. The object of this study was to minimise additional variance by comparing reconstructions of a physical phantom with its numerical template so as to optimise processing parameters. Age- and gender-matched normal scans acquired on two different systems were compared using SPM99 after processing with both standard and optimised parameters. For three SPET systems we have optimised parameters for attenuation correction, lower window scatter subtraction, reconstructed pixel size and fanbeam focal length for both filtered back-projection (FBP) and iterative (OSEM) reconstruction. Both attenuation and scatter correction improved accuracy for all systems. For single-iteration Chang attenuation correction the optimum attenuation coefficient (mu) was 0.45-0.85 of the narrow beam value (Nmu) before, and 0.75-0.85 Nmu after, scatter subtraction. For accurately modelled OSEM attenuation correction, optimum mu was 0.6-0.9 Nmu before and 0.9-1.1 Nmu after scatter subtraction. FBP appeared to change in-plane voxel dimensions by about 2% and this was confirmed by line phantom measurements. Improvement in accuracy with scatter subtraction was most marked for the highest spatial resolution system. Optimised processing reduced but did not remove highly significant regional differences between normal databases acquired on two different SPET systems.

  1. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

  2. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

    1984-01-01

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  3. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

    Science.gov (United States)

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-06-01

    Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and

  5. Physical exercise alleviates debilities of normal aging and Alzheimer's disease.

    Science.gov (United States)

    Archer, T

    2011-04-01

    Both healthy aging and the pathologic incidence of disorders associated with aging involve an array of debilities. Physical exercise harnesses implicit and inherent biologic characteristics amenable to the putative interventional influences under clinical, institutional or laboratory conditions. The neurodegenerative and pathophysiologic progressions that constitute Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), normal aging, and different animal models of AD have shown the existence of several putative mechanisms. A large variety of moderating factors have demonstrated that the ever-proliferating plethora of neurotrophic factors, neurogenesis as observed through generality of expression and neuronal arborization. The insistent efficacy of brain vascular angiogenesis may delay also the comorbid incidence of depressive disorders with dementia pathology. The pathogenesis of aging may be contained by selective treatments: these diverse conditions, linked to the basis of the aging concept, have been shown, to greater or lesser extents, to respond to a variety of scheduled applications of physical exercise. The range of reports that provide accounts of the mechanisms mediating the positive progressive response to exercise intervention is far-ranging; these studies indicate that subtle changes at molecular, neuronal, vascular and epigenetic levels may exert notable consequence at functional expression and, perhaps most essentially, offer convincing expectancy of significant benefits. © 2010 John Wiley & Sons A/S.

  6. The Aging Prostate Is Never "Normal"

    DEFF Research Database (Denmark)

    Schlomm, Thorsten; Weischenfeldt, Joachim; Korbel, Jan

    2015-01-01

    We argue against the recently published statement that tumor-specific molecular alterations found in "normal" prostate tissue from cancer patients challenge focal therapy approaches that only target a visible cancer lesion and not the adjacent molecular field....

  7. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus

    Science.gov (United States)

    Fjell, Anders M.; McEvoy, Linda; Holland, Dominic; Dale, Anders M.; Walhovd, Kristine B

    2015-01-01

    What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer’s Disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology. PMID:24548606

  9. Structural brain changes in aging: courses, causes and cognitive consequences.

    Science.gov (United States)

    Fjell, Anders M; Walhovd, Kristine B

    2010-01-01

    The structure of the brain is constantly changing from birth throughout the lifetime, meaning that normal aging, free from dementia, is associated with structural brain changes. This paper reviews recent evidence from magnetic resonance imaging (MRI) studies about age-related changes in the brain. The main conclusions are that (1) the brain shrinks in volume and the ventricular system expands in healthy aging. However, the pattern of changes is highly heterogeneous, with the largest changes seen in the frontal and temporal cortex, and in the putamen, thalamus, and accumbens. With modern approaches to analysis of MRI data, changes in cortical thickness and subcortical volume can be tracked over periods as short as one year, with annual reductions of between 0.5% and 1.0% in most brain areas. (2) The volumetric brain reductions in healthy aging are likely only to a minor extent related to neuronal loss. Rather, shrinkage of neurons, reductions of synaptic spines, and lower numbers of synapses probably account for the reductions in grey matter. In addition, the length of myelinated axons is greatly reduced, up to almost 50%. (3) Reductions in specific cognitive abilities--for instance processing speed, executive functions, and episodic memory--are seen in healthy aging. Such reductions are to a substantial degree mediated by neuroanatomical changes, meaning that between 25% and 100% of the differences between young and old participants in selected cognitive functions can be explained by group differences in structural brain characteristics.

  10. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo [Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Jae Sung [Seoul national University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5{+-}3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis.

  11. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo; Lee, Jae Sung

    2002-01-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5±3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis

  12. Selection of appropriate template for spatial normalization of brain images: tensor based morphometry

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Lee, Dong Soo; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul

    2004-01-01

    Although there have been remarkable advances in spatial normalization techniques, the differences in the shape of the hemispheres and the sulcal pattern of brains relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques. T1 SPGR MR images in 16 elderly male normal volunteers (>55 y. mean age: = 61.8 ± 3.5 y) were spatially normalized onto the age/gender specific Korean templates, and the Caucasian MNI template and the extent of the deformations were compared. These particular subjects were never included in the development of the templates. First , the images were matched into the templates using an affine transformation to eliminate the global difference between the templates and source images. Second the affine registration was followed by an estimation of nonlinear deformation. Determinants of the Jacobian matrices of the nonlinear deformation were then calculated for every voxel to estimate the regional volume change during the nonlinear transformation Jacobian determinant images highlighted the great magnitude of the relative local volume changes obtained when the elderly brains were spatially normalized onto the young/midlife male or female templates. They reflect the enlargement of CSF space in the lateral ventricles, sylvian fissures and cisterna magna, and the shrinkage of the cortex noted mainly in frontal, insular and lateral temporal cortexes, and the cerebellums in the aged brains. In the Jacobian determinant images, a regional shrinkage of the brain in the left middle prefrontal cortex was observed in addition to the regional expansion in the ventricles and sylvian fissures, which may be due to the age differences between the template and source images. The regional anatomical difference between template and source images could impose an extreme deformation of the source images during the spatial normalization and therefore. Individual brains should be placed into the appropriate template

  13. Selection of appropriate template for spatial normalization of brain images: tensor based morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Lee, Dong Soo; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Although there have been remarkable advances in spatial normalization techniques, the differences in the shape of the hemispheres and the sulcal pattern of brains relative to age, gender, races, and diseases cannot be fully overcome by the nonlinear spatial normalization techniques. T1 SPGR MR images in 16 elderly male normal volunteers (>55 y. mean age: = 61.8 {+-} 3.5 y) were spatially normalized onto the age/gender specific Korean templates, and the Caucasian MNI template and the extent of the deformations were compared. These particular subjects were never included in the development of the templates. First , the images were matched into the templates using an affine transformation to eliminate the global difference between the templates and source images. Second the affine registration was followed by an estimation of nonlinear deformation. Determinants of the Jacobian matrices of the nonlinear deformation were then calculated for every voxel to estimate the regional volume change during the nonlinear transformation Jacobian determinant images highlighted the great magnitude of the relative local volume changes obtained when the elderly brains were spatially normalized onto the young/midlife male or female templates. They reflect the enlargement of CSF space in the lateral ventricles, sylvian fissures and cisterna magna, and the shrinkage of the cortex noted mainly in frontal, insular and lateral temporal cortexes, and the cerebellums in the aged brains. In the Jacobian determinant images, a regional shrinkage of the brain in the left middle prefrontal cortex was observed in addition to the regional expansion in the ventricles and sylvian fissures, which may be due to the age differences between the template and source images. The regional anatomical difference between template and source images could impose an extreme deformation of the source images during the spatial normalization and therefore. Individual brains should be placed into the appropriate

  14. Structural brain variation, age, and response time.

    Science.gov (United States)

    Haier, Richard J; Jung, Rex E; Yeo, Ronald A; Head, Kevin; Alkire, Michael T

    2005-06-01

    Response time (RT) generally slows with aging, but the contribution of structural brain changes to this slowing is unknown. We used voxel-based morphometry (VBM) to determine gray matter (GM) and white matter (WM) brain volumes in 9 middle-aged adults (38-58 years old) and 9 seniors (66-82 years old). We correlated brain volumes with RT assessed in both a simple visual stimulus-response task and a visual continuous recognition memory task. No GM correlations with simple RT were significant; there was one WM correlation in the right fusiform gyrus. In the memory task, faster RT was correlated (p BAs 19, 37, 46, 9, 8, 6, 13, 10, 41, and 7). The results suggest that individual differences in specific brain structure volumes should be considered as potential moderating factors in cognitive brain imaging studies.

  15. Prenatal magnetic resonance imaging: brain normal linear biometric values below 24 gestational weeks

    Energy Technology Data Exchange (ETDEWEB)

    Parazzini, C.; Righini, A.; Triulzi, F. [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); Rustico, M. [Children' s Hospital ' ' V. Buzzi' ' , Department of Obstetrics and Gynecology, Milan (Italy); Consonni, D. [Fondazione IRCCS Ospedale Maggiore Policlinico, Unit of Epidemiology, Milan (Italy)

    2008-10-15

    Prenatal magnetic resonance (MR) imaging is currently used to measure quantitative data concerning brain structural development. At present, morphometric MR imaging studies have been focused mostly on the third trimester of gestational age. However, in many countries, because of legal restriction on abortion timing, the majority of MR imaging fetal examination has to be carried out during the last part of the second trimester of pregnancy (i.e., before the 24th week of gestation). Accurate and reliable normative data of the brain between 20 and 24 weeks of gestation is not available. This report provides easy and practical parametric support to assess those normative data. From a database of 1,200 fetal MR imaging studies, we retrospectively selected 84 studies of the brain of fetuses aged 20-24 weeks of gestation that resulted normal on clinical and radiological follow-up. Fetuses with proved or suspected infections, twin pregnancy, and fetuses of mothers affected by pathology that might have influenced fetal growth were excluded. Linear biometrical measurements of the main cerebral structures were obtained by three experienced pediatric neuroradiologists. A substantial interobserver agreement for each measurements was reached, and normative data with median, maximum, and minimum value were obtained for brain structures. The knowledge of a range of normality and interindividual variability of linear biometrical values for the developing brain between 20th and 24th weeks of gestation may be valuable in assessing normal brain development in clinical settings. (orig.)

  16. Effects of smoking on brain aging, 1

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Matsuzawa, Taiju; Yamaguchi, Tatsuo; Fujiwara, Takehiko; Seo, Shinya; Sasaki, Yuichiro.

    1985-01-01

    The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects from 25 to 85 years old were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. A hundred and twentyfive subjects who had no abnormalities in neurological examinations nor in CT scan, were divided into two groups smokers (48) and non-smokers (77). Those who had a smoking index (Number of cigarettes/day) x (years of smoking history)>200 were designated as smokers. The mean smoking index of smokers was 697. sixty-five of the 77 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 16. Increased reduction of CBF with advancing age was clearly observed. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF 15% lower in smokers, p<0.001). Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduced CBF. Age dependent decrease of CBF was deteriorated by chronic smoking. Then, chronic smoking was suggested to be a risk factor for brain aging. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels. (author)

  17. Normal versus Pathological Aging: Knowledge of Family Practice Residents.

    Science.gov (United States)

    Beall, S. Colleen; And Others

    1996-01-01

    Family physicians may lack discriminatory ability to differentiate normal aging form disease states. To assess such ability, 53 aging-related indicators or symptoms were presented to 65 physicians in 3 family practice residency programs. Respondents classified each symptom as normal aging or disease. On average, residents classified 73.4% of…

  18. Normal feline brain: clinical anatomy using magnetic resonance imaging.

    Science.gov (United States)

    Mogicato, G; Conchou, F; Layssol-Lamour, C; Raharison, F; Sautet, J

    2012-04-01

    The purpose of this study was to provide a clinical anatomy atlas of the feline brain using magnetic resonance imaging (MRI). Brains of twelve normal cats were imaged using a 1.5 T magnetic resonance unit and an inversion/recovery sequence (T1). Fourteen relevant MRI sections were chosen in transverse, dorsal, median and sagittal planes. Anatomic structures were identified and labelled using anatomical texts and Nomina Anatomica Veterinaria, sectioned specimen heads, and previously published articles. The MRI sections were stained according to the major embryological and anatomical subdivisions of the brain. The relevant anatomical structures seen on MRI will assist clinicians to better understand MR images and to relate this neuro-anatomy to clinical signs. © 2011 Blackwell Verlag GmbH.

  19. MRI of the normal brain from early childhood to middle age. Pt. 1. Appearances on T2- and proton density-weighted images and occurrence of incidental high-signal foci

    International Nuclear Information System (INIS)

    Autti, T.; Raininko, R.; Vanhanen, S.L.; Kallio, M.; Santavuori, P.

    1994-01-01

    The magnetic resonance images of 67 healthy subjects aged 4-50 years were studied for differences in general signal intensity between the different brain structures, the frequency of focal intensity changes in the brain, and variations in size of the cerebrospinal fluid (CSF) spaces. In adults over 25 years of age the thalamus gave lower signal than the putamen or caudate nucleus. Definite periventricular high signal was found in the white matter of one third of subjects of all ages. Small (< 5 mm in diameter) high signal foci were found in the cerebral white matter on T2-weighted images in 27 % of subjects (20 % of healthy children and adolescents and 34 % of adults). They gave high signal on both short and long echoes in 11 % of children and adolescents and in 22 % of adults; 51 % of all foci gave high signal with both echoes. This does not support the hypothesis that they are caused mainly by enlarged Virchow-Robin spaces. Of the high signal foci on T2-weighted images, 86 % were in watershead areas. Two foci were found in one subject in the periventricular watershed area (beside the tips of the frontal horns) and they were never seen in the other deep white matter regions. In healthy, relatively young subjects with no known risk factors, high signal foci other than Virchow-Robin spaces, were common; neither their prevalence nor their number correlated with age in this series. A few slightly large sulci were found in some adults. (orig.)

  20. Life and death of neurons in the aging brain

    Science.gov (United States)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  1. BrainAGE score indicates accelerated brain aging in schizophrenia, but not bipolar disorder.

    Science.gov (United States)

    Nenadić, Igor; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

    2017-08-30

    BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  2. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  3. Cardiovascular and hemodynamic contribution to brain aging

    NARCIS (Netherlands)

    Sabayan, Behnam

    2014-01-01

    In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is

  4. Changes in brain CT with aging

    International Nuclear Information System (INIS)

    Hiraiwa, Mikio; Abe, Toshiaki; Nonaka, Chizuru

    1983-01-01

    We have devised a new method for the objective evaluation of brain CT, a two-dimensional measurement: Two-dimensional measurement is based not on the developed films, but on treating raw data from magnetic tape. On the basis of our application of this method, we have discussed the changes in brain CT with aging. 135 patients, 72 males and 63 females, aged from 10 days to 78 years old, were subjected. The intracranial area showed a significant increase under 2 years old, but no marked changes after 3 years of age. The brain area increased under 2 years of age, and decreased after one's forties. The ventricular area showed no significant changes until the forties, but gradually increased thereafter. The bifrontal fluid-collection area was prominent in infancy, was almost invisible between 3 and 50 years of age and thereafter grew larger. For a relative comparison of brain CT scans with different intracranial areas, we devised three indices; BAI (brain-area index; brain area x 100/intracranial area), VAI (ventricular-area index; ventricular area x 100/intracranial area), and BFCI (bifrontal fluid-collection-area index; bifrontal fluid-collection area x 100/intracranial area). The BAI was low in infancy (under 95), was 96-97 between 3 and 50 years of age, and slowly decreased thereafter (88 in seventies). The VAI was under 2 until 50 years of age and gradually increased thereafter. The BFCI was high (over 3) in infancy and 0.2-0.4 between 3 and 50 years of age, and slowly increased thereafter. (J.P.N.)

  5. Social cognition in normal and pathological aging.

    Science.gov (United States)

    Fortier, Jonathan; Besnard, Jérémy; Allain, Philippe

    2016-12-01

    The concept of social cognition refers to a set of skills and to emotional and social experiences regulating relationships between individuals. This concept is appropriate in order to help us to explain individual human behaviours and behaviours in groups. Social cognition involves social knowledge, perception and processing of social cues, and the representation of mental states. The concept of social cognition thus refers to a multitude of skills. This paper stops on several of them, namely theory of mind, empathy, moral reasoning, emotional processing and emotional regulation. We propose a conceptual approach to each of these skills also stopping on their cerebral underpinnings. We also make an inventory of knowledge about the effects of age and neurodegenerative diseases on social cognition.

  6. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

  7. Normalization of Reverse Transcription Quantitative PCR Data During Ageing in Distinct Cerebral Structures.

    Science.gov (United States)

    Bruckert, G; Vivien, D; Docagne, F; Roussel, B D

    2016-04-01

    Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a routine method in many laboratories. Normalization of data from experimental conditions is critical for data processing and is usually achieved by the use of a single reference gene. Nevertheless, as pointed by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, several reference genes should be used for reliable normalization. Ageing is a physiological process that results in a decline of many expressed genes. Reliable normalization of RT-qPCR data becomes crucial when studying ageing. Here, we propose a RT-qPCR study from four mouse brain regions (cortex, hippocampus, striatum and cerebellum) at different ages (from 8 weeks to 22 months) in which we studied the expression of nine commonly used reference genes. With the use of two different algorithms, we found that all brain structures need at least two genes for a good normalization step. We propose specific pairs of gene for efficient data normalization in the four brain regions studied. These results underline the importance of reliable reference genes for specific brain regions in ageing.

  8. Structural MRI markers of brain aging early after ischemic stroke.

    Science.gov (United States)

    Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

    2017-07-11

    To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  9. Preliminary study of normal changes in brain white matter during childhood with diffusion tensor imaging

    International Nuclear Information System (INIS)

    Xiao Jiangxi; Guo Xuemei; Xie Sheng; Wang Xiaoying; Jiang Xuexiang

    2005-01-01

    Objective: To study the normal changes in brain white matter during childhood by analyzing the anisotropy of different regions and different age groups with diffusion tensor imaging (DTI). Methods: DTI was performed in 89 children (age range from 2 days to 18 years) without brain abnormalities, and the data measured in fractional anisotropy (FA) maps were analyzed statistically. Children less than 6 months were ranged to group 1, 6-12 months to group 2, 1-3 years to group 3, 3-5 years to group 4, 5-8 years to group 5, 8-12 years to group 6, 12-18 years to group 7. Results: (1) There were significant differences in anisotropy (FA values) among different regions of white matter in brain. In group 7, the FA value of corpus callosum was 0.826 ± 0.039, middle cerebellar peduncle 0.678 ± 0.043, frontal white matter 0.489 ± 0.033. (2) The anisotropy among different age group was statistically different, P<0.05. (3) The anisotropy of white matter increased with the increasing of age, and FA values showed positively exponentially correlations with age. Conclusion: DTI shows the structure of white matters in vivo, with which normal changes in brain during childhood can be evaluated. (authors)

  10. Accelerated aging syndromes, are they relevant to normal human aging?

    OpenAIRE

    Dreesen, Oliver; Stewart, Colin L.

    2011-01-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? ...

  11. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  12. EFFECTS OF BRAIN AGE TO INCREASE COGNITIVE FUNCTION IN ELDERLY

    Directory of Open Access Journals (Sweden)

    Achdiat Agoes

    2016-07-01

    Full Text Available Background. Among the elderly cognitive impairment is the biggest cause of the inability to perform normal daily activities, and also the most common reasons that lead to dependence on others to take care of their self. The concept of cognitive (from Latin cognosere, to know or to recognize refers to the ability to process information, applying knowledge, and change the trend. cognitive function of the elderly can be optimized through a variety of ways, one of that way is the brain training game (Brain Age. The game was created specifically to train the cognitive function of elderly. Objective. We determine the effect of brain training game (Brain Age to the improvement of cognitive function in the elderly in Malang. Methods. The design study is Quasi-experimental pretest-posttest approach, the treatment and control groups, and the sampling is done with purposive sampling to obtain the 20 respondents. Data collection instrument in this study are in general cognitive tests by using a measuring instrument MMSE. Results. Mann-Whitney test showed p value 0.000 <α 0.05. Conclusion. The conclusion from this study is that there is the effect of therapy brain training game (Brain Age on increasing cognitive function of elderly in Malang.

  13. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    Directory of Open Access Journals (Sweden)

    Simon Ducharme

    2015-12-01

    Full Text Available This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753 from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015 [1].

  14. Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

    Science.gov (United States)

    Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

    2008-01-01

    Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

  15. The Impact of Traumatic Brain Injury on the Aging Brain.

    Science.gov (United States)

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident.

  16. A Network Flow-based Analysis of Cognitive Reserve in Normal Ageing and Alzheimer's Disease.

    Science.gov (United States)

    Wook Yoo, Sang; Han, Cheol E; Shin, Joseph S; Won Seo, Sang; Na, Duk L; Kaiser, Marcus; Jeong, Yong; Seong, Joon-Kyung

    2015-05-20

    Cognitive reserve is the ability to sustain cognitive function even with a certain amount of brain damages. Here we investigate the neural compensation mechanism of cognitive reserve from the perspective of structural brain connectivity. Our goal was to show that normal people with high education levels (i.e., cognitive reserve) maintain abundant pathways connecting any two brain regions, providing better compensation or resilience after brain damage. Accordingly, patients with high education levels show more deterioration in structural brain connectivity than those with low education levels before symptoms of Alzheimer's disease (AD) become apparent. To test this hypothesis, we use network flow measuring the number of alternative paths between two brain regions in the brain network. The experimental results show that for normal aging, education strengthens network reliability, as measured through flow values, in a subnetwork centered at the supramarginal gyrus. For AD, a subnetwork centered at the left middle frontal gyrus shows a negative correlation between flow and education, which implies more collapse in structural brain connectivity for highly educated patients. We conclude that cognitive reserve may come from the ability of network reorganization to secure the information flow within the brain network, therefore making it more resistant to disease progress.

  17. Metabolic Imaging of Breast Cancer and the Normal Brain

    DEFF Research Database (Denmark)

    Asghar Butt, Sadia

    number of exciting possibilities for medical application, including early detection of disease. Such early detection allows for personalized treatment, which may increase the chances for a successful outcome. This PhD thesis is based on experimental studies on the cellular metabolism using MRS in two......) of hyperpolarized substrates enables the visualization, characterization, and quantification of biological processes taking without perturbing them. Biologic processes can, thus, be studied in their own physiologically authentic environment. This ability to measure fine metabolic changes opens up an incredible...... biological systems - breast cancer and normal brain. Breast cancer metabolism was longitudinally monitored in a mouse model using MRS of hyperpolirized pyruvate. The results demonstrated that we could monitor the changes in metabolism with increasing disease severity. The normal cerebral metabolism of α...

  18. Metabolic Imaging of Breast Cancer and the Normal Brain

    DEFF Research Database (Denmark)

    Asghar Butt, Sadia

    biological systems - breast cancer and normal brain. Breast cancer metabolism was longitudinally monitored in a mouse model using MRS of hyperpolirized pyruvate. The results demonstrated that we could monitor the changes in metabolism with increasing disease severity. The normal cerebral metabolism of α......Cellular metabolism is a set of biochemical reactions that happen in living organisms to maintain life. Enzymes act as catalysts and allow these reactions to proceed quickly and efficiently in order to maintain the cellular function and reproduction. Metabolic Magnetic Resonance Spectroscopy (MRS......) of hyperpolarized substrates enables the visualization, characterization, and quantification of biological processes taking without perturbing them. Biologic processes can, thus, be studied in their own physiologically authentic environment. This ability to measure fine metabolic changes opens up an incredible...

  19. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    International Nuclear Information System (INIS)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei

    2008-01-01

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6±5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  20. Cellular senescence and the aging brain.

    Science.gov (United States)

    Chinta, Shankar J; Woods, Georgia; Rane, Anand; Demaria, Marco; Campisi, Judith; Andersen, Julie K

    2015-08-01

    Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

    Directory of Open Access Journals (Sweden)

    Alexei A Podtelezhnikov

    Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age, Alz (Alzheimer, Inflame (inflammation, and NdStress (neurodegenerative stress. BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.

  2. Two hands, one brain, and aging.

    Science.gov (United States)

    Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

    2017-04-01

    Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  4. Knowledge of Normal versus Pathological Memory Aging among Police Officers

    Science.gov (United States)

    Hawley, Karri S.; Garrity, April W.; Cherry, Katie E.

    2005-01-01

    The authors examined police officers' knowledge of memory changes in adulthood utilizing the Knowledge of Memory Aging Questionnaire (KMAQ). The KMAQ is a 28-item true/false questionnaire that covers a broad range of topics related to normal memory aging due to maturational processes and pathological memory aging, such as adult dementia. Results…

  5. Nutrition for the ageing brain: Towards evidence for an optimal diet

    NARCIS (Netherlands)

    Vauzour, David; Camprubi-Robles, Maria; Miquel-Kergoat, Sophie; Andres-Lacueva, Cristina; Bánáti, Diána; Barberger-Gateau, Pascale; Bowman, Gene L.; Caberlotto, Laura; Clarke, Robert; Hogervorst, Eef; Kiliaan, Amanda J.; Lucca, Ugo; Manach, Claudine; Minihane, Anne-Marie; Mitchell, Ellen Siobhan; Perneczky, Robert; Perry, Hugh; Roussel, Anne-Marie; Schuermans, Jeroen; Sijben, John; Spencer, Jeremy P.E.; Thuret, Sandrine; De Rest, Van Ondine; Vandewoude, Maurits; Wesnes, Keith; Williams, Robert J.; Williams, Robin S.B.; Ramirez, Maria

    2017-01-01

    As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is

  6. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2013-12-01

    Full Text Available Aging alters brain structure and function and diabetes mellitus (DM may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs. The Brain Age Gap Estimation (i.e., BrainAGE score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM completed an MRI at 3T, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001, whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034, whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor (TNFα levels, lower verbal fluency scores and more severe depression. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019 and increased fasting blood glucose levels (r = 0.34, p = 0.025. In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.

  7. Quantifying the brain's sheet structure with normalized convolution.

    Science.gov (United States)

    Tax, Chantal M W; Westin, Carl-Fredrik; Dela Haije, Tom; Fuster, Andrea; Viergever, Max A; Calabrese, Evan; Florack, Luc; Leemans, Alexander

    2017-07-01

    The hypothesis that brain pathways form 2D sheet-like structures layered in 3D as "pages of a book" has been a topic of debate in the recent literature. This hypothesis was mainly supported by a qualitative evaluation of "path neighborhoods" reconstructed with diffusion MRI (dMRI) tractography. Notwithstanding the potentially important implications of the sheet structure hypothesis for our understanding of brain structure and development, it is still considered controversial by many for lack of quantitative analysis. A means to quantify sheet structure is therefore necessary to reliably investigate its occurrence in the brain. Previous work has proposed the Lie bracket as a quantitative indicator of sheet structure, which could be computed by reconstructing path neighborhoods from the peak orientations of dMRI orientation density functions. Robust estimation of the Lie bracket, however, is challenging due to high noise levels and missing peak orientations. We propose a novel method to estimate the Lie bracket that does not involve the reconstruction of path neighborhoods with tractography. This method requires the computation of derivatives of the fiber peak orientations, for which we adopt an approach called normalized convolution. With simulations and experimental data we show that the new approach is more robust with respect to missing peaks and noise. We also demonstrate that the method is able to quantify to what extent sheet structure is supported for dMRI data of different species, acquired with different scanners, diffusion weightings, dMRI sampling schemes, and spatial resolutions. The proposed method can also be used with directional data derived from other techniques than dMRI, which will facilitate further validation of the existence of sheet structure. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Different methods of measuring ADC values in normal human brain

    International Nuclear Information System (INIS)

    Wei Youping; Sheng Junkang; Zhang Caiyuan

    2009-01-01

    Objective: To investigate better method of measuring ADC values of normal brain, and provide reference for further research. Methods: Twenty healthy people's MR imaging were reviewed. All of them underwent routine MRI scans and echo-planar diffusion-weighted imaging (DWI), and ADC maps were reconstructed on work station. Six regions of interest (ROI) were selected for each object, the mean ADC values were obtained for each position on DWI and ADC maps respectively. Results: On the anisotropic DWI map calculated in the hypothalamus, ADC M , ADC P , ADC S values were no significant difference (P>0.05), in the frontal white matter and internal capsule hindlimb, there was a significant difference (P ave value exist significant difference to direct measurement on the anisotropic (isotropic) ADC map (P<0.001). Conclusion: Diffusion of water in the frontal white matter and internal capsule are anisotropic, but it is isotropic in the hypothalamus; different quantitative methods of diffusion measurement of 4ADC values have significant difference, but ADC values calculated through the DWI map is more accurate, quantitative diffusion study of brain tissue should also consider the diffusion measurement method. (authors)

  9. Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus

    International Nuclear Information System (INIS)

    Freimann, Florian Baptist; Sprung, Christian; Streitberger, Kaspar-Josche; Klatt, Dieter; Sack, Ingolf; Lin, Kui; McLaughlin, Joyce; Braun, Juergen

    2012-01-01

    Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 ± 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters μ and α, related to the inherent rigidity and topology of the mechanical network of brain tissue. The viscoelastic parameters μ and α were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, α increased after shunt placement (P < 0.001) to almost normal values whereas μ remained symptomatically low. The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded. (orig.)

  10. Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Freimann, Florian Baptist; Sprung, Christian [Charite - University Medicine Berlin, Campus Virchow-Klinikum, Neurosurgical Department, Berlin (Germany); Streitberger, Kaspar-Josche; Klatt, Dieter; Sack, Ingolf [Charite - University Medicine Berlin, Campus Charite Mitte, Department of Radiology, Berlin (Germany); Lin, Kui; McLaughlin, Joyce [Rensselaer Polytechnic Institute, Mathematics Department, Troy, NY (United States); Braun, Juergen [Charite - University Medicine Campus Benjamin Franklin, Institute of Medical Informatics, Berlin (Germany)

    2012-03-15

    Normal pressure hydrocephalus (NPH) represents a chronic neurological disorder with increasing incidence. The symptoms of NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid. However, the pathogenesis of NPH is not yet fully elucidated, and the clinical response of shunt treatment is hard to predict. According to current theories of NPH, altered mechanical properties of brain tissue seem to play an important role. Magnetic resonance elastography (MRE) is a unique method for measuring in vivo brain mechanics. In this study cerebral MRE was applied to test the viscoelastic properties of the brain in 20 patients with primary (N = 14) and secondary (N = 6) NPH prior and after (91 {+-} 16 days) shunt placement. Viscoelastic parameters were derived from the complex modulus according to the rheological springpot model. This model provided two independent parameters {mu} and {alpha}, related to the inherent rigidity and topology of the mechanical network of brain tissue. The viscoelastic parameters {mu} and {alpha} were found to be decreased with -25% and -10%, respectively, compared to age-matched controls (P < 0.001). Interestingly, {alpha} increased after shunt placement (P < 0.001) to almost normal values whereas {mu} remained symptomatically low. The results indicate the fundamental role of altered viscoelastic properties of brain tissue during disease progression and tissue repair in NPH. Clinical improvement in NPH is associated with an increasing complexity of the mechanical network whose inherent strength, however, remains degraded. (orig.)

  11. CT attenuation in normal aging and Alzheimer's disease

    International Nuclear Information System (INIS)

    Kim, W.S.; Pearlson, G.D.; Goldfinger, A.D.; Tune, L.E.; Heyler, G.

    1986-01-01

    113 screened normal volunteers aged 18-85 and 50 elderly demented individuals meeting NINCDS/ADRDA criteria for probable senile dementia of the Alzheimer type, (SDAT), received a non-contrast x-CT head scan on a single 512x512 matrix Siemens Somatom DR3 Scanner. Scanning parameters (KV,MA) were kept constant, and the authors used a specially designed head holder to ensure a uniform scanning angle. Standard 8mm thick cuts, at zero degrees to the supra-orbito-meatal line, were taken through the entire brain. A ''phantom'' consisting of plastics of several different attenuation values was scanned before each patient as a reference to correct for any numerical drift in the scanner. Both patients and controls were scanned during the same sessions to eliminate possible systematic bias, and a single CT technologist carried out all scanning. Numerical CT data were collected on magnetic tape for analysis on a specially designed image processing system. Software was used to read CT density data from the 512x512 matrix scanner output tapes and to transfer the resulting image in standardized format to hard disk on the processing system. This system consists of a PDP-11-34 computer, linked to a Gould DeAnza IP-5000 image processors, hard disk system and tape drive. Once transferred to disk, images were rated blindly to subject identity or diagnosis by another 2 separate raters using a computer-linked cursor, and digitizer tablet. These numerical attenuation data from various anatomically defined regions of interest, (ROI's), were then corrected for head size using a regression model

  12. Microglia priming in the aging brain : Implications for neurodegeneration

    NARCIS (Netherlands)

    Darwin Arulseeli, Divya; Biber, Knut

    2016-01-01

    The primary aim of the thesis “Microglia priming in the aging brain: Implications for neurodegeneration” was to understand microglia phenotypes associated with brain aging and the potential mechanisms for this age-associated change. Microglia in the aging brain assume a hypersensitive

  13. Performance of brain-damaged, schizophrenic, and normal subjects on a visual searching task.

    Science.gov (United States)

    Goldstein, G; Kyc, F

    1978-06-01

    Goldstein, Rennick, Welch, and Shelly (1973) reported on a visual searching task that generated 94.1% correct classifications when comparing brain-damaged and normal subjects, and 79.4% correct classifications when comparing brain-damaged and psychiatric patients. In the present study, representing a partial cross-validation with some modification of the test procedure, comparisons were made between brain-damaged and schizophrenic, and brain-damaged and normal subjects. There were 92.5% correct classifications for the brain-damaged vs normal comparison, and 82.5% correct classifications for the brain-damaged vs schizophrenic comparison.

  14. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  15. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  16. Brain pathologies in extreme old age.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Jicha, Gregory A; Schmitt, Frederick A; Patel, Ela; Poon, Leonard W; Marla, Gearing; Green, Robert C; Davey, Adam; Johnson, Mary Ann; Jazwinski, S Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L; Kryscio, Richard J; Van Eldik, Linda J; Nelson, Peter T

    2016-01-01

    With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98-107) years overall. Alzheimer's disease pathology was not universal (62% with "moderate" or "frequent" neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  18. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi (Kyoto Prefectural Univ. of Medicine (Japan))

    1994-11-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author).

  19. Magnetic resonance imaging of neonatal brain. Assessment of normal and abnormal findings

    International Nuclear Information System (INIS)

    Hasegawa, Koh; Kadono, Naoko; Kawase, Shohji; Kihara, Minako; Matsuo, Yasutaka; Yoshioka, Hiroshi; Kinugasa, Akihiko; Sawada, Tadashi

    1994-01-01

    To establish the normal MRI appearance of the neonatal brain, magnetic resonance imaging (MRI) was performed on 124 neonates who admitted to our neonatal intensive care unit. Degree of myelination, ventricular size, width of the extracerebral space and focal lesion in the brain were evaluated to investigate the relationship between MRI findings of neonatal brain and the neurological prognosis. 85 neonates underwent MRI both at neonatal period and at the corrected age of one year. The change of abnormal MRI findings was evaluated. 19 neonates had abnormal neurological outcome on subsequent examinations. Delayed myelination, ventriculomegaly and large extracerebral space were seen in 13, 7 and 9 neonates respectively. 4, 3 and 5 neonates out of them showed abnormal neurological prognosis respectively. Of the 19 neonates with focal lesion in MRI, 2 had parenchymal hematoma in the brain, 2 had subdural hematoma, 5 had chronic hematoma following subependymal hemorrhage, 6 had cystic formation following subependymal hemorrhage, 2 had subcortical leukomalacia, one had periventricular leukomalacia and one had cyst in the parenchyma of cerebellum. 4 neonates of 19 with focal lesion in MRI showed abnormal development. Of the neonates who had abnormal neurological prognosis, 7 neonates showed no abnormal finding in MRI at neonatal period. 3 of them had mild mental retardation. MRI shows promise in the neonatal period. It facilitates recognition of abnormalities of neonatal brain and may be used to predict abnormal neurologic outcome. However physiological change in the brain of neonates, especially of premature neonates, should be considered on interpreting these findings. Awareness of developmental features should help to minimize misinterpretation of normal changes in the neonatal brain. (author)

  20. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons.

    Science.gov (United States)

    Donohue, Michael C; Sperling, Reisa A; Petersen, Ronald; Sun, Chung-Kai; Weiner, Michael W; Aisen, Paul S

    2017-06-13

    Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized z scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR-Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units). Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR-Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P normal cohort followed up for a median of 3.1 years suggest that elevation in baseline brain amyloid level, compared with normal brain

  1. Patterns of brain structural connectivity differentiate normal weight from overweight subjects.

    Science.gov (United States)

    Gupta, Arpana; Mayer, Emeran A; Sanmiguel, Claudia P; Van Horn, John D; Woodworth, Davis; Ellingson, Benjamin M; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S

    2015-01-01

    Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69

  2. Patterns of brain structural connectivity differentiate normal weight from overweight subjects

    Science.gov (United States)

    Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

    2015-01-01

    Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42

  3. Impact of Aging Brain Circuits on Cognition

    Science.gov (United States)

    Samson, Rachel D.; Barnes, Carol A.

    2013-01-01

    Brain networks that engage the hippocampus and prefrontal cortex are central for enabling effective interactions with our environment. Some of the cognitive processes that these structures mediate, such as encoding and retrieving episodic experience, wayfinding, working memory and attention are known to be altered across the lifespan. As illustrated by examples given below, there is remarkable consistency across species in the pattern of age-related neural and cognitive change observed in healthy humans and other animals. These include changes in cognitive operations that are known to be dependent on the hippocampus, as well as those requiring intact prefrontal cortical circuits. Certain cognitive constructs that reflect the function of these areas lend themselves to investigation across species allowing brain mechanisms at different levels of analysis to be studied in greater depth. PMID:23773059

  4. Brain metabolism in health, aging, and neurodegeneration.

    Science.gov (United States)

    Camandola, Simonetta; Mattson, Mark P

    2017-06-01

    Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  5. Increased brain-predicted aging in treated HIV disease.

    Science.gov (United States)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  6. Early radiation changes of normal dog brain following internal and external brain irradiation: A preliminary report

    International Nuclear Information System (INIS)

    Chin, H.; Maruyama, Y.; Markesbery, W.; Goldstein, S.; Wang, P.; Tibbs, P.; Young, B.; Feola, J.; Beach, L.

    1984-01-01

    To examine radiation-induced changes in the normal brain, internal or external radiation was given to normal dog brain. Seven medium-sized dogs were used in this study. Two dogs were controls and an ice-pick (plastic implant applicator) was placed in the right frontal lobe for about 5 hours but no irradiation. Two dogs underwent Cs-137 brain implantation for 4 and 5 hours, respectively using an ice-pick technique. Two dogs were given internal neutron irradiation using the same technique of intracerebral ice-pick brachytherapy. One dog received an external photon irradiation using 6-Mev Linear Accelerator. Postmortem microscopic examination was made to study the early cerebral changes to irradiation in three dogs: one control with no irradiation; one received intracerebral Cesium implantation; and one external photon irradiation. Vascular change was the most prominent microscopic finding. There were hemorrhage, endothelial proliferation and fibrinoid changes of small vessel wall. Most of the changes were localized in the white matter and the cortex remained intact. Details (CT, NMR and histological studies) are discussed

  7. Thermal dosimetry studies of ultrasonically induced hyperthermia in normal dog brain and in experimental brain tumors

    International Nuclear Information System (INIS)

    Britt, R.H.; Pounds, D.W.; Stuart, J.S.; Lyons, B.E.; Saxer, E.L.

    1984-01-01

    In a series of 16 acute experiments on pentobarbital anesthetized dogs, thermal distributions generated by ultrasonic heating using a 1 MHz PZT transducer were compared with intensity distributions mapped in a test tank. Relatively flat distributions from 1 to 3 cm have been mapped in normal dog brain using ''shaped'' intensity distributions generated from ultrasonic emission patterns which are formed by the interaction between compressional, transverse and flexural modes activated within the crystal. In contrast, these same intensity distributions generated marked temperature variations in 3 malignant brain tumors presumably due to variations in tumor blood flow. The results of this study suggest that a practical clinical system for uniform heating of large tumor volumes with varying volumes and geometries is not an achievable goal. The author's laboratory is developing a scanning ultrasonic rapid hyperthermia treatment system which will be able to sequentially heat small volume of tumor tissue either to temperatures which will sterilize tumor or to a more conventional thermal dose. Time-temperature studies of threshold for thermal damage in normal dog brain are currently in progress

  8. Normal aging modulates the neurotoxicity of mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  9. Age-related infra-tentorial brain atrophy on CT scan

    International Nuclear Information System (INIS)

    Kitani, Mitsuhiro; Kobayashi, Shotai; Yamaguchi, Shuhei; Okada, Kazunori; Murata, Akihiro; Tsunematsu, Tokugoro

    1985-01-01

    We had reported that the brain atrophy progressed significantly with advancing age using the two dimensional CT measurement by digitizer which was connected with personal computer. Using this method, we studied the age-related infra-tentrial brain atrophy in 67 normal subjects (14-90 years), and compared that with age-related supra-tentrial brain atrophy. There was a significant correlation between age and all indices [cranio-ventricular index (CVI), ventricular area index (VAI) and brain atrophy index (BAI)] in supratentrial brain. These indices did not correlated to the age in infra-tentrial brain (brainstem and cerebellum). Significant change of the brain atrophy occured above 60 years old was observed by BAI and VAI in supra-tentrial brain. There was a significant correlation between supra-tentrial brain atrophy index (BAI) and that of infratentrial brain. These results indicate that age-related brain atrophy might progress more slowly in brainstem and cerebellum than in cerebrum. (author)

  10. Phenotype of normal spirometry in an aging population.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

    2015-10-01

    In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

  11. Brain Age in Early Stages of Bipolar Disorders or Schizophrenia.

    Science.gov (United States)

    Hajek, Tomas; Franke, Katja; Kolenic, Marian; Capkova, Jana; Matejka, Martin; Propper, Lukas; Uher, Rudolf; Stopkova, Pavla; Novak, Tomas; Paus, Tomas; Kopecek, Miloslav; Spaniel, Filip; Alda, Martin

    2017-12-20

    The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

  12. TRAUMATIC BRAIN INJURY IN PEDIATRIC AGE GROUP

    Directory of Open Access Journals (Sweden)

    Hayagriva

    2015-11-01

    Full Text Available Traumatic brain injury is one of the major causes of morbidity and mortality in children. The anatomical features, physiological response to injury, neuronal development, and low myelination in children cause different clinical features compared to the adult traumatic brain injury. Our aim is to study the incidence, predisposing factors, clinical presentations, and outcome in pediatric head injuries. The patients included in this retrospective study are under the age of 14 years admitted in the Neurosurgery Department of King George Hospital, Visakhapatnam, which is a tertiary care centre. The study period is two years’ duration from 1.1.2013 to 31.12.2014. Data collected on the basis of history, physical examination, base line investigations, and the plain CT scan is all cases. The pediatric patients were 226 in total 1643 case of head injury cases. There were 64.6% (n=146 males and 35.4% (n=80 females. The age ranged from 12 days to 14 years. Fall from height was the commonest cause of head injury found in 48.6% (n=110 cases, road traffic accidents (RTA in 34.5% (n=78 and other causes 16.8% (n=38; 49 (21.68% patients had associated injuries. At 55.75% (n=126 cases mild head injury with GCS 13-15 was present and severe head injury with GCS less than 8 in 29 (12.8% patients. The 188 patients are treated conservatively, 38 patients underwent different neurosurgical procedures in which 5 patients died. CONCLUSION: Head injury in pediatric age group carries high risk of morbidity and mortality. Good outcome achieved by early diagnosis and referral from primary care centers to tertiary care centers.

  13. Age related changes in metabolite concentrations in the normal spinal cord.

    Directory of Open Access Journals (Sweden)

    Khaled Abdel-Aziz

    Full Text Available Magnetic resonance spectroscopy (MRS studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23-65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010 and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002 was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging.

  14. Neuroethics in the Age of Brain Projects.

    Science.gov (United States)

    Greely, Henry T; Ramos, Khara M; Grady, Christine

    2016-11-02

    Neuroscience advances have brought important ethical questions. The recent launch of two large brain projects, the United States BRAIN Initiative and the European Union Human Brain Project, should accelerate progress in understanding the brain. This article examines neuroethics in those two projects, as well as its exploration by other efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Cellular senescence in normal and premature lung aging.

    Science.gov (United States)

    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  16. Normal ventricular size and changes with age in pediatric groups on computed tomography

    International Nuclear Information System (INIS)

    Nakada, Yoshitaka; Nose, Tadao; Enomoto, Takao; Maki, Yutaka

    1980-01-01

    The purpose of this report is to determine the normal value of the ventricular size on CT, snd analyze its changes with age in normal pediatric group. Materials and Methods: We searched through our 240 normal pediatric CT film files, aged 4 months to 14 years. Scans were performed on Hitachi CT-II scanner, using 10 mm collimation. Results: 1. The width of the third ventricle showed the same value in all pediatric groups, the mean value of its being 4.8 mm (SD 1.3 mm). 2. Bicaudate cerebroventricular indexes of the anterior horns of lateral ventricles (interecarlate distance/transverse diameter of the brain x100) were 15.3 in infants under one year, 13.8 in the age of one year and 12.7 in the children over two years. The indexes were almost the same in old age group over the age of three years. 3. The upper limit of the normal inverse cella media index (minium width of cella media/transverse diameter of the brain x100) was 31. Therefore the cases with the index above this range can be diagnosed as hydrocephalic. 4. The shape of the anterior horns of lateral ventricles was Y-shaped in infants under one year. II-shaped (paralied shaped) in the age of 1 - 12 years, and again it was Y-shaped in the group over 12 years. 5. In the age group under one year, the temporal horns of the lateral ventricles were visualized in about 60% cases, while the figure decreased to 20% in the older group. (author)

  17. Brain Aging in the Oldest-Old

    Directory of Open Access Journals (Sweden)

    A. von Gunten

    2010-01-01

    Full Text Available Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs and senile plaques (SPs as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions

  18. The benefits of aging: cellular senescence in normal development.

    Science.gov (United States)

    Pérez-Garijo, Ainhoa; Steller, Herman

    2014-01-13

    Senescence is a form of cellular aging that limits the proliferative capacity of cells. Senescence can be triggered by different stress stimuli, such as DNA damage or oncogene activation. Two recent articles published in Cell have uncovered an unexpected role for cellular senescence during development, as a process that contributes to remodeling and patterning of the embryo. These findings are exciting and have important implications for the understanding of normal developmental and the evolutionary origin of senescence.

  19. Magnetic resonance elastography in normal human brain: preliminary study

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2007-01-01

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  20. Microstructure, length, and connection of limbic tracts in normal human brain development

    Directory of Open Access Journals (Sweden)

    Qiaowen eYu

    2014-08-01

    Full Text Available The cingulum and fornix play an important role in memory, attention, spatial orientation and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI and resting state functional MRI (rs-fMRI data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc, hippocampal part of the cingulum (cgh and fornix (fx were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2-year-old followed by a slow increase to 25-year-old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network (DMN was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with

  1. Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

    Science.gov (United States)

    Bischof, Gérard N; Park, Denise C

    2015-01-01

    This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

  2. Differential course of executive control changes during normal aging.

    Science.gov (United States)

    Treitz, Friederike H; Heyder, Katrin; Daum, Irene

    2007-07-01

    Normal aging has been associated with executive control deficits, but it is as yet unclear whether different executive subprocesses are differentially affected during the course of aging. The present study aimed to investigate age effects on a range of executive control subcomponents. Four consecutive age groups (20-30 years, 31-45 years, 46-60 years, 61-75 years), matched on present state IQ and mood, were compared on tasks of strategic memory processing, verbal fluency, reasoning, inhibition, task management, and self-rating of executive abilities. Deficits concerning the suppression of habitual and experimentally induced prepotent response tendencies and the ability to efficiently divide attention were observed in subjects over 60 years of age compared to the younger groups, while memory, verbal fluency, and reasoning were largely unaffected. Results suggest a sharp decline of executive function after age 60 and a differential course of different executive subcomponents across aging, adding further support to a multi-dimensional model of executive function.

  3. Development of normal fetal brain by MRI with a half-Fourier rapid acquisition with relaxation enhancement sequence

    International Nuclear Information System (INIS)

    Li Meilan; Liu Xuejun; Wang Jianhong; Zhao Cheng; Li Xiang

    2006-01-01

    Objective: To evaluate normal maturation of the fetal brain with half-Fourier rapid acquisition with relaxation enhancement (RARE) MRI. Methods: The normal brains of 25 fetuses of 12-38 weeks gestational age were examined in utero with half-Fourier RARE imaging. Gyrus maturation, gray and white matter differentiation, ventricle-to-brain diameter ratio, and subarachnoid space size were evaluated with respect to gestational age. Results: At 12-23 weeks, the brain had a smooth surface, and two or three layers were differentiated in the cerebral cortex. At 24-26 weeks, only a few shallow grooves were seen in the central sulcus, and three layers, including the immature cortex, intermediate zone, and germinal matrix, were differentiated in all fetuses. At 27-29 weeks, sulcus formation was observed in various regions of the brain parenchyma, and the germinal matrix became invisible. Sulcation was seen in the whole cerebral cortex from 30 weeks on. However, the cortex did not undergo infolding, and opercular formation was not seen before 33 weeks. At 23 weeks and earlier, the cerebral ventricles were large; thereafter, they gradually became smaller. The subarachnoid space overlying the cortical convexities was slightly dilated at all gestational ages, most markedly at 21-26 weeks. Conclusion: Changes in brain maturation proceed through stages in an orderly and predictable fashion and can be evaluated reliably with half-Fourier RARE MRI. (authors)

  4. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kurca, E.; Sivak, S.; Kucera, P.

    2006-01-01

    Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities. (orig.)

  5. Age-matched normal values and topographic maps for regional cerebral blood flow measurements by Xe-133 inhalation

    International Nuclear Information System (INIS)

    Matsuda, H.; Maeda, T.; Yamada, M.; Gui, L.X.; Tonami, N.; Hisada, K.

    1984-01-01

    The relationship between normal aging and regional cerebral blood flow (rCBF) computed as initial slope index (ISI) by Fourier method was investigated in 105 right-handed healthy volunteers (132 measurements) by Xe-133 inhalation method, and age-matched normal values were calculated. Mean brain ISI values showed significant negative correlation with advancing age (r . 0.70, p less than 0.001), and the regression line and its 95% confidence interval was Y . -0.32 (X - 19) + 63.5 +/- 11.2 (19 less than or equal to X less than or equal to 80). Regional ISI values also showed significant negative correlations for the entire brain (p less than 0.001). The regional reductions of ISI values with advancing age were significantly greater in the regional distribution of the middle cerebral arteries bilaterally, compared with regions in the distribution of the other arteries (p less than 0.05). Therefore, measured rCBF values for patients must be compared to age-matched normal values for mean hemispheric and each region examined. Two kinds of topographic maps, brain map showing rCBF compared to age-matched normal values and showing hemispheric differences were made by dividing patient's values by the 95% confidence limits for age-matched normal values and displaying laterality index calculated as follows, respectively. (formula; see text) These maps were useful for evaluating significantly decreased or increased regions and regional hemispheric differences

  6. High energy reactions in normal metabolism and ageing of animals

    International Nuclear Information System (INIS)

    Avdonina, E.N.; Nesmeyanov, N.

    1983-01-01

    Processes involving reactions on highly excited states are thought to be of great importance for normal metabolism and aging. Excess energy of the organism is transferred to result in the formation of highly excited states of macromolecules. UV, visible light or ionizing radiation created partially by the organism itself can change metabolic process rates. According to the authors, aging is associated with the defects of macromolecules owing to high energy processes. Gerontological changes in biological materials result from the elimination of low molecular weight molecules and from the formation of unsaturated compounds. Crosslinking of the compounds, accumulation of collagen and connective tissues, the energetic overload of the organism are listed as important features of aging. (V.N.)

  7. Hierarchical clustering of Alzheimer and 'normal' brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    International Nuclear Information System (INIS)

    Cutts, D.A.; Spyrou, N.M.

    2001-01-01

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element concentrations in the frontal lobe were determined for twenty six Alzheimer (15 male, 11 female) and twenty six 'normal' (8 male, 18 female) brain tissue samples. In the parietal lobe ten Alzheimer (2 male, 8 female) and ten 'normal' (8 male, 2 female) samples were taken along with ten Alzheimer (4 male, 6 female) and ten 'normal' (6 male, 4 female) from the occipital lobe. For the frontal lobe trace element concentrations were determined using proton induced X-ray emission (PIXE) analysis while in parietal and occipital regions instrumental neutron activation analysis (INAA) was used. Additionally eighteen Alzheimer (9 male, 9 female) and eighteen age matched 'normal' (8 male, 10 female) living subjects were examined using positron emission tomography (PET) in order to determine regional cerebral metabolic rates of glucose (rCMRGlu). The rCMRGlu of 36 regions of the brain was investigated including frontal, occipital and parietal lobes as in the trace element study. Hierarchical cluster analysis was applied to the trace element and glucose metabolism data to discover which variables in the resulting dendrograms displayed the most significant separation between Alzheimer and 'normal' subjects. (author)

  8. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  9. Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging.

    Science.gov (United States)

    Shamir, Lior; Long, Joe

    2016-01-01

    While cognition is clearly affected by aging, it is unclear whether the process of brain aging is driven solely by accumulation of environmental damage, or involves biological pathways. We applied quantitative image analysis to profile the alteration of brain tissues during aging. A dataset of 463 brain MRI images taken from a cohort of 416 subjects was analyzed using a large set of low-level numerical image content descriptors computed from the entire brain MRI images. The correlation between the numerical image content descriptors and the age was computed, and the alterations of the brain tissues during aging were quantified and profiled using machine learning. The comprehensive set of global image content descriptors provides high Pearson correlation of ~0.9822 with the chronological age, indicating that the machine learning analysis of global features is sensitive to the age of the subjects. Profiling of the predicted age shows several periods of mild changes, separated by shorter periods of more rapid alterations. The periods with the most rapid changes were around the age of 55, and around the age of 65. The results show that the process of brain aging of is not linear, and exhibit short periods of rapid aging separated by periods of milder change. These results are in agreement with patterns observed in cognitive decline, mental health status, and general human aging, suggesting that brain aging might not be driven solely by accumulation of environmental damage. Code and data used in the experiments are publicly available.

  10. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Huisman, Thierry A.G.M.; Kubik-Huch, Rahel; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, 8091 Zurich (Switzerland); Martin, Ernst [Department of Neuroradiology and Magnetic Resonance, University Children' s Hospital, 8091 Zurich (Switzerland)

    2002-08-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. (orig.)

  11. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development

    International Nuclear Information System (INIS)

    Huisman, Thierry A.G.M.; Kubik-Huch, Rahel; Marincek, Borut; Martin, Ernst

    2002-01-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality. (orig.)

  12. Fetal magnetic resonance imaging of the brain: technical considerations and normal brain development.

    Science.gov (United States)

    Huisman, Thierry A G M; Martin, Ernst; Kubik-Huch, Rahel; Marincek, Borut

    2002-08-01

    Fetal MRI examines non-invasively the unborn fetus. Ultrafast MRI sequences effectively suppress fetal motion. Multiple case reports and studies have shown that fetal MRI is particularly helpful in the evaluation of the central nervous system. The high contrast-to-noise ratio, the high spatial resolution, the multiplanar capabilities, the large field of view and the simultaneous visualisation of fetal and maternal structures have proven to be advantageous. Fetal MRI is particularly helpful in the evaluation of the normal and pathological development of the brain. Despite the fact that no side effects have been reported or are to be expected, the use of MRI during pregnancy is still limited to the second and third trimester of pregnancy. Magnetic resonance imaging contrast media are not to be used as it passes the placenta. Ultrasound remains the primary screening modality for fetal pathology; fetal MRI can serve as an adjunct or second-line imaging modality.

  13. Positron emission tomographic studies using C-11-glucose in normal aging and cerebrovascular dementia

    International Nuclear Information System (INIS)

    Ujike, Takashi; Terashi, Akiro; Soeda, Toshiyuki; Kitamura, Shin; Kato, Toshiaki; Iio, Masaaki.

    1984-01-01

    Seven normal volunteers and 11 patients with cerebrovascular dementia were studied about the relations between effect of aging, severity of dementia, cerebral glucose metabolism and metabolic response to verbal stimuli by positron emission tomography (PET) using C-11-glucose. Regional distribution of glycogenic metabolites (RDGM: mg/100 g brain), which was a semi-quantitation of the pool of glycogenic metabolites mainly amino acids, were calculated. The RDGM values in elder normal subjects were significantly low compared with young normal subjects in frontal cortex (p < 0.05). The decline in frontal cortex metabolism could have been caused by the morphological changes in the course of aging. In temporal cortex, there was no significance between two groups. RDGM increased significantly respond to the verbal stimuli in frontal and temporal cortex both young and elder normal subjects. The RDGM values in vascular dementias were significantly low (p < 0.001) compared with elder normal subjects' in frontal and temporal cortex. Significant difference existed between mild and severe dementia in frontal cortex (p < 0.05). However, there was no significance between mild and severe dementias in temporal cortex. In mild dementias, RDGM increased significantly respond to the verbal stimuli in frontal and temporal cortex. In severe dementias, metabolic response to the verbal stimuli was less or lacking. Our results suggest that the cerebral metabolic functional reserve and the ability of the cerebral cortex to function respond to psychophysiologic stimulation are preserved in young and elder normal subjects and mild cerebrovascular dementias. (J.P.N.)

  14. Normal aging selectively diminishes alpha lateralization in visual spatial attention.

    Science.gov (United States)

    Hong, Xiangfei; Sun, Junfeng; Bengson, Jesse J; Mangun, George R; Tong, Shanbao

    2015-02-01

    EEG studies of cue-induced visual alpha power (8-13 Hz) lateralization have been conducted on young adults without examining differences that may develop as a consequence of normal aging. Here, we examined age-related differences in spatial attention by comparing healthy older and younger adults. Our key finding is that cue-induced alpha power lateralization was observed in younger, but not older adults, even though both groups exhibited classic event-related potential signatures of spatial orienting. Specifically, both younger and older adults showed significant early directing-attention negativity (EDAN), anterior directing-attention negativity (ADAN), late directing-attention positivity (LDAP) and contingent negative variation (CNV). Furthermore, target-evoked sensory components were enhanced for attended relative to unattended targets in both younger and older groups. This pattern of results suggests that although older adults can successfully allocate spatial attention, they do so without the lateralization of alpha power that is commonly observed in younger adults. Taken together, our findings demonstrate that younger and older adults might engage different neural mechanisms for attentional orienting, and that alpha power lateralization during visual spatial attention is a phenomenon that diminishes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2014-05-01

    Full Text Available Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD. This study uses a novel magnetic resonance imaging (MRI-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males completed an MRI at 1.5T, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001 and 32% in females (p < 0.01. Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05. In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05. In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

  16. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Diaz, Ricardo Gredilla; Weissman, Lior; Yang, JL

    2012-01-01

    Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging...... process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed...... suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms...

  17. Normal function of immunologic stem cells from aged mice

    International Nuclear Information System (INIS)

    Harrison, D.E.; Doubleday, J.W.

    1975-01-01

    Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

  18. Purposeful Engagement, Healthy Aging, and the Brain

    Science.gov (United States)

    Ryff, Carol D.; Heller, Aaron S.; Schaefer, Stacey M.; van Reekum, Carien; Davidson, Richard J.

    2016-01-01

    Purpose of review Research on psychological well-being in later life has identified strengths and vulnerabilities that occur with aging. We review the conceptual and philosophical foundations of a eudaimonic model of well-being and its empirical translation into six key dimensions of positive functioning. We also consider its implications for health, broadly defined. Recent findings Numerous findings from national longitudinal samples of U.S. adults are described. They show declining scores on purpose in life and personal growth with aging, but also underscore the notable variability among older persons in these patterns. Recently, health benefits have been identified among older adults who maintain high levels of a particular aspect of well-being, namely, purposeful life engagement. These benefits include extended longevity, reduced risk for various disease outcomes, reduced physiological dysregulation, and gene expression linked to better inflammatory profiles. The brain mechanisms that underlie such outcomes are also examined via a focus on affective style. Adults with higher levels of purpose in life show more rapid recovery from negative stimulus provocation, whereas those with higher well-being overall show sustained activation of reward circuitry in response to positive stimuli, and this pattern is associated with lower diurnal cortisol output. Volumetric findings (right insular gray matter volume) have also been linked with eudaimonic well-being. Summary Eudaimonic well-being predicts better health and longer lives, and thus constitutes an important direction for future research and practice. Intervention studies designed to promote well-being, including among those suffering from psychological disorders, are briefly described. PMID:28534002

  19. Age-Related Deviation of Gait from Normality in Alkaptonuria.

    Science.gov (United States)

    Barton, Gabor J; King, Stephanie L; Robinson, Mark A; Hawken, Malcolm B; Ranganath, Lakshminarayan R

    2015-01-01

    Alkaptonuria is a rare metabolic disease leading to systemic changes including early and severe arthropathy which affects mobility. For unknown reasons, the onset of degenerative changes is delayed to around 30 years of age when both objective and subjective symptoms develop. In order to complement description of the structural changes in alkaptonuria with measures of movement function, clinical gait analysis was added to the list of assessments in 2013. The aim of this study was to describe the deviation of gait from normality as a function of age in patients with alkaptonuria. Three-dimensional movement of reflective markers attached to joints were captured during walking in 39 patients and 10 controls. Subsequent to processing the data to emphasise the shape of marker trajectories, the mean Movement Deviation Profile was generated for all participants. This single number measure gives the deviation of a patient's gait from a distributed definition of gait normality. Results showed that gait deviation roughly follows a sigmoid profile with minimal increase of gait deviations in a younger patient group and an abrupt large increase around the second half of the 4th decade of life. Larger variations of gait deviations were found in the older group than in the younger group suggesting a complex interaction of multiple factors which determine gait function after symptoms manifest. Continued gait analysis of adults with AKU, extended to younger adults and children with AKU, is expected to complete understanding of both the natural history of alkaptonuria and how interventions can affect movement function.

  20. Age-and Brain Region-Specific Differences in Mitochondrial ...

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  1. Effects of normal aging on visuo-motor plasticity

    Science.gov (United States)

    Roller, Carrie A.; Cohen, Helen S.; Kimball, Kay T.; Bloomberg, Jacob J.

    2002-01-01

    Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuo-motor plasticity is a form of behavioral neural plasticity, which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into microgravity or an underwater environment. To determine the effects of aging on visuo-motor plasticity, we chose the simple and easily measured paradigm of visual-motor rearrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel modeling techniques for 73 subjects, aged 20 to 80 years. We found no statistically significant difference in measures of visuo-motor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

  2. Normal aging reduces motor synergies in manual pointing.

    Science.gov (United States)

    Verrel, Julius; Lövdén, Martin; Lindenberger, Ulman

    2012-01-01

    Depending upon its organization, movement variability may reflect poor or flexible control of a motor task. We studied adult age-related differences in the structure of postural variability in manual pointing using the uncontrolled manifold (UCM) method. Participants from 2 age groups (younger: 20-30 years; older: 70-80 years; 12 subjects per group) completed a total of 120 pointing trials to 2 different targets presented according to 3 schedules: blocked, alternating, and random. The age groups were similar with respect to basic kinematic variables, end point precision, as well as the accuracy of the biomechanical forward model of the arm. Following the uncontrolled manifold approach, goal-equivalent and nongoal-equivalent components of postural variability (goal-equivalent variability [GEV] and nongoal-equivalent variability [NGEV]) were determined for 5 time points of the movements (start, 10%, 50%, 90%, and end) and used to define a synergy index reflecting the flexibility/stability aspect of motor synergies. Toward the end of the movement, younger adults showed higher synergy indexes than older adults. Effects of target schedule were not reliable. We conclude that normal aging alters the organization of common multidegree-of-freedom movements, with older adults making less flexible use of motor abundance than younger adults. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

  4. Edited Magnetic Resonance Spectroscopy Detects an Age-related Decline in Brain GABA Levels

    OpenAIRE

    Gao, Fei; Edden, Richard A.E.; Li, Muwei; Puts, Nicolaas A.J.; Wang, Guangbin; Liu, Cheng; Zhao, Bin; Wang, Huiquan; Bai, Xue; Zhao, Chen; Wang, Xin; Barker, Peter B.

    2013-01-01

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy (1H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3 Tesl...

  5. A Network Flow-based Analysis of Cognitive Reserve in Normal Ageing and Alzheimer’s Disease

    Science.gov (United States)

    Wook Yoo, Sang; Han, Cheol E.; Shin, Joseph S.; Won Seo, Sang; Na, Duk L.; Kaiser, Marcus; Jeong, Yong; Seong, Joon-Kyung

    2015-01-01

    Cognitive reserve is the ability to sustain cognitive function even with a certain amount of brain damages. Here we investigate the neural compensation mechanism of cognitive reserve from the perspective of structural brain connectivity. Our goal was to show that normal people with high education levels (i.e., cognitive reserve) maintain abundant pathways connecting any two brain regions, providing better compensation or resilience after brain damage. Accordingly, patients with high education levels show more deterioration in structural brain connectivity than those with low education levels before symptoms of Alzheimer’s disease (AD) become apparent. To test this hypothesis, we use network flow measuring the number of alternative paths between two brain regions in the brain network. The experimental results show that for normal aging, education strengthens network reliability, as measured through flow values, in a subnetwork centered at the supramarginal gyrus. For AD, a subnetwork centered at the left middle frontal gyrus shows a negative correlation between flow and education, which implies more collapse in structural brain connectivity for highly educated patients. We conclude that cognitive reserve may come from the ability of network reorganization to secure the information flow within the brain network, therefore making it more resistant to disease progress. PMID:25992968

  6. Redox proteomics and the dynamic molecular landscape of the aging brain.

    Science.gov (United States)

    Perluigi, Marzia; Swomley, Aaron M; Butterfield, D Allan

    2014-01-01

    It is well established that the risk to develop neurodegenerative disorders increases with chronological aging. Accumulating studies contributed to characterize the age-dependent changes either at gene and protein expression level which, taken together, show that aging of the human brain results from the combination of the normal decline of multiple biological functions with environmental factors that contribute to defining disease risk of late-life brain disorders. Finding the "way out" of the labyrinth of such complex molecular interactions may help to fill the gap between "normal" brain aging and development of age-dependent diseases. To this purpose, proteomics studies are a powerful tool to better understand where to set the boundary line of healthy aging and age-related disease by analyzing the variation of protein expression levels and the major post translational modifications that determine "protein" physio/pathological fate. Increasing attention has been focused on oxidative modifications due to the crucial role of oxidative stress in aging, in addition to the fact that this type of modification is irreversible and may alter protein function. Redox proteomics studies contributed to decipher the complexity of brain aging by identifying the proteins that were increasingly oxidized and eventually dysfunctional as a function of age. The purpose of this review is to summarize the most important findings obtained by applying proteomics approaches to murine models of aging with also a brief overview of some human studies, in particular those related to dementia. Copyright © 2014. Published by Elsevier B.V.

  7. Destination memory and cognitive theory of mind in normal ageing.

    Science.gov (United States)

    El Haj, Mohamad; Raffard, Stéphane; Gély-Nargeot, Marie-Christine

    2016-01-01

    Destination memory is the ability to remember the destination to which a piece of information has been addressed (e.g., "Did I tell you about the promotion?"). This ability is found to be impaired in normal ageing. Our work aimed to link this deterioration to the decline in theory of mind. Forty younger adults (M age = 23.13 years, SD = 4.00) and 36 older adults (M age = 69.53 years, SD = 8.93) performed a destination memory task. They also performed the False-belief test addressing cognitive theory of mind and the Reading the mind in the eyes test addressing affective theory of mind. Results showed significant deterioration in destination memory, cognitive theory of mind and affective theory of mind in the older adults. The older adults' performance on destination memory was significantly correlated with and predicted by their performance on cognitive theory of mind. Difficulties in the ability to interpret and predict others' mental states are related to destination memory decline in older adults.

  8. Estimated maximal and current brain volume predict cognitive ability in old age.

    Science.gov (United States)

    Royle, Natalie A; Booth, Tom; Valdés Hernández, Maria C; Penke, Lars; Murray, Catherine; Gow, Alan J; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2013-12-01

    Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Estimated maximal and current brain volume predict cognitive ability in old age

    Science.gov (United States)

    Royle, Natalie A.; Booth, Tom; Valdés Hernández, Maria C.; Penke, Lars; Murray, Catherine; Gow, Alan J.; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

    2013-01-01

    Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. PMID:23850342

  10. Alteration of Venous Drainage Route in Idiopathic Normal Pressure Hydrocephalus and Normal Aging

    Science.gov (United States)

    Satow, Takeshi; Aso, Toshihiko; Nishida, Sei; Komuro, Taro; Ueno, Tsukasa; Oishi, Naoya; Nakagami, Yukako; Odagiri, Masashi; Kikuchi, Takayuki; Yoshida, Kazumichi; Ueda, Keita; Kunieda, Takeharu; Murai, Toshiya; Miyamoto, Susumu; Fukuyama, Hidenao

    2017-01-01

    Idiopathic normal pressure hydrocephalus (iNPH) is a highly prevalent condition in the elderly population; however, the underlying pathophysiology in relation to the aging process remains unclear. To investigate the effect of removal of cerebrospinal fluid by lumbar “tap test” on the cerebral circulation in patients with iNPH, 14 patients with “probable” iNPH were studied using a novel blood tracking technique based on blood oxygenation level-dependent (BOLD) magnetic resonance signal intensity. By tracking the propagation of the low-frequency component of the BOLD signal, extended venous drainage times were observed in the periventricular region of the patients, which was reversed by tap test. Interestingly, the venous drainage time in the periventricular region exhibited an age-related prolongation in the healthy control group. Additional regression analyses involving 81 control subjects revealed a dissociation of deep and superficial venous systems with increasing age, presumably reflecting focal inefficiency in the deep system. Our results not only provide insights into the etiology of iNPH, but also point to a potential non-invasive biomarker for screening iNPH. PMID:29218007

  11. Detecting brain growth patterns in normal children using tensor-based morphometry.

    Science.gov (United States)

    Hua, Xue; Leow, Alex D; Levitt, Jennifer G; Caplan, Rochelle; Thompson, Paul M; Toga, Arthur W

    2009-01-01

    Previous magnetic resonance imaging (MRI)-based volumetric studies have shown age-related increases in the volume of total white matter and decreases in the volume of total gray matter of normal children. Recent adaptations of image analysis strategies enable the detection of human brain growth with improved spatial resolution. In this article, we further explore the spatio-temporal complexity of adolescent brain maturation with tensor-based morphometry. By utilizing a novel non-linear elastic intensity-based registration algorithm on the serial structural MRI scans of 13 healthy children, individual Jacobian growth maps are generated and then registered to a common anatomical space. Statistical analyses reveal significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. In addition, a linear regression with age and gender suggests a slowing down of the growth rate in regions with the greatest white matter growth. We demonstrate that a tensor-based Jacobian map is a sensitive and reliable method to detect regional tissue changes during development. (c) 2007 Wiley-Liss, Inc.

  12. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....

  13. Functional brain imaging with SPECT in normal again and dementia. Methodological, pathophysiological, and diagnostic aspects

    International Nuclear Information System (INIS)

    Waldemar, G.

    1996-03-01

    New developments in instrumentation, radiochemistry, and data analysis, particularly the introduction of 99m Tc-labeled brain-retained tracers for perfusion studies, have opened up a new era of single photon emission computed tomography (SPECT). In this review critical methodological issues relating to the SPECT instrument, the radioactive tracers, the scanning procedure, the data analysis and interpretation of data, and subject selection are discussed together with the changes in regional cerebral blood flow (rCBF) observed in normal aging. An overview is given of the topography and the pathophysiological and diagnostic significance of focal rCBF deficits in Alzheimer's disease and in other dementia disorders, in which SPECT is capable of early or preclinical disease detection. In Alzheimer's disease, the diagnostic sensitivity and specificity of focal rCBF deficits measured with SPECT and brain-retained tracers are very high, in particular when combined with medial temporal lob atrophy on CT. Together with neuropsychological testing, SPECT serves to map the topography of brain dysfunction. Thus, in the clinical setting, SPECT provides information that is supplemental to that obtained in other studies. Future applications include neuroreceptor studies and treatment studies, in which SPECT may serve as a diagnostic aid in the selection of patients and as a potential mean for monitoring treatment effects. Although positron emission tomography is the best characterized tool for addressing some of these clinical and research issues in dementia, only the less expensive and technically simpler SPECT technique will have the potential of being available as a screening diagnostic instrument in the clinical setting. It is concluded that, properly approached, functional brain imaging with SPECT represents an important tool in the diagnosis, management, and research of dementia disorders. (au) 251 refs

  14. Atrophy of gray and white matters in the brain during aging

    International Nuclear Information System (INIS)

    Takeda, Shumpei; Matsuzawa, Taiju; Ito, Hisao.

    1984-01-01

    We studied atrophy of gray and white matter during aging in 57 males and 44 females with no neurological disturbances using x-ray computed tomography. The ages ranged from 12 to 80 years. Brain atrophy was expressed as brain volume index: 100% x [(brain volume/cranial cavity volume) in individual subjects]/[(brain volume/cranial cavity volume) in normal subjects of 20-39 years]. Atrophy of gray and white matter volume was expressed as gray and white matter volume indices: 100% x (apparent gray or white matter volume index in individual subjects)/(apparent gray or white matter volume index in normal subjects whose brain volume index was greater than 98%), where apparent gray and white matter volume indices were expressed as 100% x [(gray or white matter volume/cranial cavity volume) in individual subjects]/[(gray or white matter volume/cranial cavity volume) in normal subjects of 20-39 years]. Both the gray and white matter volume indices changed proportionally to the brain volume index (p<0.001). As the brain atrophy advanced, the gray matter volume index decreased more than the white matter volume index (P<0.001). Decrease in the gray and white matter volume indices was statistically significant only in seventies (P<0.002 for gray matter, P<0.05 for white matter). (author)

  15. Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

    Directory of Open Access Journals (Sweden)

    Sandra Zárate

    2017-12-01

    Full Text Available Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD. Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain.

  16. Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

    Science.gov (United States)

    Zárate, Sandra; Stevnsner, Tinna; Gredilla, Ricardo

    2017-01-01

    Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD). Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain. PMID:29311911

  17. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Norm software applets. Additionally, we have applied four different normalization approaches for normalization of the three target genes. We found using the NormFinder software that Ywhaz is the most stably expressed gene among the eight tested HKGs. However, the results of the analysis of the target genes...... are warranted. With the overall aim to inspect the gene expression of three target genes, NMDAR1, SORT, and CREB, in rat hippocampus, we tested a panel of eight HKGs, 18s rRNA, ActB, CycA, Gapd, Hmbs, Hprt1, Rpl13A, and Ywhaz in order to select the most stably expressed gene, using the NormFinder and ge...

  18. Plasticity of the aging brain: new directions in cognitive neuroscience.

    Science.gov (United States)

    Gutchess, Angela

    2014-10-31

    Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span. Copyright © 2014, American Association for the Advancement of Science.

  19. Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus.

    Science.gov (United States)

    Herukka, Sanna-Kaisa; Rummukainen, Jaana; Ihalainen, Jouni; von Und Zu Fraunberg, Mikael; Koivisto, Anne M; Nerg, Ossi; Puli, Lakshman K; Seppälä, Toni T; Zetterberg, Henrik; Pyykkö, Okko T; Helisalmi, Seppo; Tanila, Heikki; Alafuzoff, Irina; Hiltunen, Mikko; Rinne, Jaakko; Soininen, Hilkka; Jääskeläinen, Juha E; Leinonen, Ville

    2015-01-01

    Amyloid-β (Aβ1 - 42), total tau (T-tau), and phosphorylated tau (P-tau181) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble Aβ decreases with increasing age and advanced Aβ pathology as seen similarly in CSF. To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. Aβ1 - 42 and P-tau181 remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while Aβ1 - 42 levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF Aβ1 - 42 levels than those six without amyloid pathology. This is the first study to report ISF Aβ and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.

  20. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    Science.gov (United States)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  1. Stochastic simulations of normal aging and Werner's syndrome.

    KAUST Repository

    Qi, Qi

    2014-04-26

    Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner\\'s syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.

  2. Age-related changes of diffusional anisotropy in the cerebral white matter in normal subjects

    International Nuclear Information System (INIS)

    Hanyu, Haruo; Asano, Tetsuichi; Ogawa, Kimikazu; Takasaki, Masaru; Shindo, Hiroaki; Kakizaki, Dai; Abe, Kimihiko

    1997-01-01

    To investigate age-related changes of diffusional anisotropy in the cerebral white matter, we performed diffusion-weighted MRI studies in 21 normal subjects aged 25 to 96 years. The anisotropic rations (ARs), defined as the apparent diffusion coefficients perpendicular to the nerve fibers to those parallel to the nerve fibers, were significantly higher in elderly than in young subjects in the anterior and posterior white matter surrounding the lateral ventricle. Moreover, significant correlation between age and AR was found in the anterior white matter. The ventricular index (VI) measured on MRI, as a quantitative indicator of brain atrophy, was significantly higher in elderly than younger subjects, and significantly correlated with AR in the anterior white matter. Multiple regression analysis demonstrated that the VI showed the highest correlation for AR. On the other hand, there was no significant correlations between ARs in the corpus callosum and age. These results suggest that morphological changes in the myelin and axon in the white matter occur in elderly normal subjects, probably due to neuronal loss with aging. (author)

  3. Language in the aging brain: the network dynamics of cognitive decline and preservation.

    Science.gov (United States)

    Shafto, Meredith A; Tyler, Lorraine K

    2014-10-31

    Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults. Copyright © 2014, American Association for the Advancement of Science.

  4. Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits'

    Directory of Open Access Journals (Sweden)

    Marlijn H. de Beer

    2016-10-01

    Full Text Available Background/Aim: To explore the theory of ‘growing into deficits', a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH. Methods: Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results: Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30. Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7% patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion: In our opinion, the theory of ‘growing into deficits' shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis.

  5. Adaptation of brain functional and structural networks in aging.

    Directory of Open Access Journals (Sweden)

    Annie Lee

    Full Text Available The human brain, especially the prefrontal cortex (PFC, is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI, and high angular resolution diffusion imaging (HARDI, and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  6. Adaptation of brain functional and structural networks in aging.

    Science.gov (United States)

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  7. Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-01-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

  8. The effect of radioactive iodine on brain acetylcholine and serotonin in normal and stress subjected rats

    International Nuclear Information System (INIS)

    Hassan, S.S.; Mazumdar, S.; Prasad, G.C.; Udupa, K.N.

    1984-01-01

    The study was designed to throw light on the responses of brain acetylcholine and serotonin in the presence of 131 I in the brain in normal and stress subjected rats. 131 I irradiation in a mild dose increases the 5-hydroxytryptamine and acetylcholine content while shock stress reduces the acetylcholine content but increases the 5-hydroxytryptamine concentration in the brain. The 131 I treatment of shocked rats causes a decrease in 5-hydroxytryptamine and an increase in the acetylcholine content in the brain and it proves to be more effective when radioactive iodine is administered after inhibition of the thyroid activity by Lugol's iodine. (author)

  9. The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

    Science.gov (United States)

    Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M Okan; Botteron, Kelly N; McCracken, James; McKinstry, Robert C; Rivkin, Michael J; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo

    2016-01-01

    The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data. Published by Elsevier Inc.

  10. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    Science.gov (United States)

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  11. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Directory of Open Access Journals (Sweden)

    Sheng Xie

    Full Text Available Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  12. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Science.gov (United States)

    Xie, Sheng; Zhang, Zhe; Chang, Feiyan; Wang, Yishi; Zhang, Zhenxia; Zhou, Zhenyu; Guo, Hua

    2016-01-01

    Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  13. Divided attention and driving. The effects of aging and brain injury

    NARCIS (Netherlands)

    Withaar, Frederiec Kunna

    2000-01-01

    In this thesis, divided attention was investigated in four groups of subjects: closed head injury (CHI) patients, young control and healthy older subjects, and older subjects with cognitive impairments. It was studied how diffuse brain injury and normal and abnormal aging affect cognitive processes

  14. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    OpenAIRE

    Zamroziewicz, Marta K.; Barbey, Aron K.

    2016-01-01

    Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition?from entire diets to specific nutrients?affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nu...

  15. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84{+-}17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78{+-}10.36), mild defect (<50MQ : n=9, MQ=66.11{+-}13.87). The degree of rCBF decrease between the two groups was evaluated by {chi}{sup 2} test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients.

  16. Impaired Cardiac Function and Cognitive Brain Aging.

    Science.gov (United States)

    van der Velpen, Isabelle F; Yancy, Clyde W; Sorond, Farzaneh A; Sabayan, Behnam

    2017-12-01

    It is well established that patients with heart failure are at a greater risk for dementia. Recent evidence suggests that the heart-brain link goes beyond advanced heart failure, and even suboptimal cardiac function is associated with brain structural and functional changes leading to cognitive impairment. In this review, we address several pathophysiological mechanisms underlying this association, including hemodynamic stress and cerebral hypoperfusion, neuroinflammation, cardiac arrhythmias, and hypercoagulation. The close link between cardiac function and brain health has numerous clinical and public health implications. Cardiac dysfunction and cognitive impairment are both common in older adults. However, in our current clinical practice, these medical conditions are generally evaluated and treated in isolation. Emerging evidence on the significance of the heart-brain link calls for comprehensive cardiovascular risk assessment in patients with cognitive impairment and a neurocognitive workup in patients with impaired cardiac function. A multidisciplinary approach by cardiologists, neurologists, and geriatricians would benefit the diagnostic process and disease management and ultimately improve the quality of life for patients with cardiac and cognitive dysfunction. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  17. Soybean and tempeh total isoflvones improved antioxidant activities in normal and scopolamine-induced rat brain

    Directory of Open Access Journals (Sweden)

    Aliya Ahmad

    2015-11-01

    Full Text Available Objective: To highlight the comparative studies between total isoflavone extracts from soybean and tempeh on the neuronal oxidative stress and antioxidant activities. Methods: The total isoflavones were administered orally for 15 days with 3 selected doses (10, 20 and 40 mg/kg. Piracetam (400 mg/kg, p.o. was used as a standard drug while scopolamine (1 mg/kg, i.p. was used as a drug that promoted amnesia in selected groups. The oxidative markers (thiobarbituric acid reactive substances and nitric oxide were measured in brain homogenate. The antioxidant activities evaluated were catalase, superoxide dismutase, glutathione reductase and glutathione. Results: Our results showed that soybean and tempeh isoflavones significantly improved the levels of catalase, superoxide dismutase, glutathione reductase and glutathione while decreased levels of thiobarbituric acid reactive substances and nitric oxide in both the brain of normal as well as scopolamine-induced animals. Conclusions: Our findings suggested that soybean and tempeh isoflavones could be useful in the management and prevention of age-related neurodegenerative changes including Alzheimer’s disease through its antioxidant activities.

  18. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  19. Markers of Alzheimer’s Disease in Primary Visual Cortex in Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernández-Zimbrón

    2017-01-01

    Full Text Available Aging is the principal risk factor for the development of Alzheimer’s disease (AD. The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42 and abnormal hyperphosphorylation of Tau (p-Tau protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP, and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aβ42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging.

  20. Markers of Alzheimer's Disease in Primary Visual Cortex in Normal Aging in Mice

    Science.gov (United States)

    Perez-Hernández, Montserrat; Torres-Romero, Abigail; Gorostieta-Salas, Elisa; Gulias-Cañizo, Rosario; Quiroz-Mercado, Hugo

    2017-01-01

    Aging is the principal risk factor for the development of Alzheimer's disease (AD). The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42) and abnormal hyperphosphorylation of Tau (p-Tau) protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP), and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aβ42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging. PMID:29138750

  1. Accelerated Brain Aging in Schizophrenia : A Longitudinal Pattern Recognition Study

    NARCIS (Netherlands)

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  2. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

    Schnack, Hugo G.; Van Haren, Neeltje E M; Nieuwenhuis, Mireille; Pol, Hilleke E Hulshoff; Cahn, Wiepke; Kahn, René S.

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  3. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  4. Spectral Variability in the Aged Brain during Fine Motor Control

    Science.gov (United States)

    Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.

    2016-01-01

    Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231

  5. Quantifiable biomarkers of normal aging in the Japanese medaka fish (Oryzias latipes.

    Directory of Open Access Journals (Sweden)

    Lingling Ding

    2010-10-01

    Full Text Available Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes, a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research.The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old, mature adults (16 months old, and adults that had survived beyond the median lifespan (24 months. Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain.The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors.

  6. Imaging diagnosis in the elderly. Physiological and pathological changes in the aging brain

    International Nuclear Information System (INIS)

    Tokumaru, Aya M.; Saito, Yuko; Murayama, Shigeo

    2007-01-01

    The unprecedented aging of society is occurring rapidly Rather than a problem facing the future, this trend is already a reality in Japan. The discussion regarding the maintenance of the social environment surrounding medical care is important. Also important are the appropriate medical interventions for the diagnosis of various changes and conditions that are characteristic of the aging patient. However, it is extremely difficult to establish the border of morbid change if the brain-related change is normal. The main risk factor for the patient with dementia is aging itself. The neuroradiologist is an important source of precise imaging information as to what is normal and what is abnormal. (author)

  7. Selective vulnerability related to aging in large-scale resting brain networks.

    Science.gov (United States)

    Zhang, Hong-Ying; Chen, Wen-Xin; Jiao, Yun; Xu, Yao; Zhang, Xiang-Rong; Wu, Jing-Tao

    2014-01-01

    Normal aging is associated with cognitive decline. Evidence indicates that large-scale brain networks are affected by aging; however, it has not been established whether aging has equivalent effects on specific large-scale networks. In the present study, 40 healthy subjects including 22 older (aged 60-80 years) and 18 younger (aged 22-33 years) adults underwent resting-state functional MRI scanning. Four canonical resting-state networks, including the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN) and salience network, were extracted, and the functional connectivities in these canonical networks were compared between the younger and older groups. We found distinct, disruptive alterations present in the large-scale aging-related resting brain networks: the ECN was affected the most, followed by the DAN. However, the DMN and salience networks showed limited functional connectivity disruption. The visual network served as a control and was similarly preserved in both groups. Our findings suggest that the aged brain is characterized by selective vulnerability in large-scale brain networks. These results could help improve our understanding of the mechanism of degeneration in the aging brain. Additional work is warranted to determine whether selective alterations in the intrinsic networks are related to impairments in behavioral performance.

  8. Investigation of olfactory function in normal volunteers by Tc-99m ECD Brain SPECT: Analysis using statistical parametric mapping

    International Nuclear Information System (INIS)

    Chung, Y.A.; Kim, S.H.; Park, Y.H.; Lee, S.Y.; Sohn, H.S.; Chung, S.K.

    2002-01-01

    The purpose of this study was to investigate olfactory function according to Tc-99m ECD uptake pattern in brain perfusion SPET of normal volunteer by means of statistical parametric mapping (SPM) analysis. The study population was 8 healthy volunteer subjects (M:F = 6:2, age range: 22-54 years, mean 34 years). We performed baseline brain perfusion SPET using 555 MBq of Tc-99m ECD in a silent dark room. Two hours later, we obtained brain perfusion SPET using 1110 MBq of Tc-99m ECD after 3% butanol solution under the same condition. All SPET images were spatially transformed to standard space smoothed and globally normalized. The differences between the baseline and odor-identification SPET images were statistically analyzed using SPM-99 software. The difference between two sets of brain perfusion SPET was considered significant at a threshold of uncorrected p values less than 0.01. SPM analysis revealed significant hyper-perfusion in both cingulated gyri, right middle temporal gyrus, right superior and inferior frontal gyri, right lingual gyrus and right fusiform gyrus on odor-identification SPET. This study shows that brain perfusion SPET can securely support other diagnostic techniques in the evaluation of olfactory function

  9. Nutritional strategies to optimise cognitive function in the aging brain.

    Science.gov (United States)

    Wahl, Devin; Cogger, Victoria C; Solon-Biet, Samantha M; Waern, Rosilene V R; Gokarn, Rahul; Pulpitel, Tamara; Cabo, Rafael de; Mattson, Mark P; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

    2016-11-01

    Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Brain aging and neurodegeneration: from a mitochondrial point of view.

    Science.gov (United States)

    Grimm, Amandine; Eckert, Anne

    2017-11-01

    Aging is defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the 'free-radical theory of aging', because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species. Thus, in this review, we aim to look at brain aging processes from a mitochondrial point of view by asking: (i) What happens to brain mitochondrial bioenergetics and dynamics during aging? (ii) Why is the brain so sensitive to the age-related mitochondrial impairments? (iii) Is there a sex difference in the age-induced mitochondrial dysfunction? Understanding mitochondrial physiology in the context of brain aging may help identify therapeutic targets against neurodegeneration. This article is part of a series "Beyond Amyloid". © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  11. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Young, E-mail: eyhan@uams.edu [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Moros, Eduardo [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL (United States); Corry, Peter [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  12. Insulin, Aging, and the Brain: Mechanisms and Implications

    OpenAIRE

    Akintola, Abimbola A.; van Heemst, Diana

    2015-01-01

    There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into t...

  13. Roles and regulation of brain glutamate transporters in normal and pathological brain function

    International Nuclear Information System (INIS)

    O'Shea, R.D.

    2001-01-01

    Full text: Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS. Synaptically released Glu acts on both ionotropic (iGluR) and metabotropic receptors, and excessive iGluR activation results in neuronal death (termed excitotoxicity). Removal of Glu from the synapse is thus critical for normal transmission and to prevent excitotoxicity, and is performed exclusively by a family of excitatory amino acid transporters (EAATs, also known as glutamate transporters). Disregulation of Glu transport may contribute to the pathogenesis of many neurodegenerative conditions, and altered expression or function of EAATs has been identified in a number of these pathologies. These studies investigated the functional and pathological effects of EAAT inhibitors in vitro, and developed a novel screening assay for compounds with activity at EAATs. Astrocytic EAATs are responsible for the majority of Glu uptake in brain, so preparations containing both astrocytes and neurones are required to analyse the contribution of EAATs to neuroprotection. Organotypic hippocampal cultures (OHCs), which exhibit many of the features of the intact CNS, were prepared from 11-14 day old Sprague Dawley rats (anaesthetised with halothane). Hippocampal slices (350 μm thick) were maintained on culture well inserts in chemically defined medium. After 2 weeks, cultures were treated with EAAT inhibitors for 3-7 days in the presence or absence of 300 μM Glu. Treatment with most EAAT inhibitors resulted in cell death that was proportional to the Glu concentration in the medium. In contrast, (2S,3S,4R)-2-(carboxycyclopropyl)glycine (L-CCG-III), a competitive substrate at EAATs (and possibly an antagonist at the kainate subtype of iGluR), appeared to be neuroprotective: increased Glu was not toxic in the presence of this drug. These results demonstrate the sensitivity of OHCs to inhibition of Glu uptake, highlighting the importance of EAATs in preventing excitotoxicity. Since modulation of

  14. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Science.gov (United States)

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K; Engelhard, Kristin; Thal, Serge C

    2012-01-01

    After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation

  15. Omega-3 polyunsaturated fatty acids and brain aging.

    Science.gov (United States)

    Denis, Isabelle; Potier, Brigitte; Heberden, Christine; Vancassel, Sylvie

    2015-03-01

    The literature on the influence of dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) on brain aging has grown exponentially during the last decade. Many avenues have been explored but no global picture or clear evidence has emerged. Experimental studies have shown that ω-3 PUFA is involved in many neurobiological processes that are involved in neurotransmission and neuroprotection, indicating that these PUFAs may prevent age-related brain damage. Human studies have revealed only a weak link between ω-3 PUFA status and cognitive aging, whereas interventional studies have yet to confirm it. The purpose of this review is to analyze the developments in the area during the last 2 years. Human brain MRI studies have confirmed previous findings that ω-3 PUFA can protect the brain during aging; two intervention studies obtained clear evidence. We also analyzed the experimental data clarifying the involvement of ω-3 PUFA in neurotransmission, neuroprotection (including prevention of peroxidation, inflammation, and excitotoxicity), and neurogenesis, thereby helping the brain cope with aging. These recent human and experimental studies provide support for and clarification of how ω-3 PUFA protect against brain aging and highlight the main lines for future research.

  16. The effects of physical activity, education, and body mass index on the aging brain.

    Science.gov (United States)

    Ho, April J; Raji, Cyrus A; Becker, James T; Lopez, Oscar L; Kuller, Lewis H; Hua, Xue; Dinov, Ivo D; Stein, Jason L; Rosano, Caterina; Toga, Arthur W; Thompson, Paul M

    2011-09-01

    Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 ± 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with ~2-3% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with ~2-2.5% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another. Copyright © 2010 Wiley-Liss, Inc.

  17. Brain Aging and Late-Onset Alzheimer's Disease: A Matter of Increased Amyloid or Reduced Energy?

    Science.gov (United States)

    Mecocci, Patrizia; Baroni, Marta; Senin, Umberto; Boccardi, Virginia

    2018-03-16

    Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages. The pathogenetic amyloid cascade hypothesis has been recently questioned due to multiple clinical failures. Furthermore, several studies reported that cognitively normal elderly have a high amyloid deposition in the brain comparable to the levels observed in old age subjects with AD. This suggests that amyloid accumulation enters into the normal process of aging and what really triggers neuronal death and clinical manifestation in late-onset AD still needs further explanation. In this context, 'normal brain aging' and AD might represent a different pathway of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes affecting the brain may be considered as biologic manifestations of increasing entropy. Bioenergetic deficits due to mitochondrial dysfunction may lead to progressive neuronal death and clinical expression of dementia. So, increased amyloid in the brain of old age subjects may represent the downstream event expression of a biological system that is cooling down because of its exhaustion and not the core causative factor of late-onset dementia.

  18. Chronic microelectrode investigations of normal human brain physiology using a hybrid depth electrode.

    Science.gov (United States)

    Howard, M A; Volkov, I O; Noh, M D; Granner, M A; Mirsky, R; Garell, P C

    1997-01-01

    Neurosurgeons have unique access to in vivo human brain tissue, and in the course of clinical treatment important scientific advances have been made that further our understanding of normal brain physiology. In the modern era, microelectrode recordings have been used to systematically investigate the cellular properties of lateral temporal cerebral cortex. The current report describes a hybrid depth electrode (HDE) recording technique that was developed to enable neurosurgeons to simultaneously investigate normal cellular physiology during chronic intracranial EEG recordings. The HDE combines microelectrode and EEG recordings sites on a single shaft. Multiple microelectrode recordings are obtained from MRI defined brain sites and single-unit activity is discriminated from these data. To date, over 60 HDEs have been placed in 20 epilepsy surgery patients. Unique physiologic data have been gathered from neurons in numerous brain regions, including amygdala, hippocampus, frontal lobe, insula and Heschl's gyrus. Functional activation studies were carried out without risking patient safety or comfort.

  19. Different strategies for auditory word recognition in healthy versus normal aging.

    Science.gov (United States)

    Aine, C J; Bryant, J E; Knoefel, J E; Adair, J C; Hart, B; Donahue, C H; Montaño, R; Hayek, R; Qualls, C; Ranken, D; Stephen, J M

    2010-02-15

    To explore the effects of commonly encountered pathology on auditory recognition strategies in elderly participants, magnetoencephalographic (MEG) brain activation patterns and performance were examined in 30 elderly [18 controls and 12 elderly with mild cognitive impairment (MCI) or probable Alzheimer's disease (AD)]. It was predicted that participants with known pathology would reveal different networks of brain activation, compared to healthy elderly, which should correlate with poorer performance. Participants heard a list of words representing common objects, twice. After 20 minutes a list of new and old words was presented and participants judged whether each word was heard earlier. MEG responses were analyzed using a semiautomated source modeling procedure. A cluster analysis using all subjects' MEG sources revealed three dominant patterns of activity which correlated with IQ and task performance. The highest performing group revealed activity in premotor, anterior temporal, and superior parietal lobes with little contribution from prefrontal cortex. Performance and brain activation patterns were also compared for individuals with or without abnormalities such as white matter hyperintensities and/or volume reduction evidenced on their MRIs. Memory performance and activation patterns for individuals with white matter hyperintensities resembled the group of MCI/AD patients. These results emphasize the following: (1) general pathology correlates with cognitive decline and (2) full characterization of the health of elderly participants is important in studies of normal aging since random samples from the elderly population are apt to include individuals with subclinical pathology that can affect cognitive performance. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

    Science.gov (United States)

    Zamroziewicz, Marta K; Barbey, Aron K

    2016-01-01

    Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  1. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Directory of Open Access Journals (Sweden)

    Marta Karolina Zamroziewicz

    2016-06-01

    Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  2. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model.

    Directory of Open Access Journals (Sweden)

    Habib Baghirov

    Full Text Available The treatment of brain diseases is hindered by the blood-brain barrier (BBB preventing most drugs from entering the brain. Focused ultrasound (FUS with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.

  3. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

    Science.gov (United States)

    Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Åslund, Andreas K. O.

    2018-01-01

    The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma. PMID:29338016

  4. Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson's disease.

    Science.gov (United States)

    Rouillard, Maud; Audiffren, Michel; Albinet, Cédric; Ali Bahri, Mohamed; Garraux, Gaëtan; Collette, Fabienne

    2017-03-01

    Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and

  5. Neural underpinnings of background acoustic noise in normal aging and mild cognitive impairment.

    Science.gov (United States)

    Sinanaj, Indrit; Montandon, Marie-Louise; Rodriguez, Cristelle; Herrmann, François; Santini, Francesco; Haller, Sven; Giannakopoulos, Panteleimon

    2015-12-03

    Previous contributions in younger cohorts have revealed that reallocation of cerebral resources, a crucial mechanism for working memory (WM), may be disrupted by parallel demands of background acoustic noise suppression. To date, no study has explored the impact of such disruption on brain activation in elderly individuals with or without subtle cognitive deficits. We performed a functional Magnetic Resonance Imaging (fMRI) study in 23 cases (mean age=75.7 y.o., 16 men) with mild cognitive impairment (MCI) and 16 elderly healthy controls (HC, mean age=70.1 y.o., three men) using a 2-back WM task, under two distinct MRI background acoustic noise conditions (louder vs. lower noise echo-planar imaging). General linear models were used to assess brain activation as a function of group and noise. In both groups, lower background noise is associated with increased activation of the working memory network (WMN). A decrease of the normally observed deactivation of the default mode network (DMN) is found under louder noise in both groups. Unlike HC, MCI cases also show decreased deactivation of the DMN under both louder and lower background noise. Under louder noise, this decrease is observed in anterior parts of the DMN in HC, and in the posterior cingulate cortex in MCI cases. Our results suggest that background acoustic noise has a differential impact on WMN activation in normal aging as a function of the cognitive status. Only louder noise has a disruptive effect on the usually observed DMN deactivation during WM task performance in HC. In contrast, MCI cases show altered DMN reactivity even in the presence of lower noise. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Prostate stem cell antigen is expressed in normal and malignant human brain tissues.

    Science.gov (United States)

    Ono, Hiroe; Sakamoto, Hiromi; Yoshida, Teruhiko; Saeki, Norihisa

    2018-03-01

    Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and exhibits an organ-dependent expression pattern in cancer. PSCA is upregulated in prostate cancer and downregulated in gastric cancer. PSCA is expressed in a variety of human organs. Although certain studies previously demonstrated its expression in the mammalian and avian brain, its expression in the human brain has not been thoroughly elucidated. Additionally, it was previously reported that PSCA is weakly expressed in the astrocytes of the normal human brain but aberrantly expressed in glioma, suggesting that PSCA is a promising target of glioma therapy and prostate cancer therapy. The current study identified PSCA expression in the neural and choroid plexus cells of the normal human brain by immunohistochemistry. In brain tumors, PSCA was expressed in medulloblastoma and glioma, and its expression was also observed in papilloma and papillary carcinoma of the choroid plexus, ependymoma and meningioma. The results suggest that PSCA may have a tumor-promoting function in brain tumors and is a potential target for their therapy. However, its expression in normal neuronal and choroid plexus cells implies that a PSCA-targeted therapy may lead to certain adverse phenomena.

  7. Emotion and Aging: Evidence from Brain and Behavior

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2014-09-01

    Full Text Available Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the thirteen papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  8. Assessment the Plasticity of Cortical Brain Theory through Visual Memory in Deaf and Normal Students

    Directory of Open Access Journals (Sweden)

    Ali Ghanaee-Chamanabad

    2012-10-01

    Full Text Available Background: The main aim of this research was to assess the differences of visual memory in deaf and normal students according to plasticity of cortical brain.Materials and Methods: This is an ex-post factor research. Benton visual test was performed by two different ways on 46 students of primary school. (22 deaf and 24 normal students. The t-student was used to analysis the data. Results: The visual memory in deaf students was significantly higher than the similar normal students (not deaf.While the action of visual memory in deaf girls was risen in comparison to normal girls in both ways, the deaf boys presented the better action in just one way of the two performances of Benton visual memory test.Conclusion: The action of plasticity of brain shows that the brain of an adult is dynamic and there are some changes in it. This brain plasticity has not limited to sensory somatic systems. Therefore according to plasticity of cortical brain theory, the deaf students due to the defect of hearing have increased the visual the visual inputs which developed the procedural visual memory.

  9. MRI assessment of whole-brain structural changes in aging.

    Science.gov (United States)

    Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

    2017-01-01

    One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P age ( r 2 >0.29; P 26.48, P aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

  10. Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

    Science.gov (United States)

    Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

    2017-07-01

    Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

  11. Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy.

    Science.gov (United States)

    Ibáñez, Vicente; Pietrini, Pietro; Furey, Maura L; Alexander, Gene E; Millet, Philippe; Bokde, Arun L W; Teichberg, Diane; Schapiro, Mark B; Horwitz, Barry; Rapoport, Stanley I

    2004-03-15

    Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with 18F-fluoro-2-deoxy-d-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical, and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus, statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state.

  12. Central region morphometry in a child brain; Age and gender ...

    African Journals Online (AJOL)

    2013-10-10

    Oct 10, 2013 ... gender in three different age groups (aged 6‑9, 10‑13, and 14‑17). Results: Central region measures of the brains of boys aged 6‑17 are higher than girls except for MS‑PC distance. While. VCS‑PC, CS‑PC, and MS‑PC measures display a significant difference in the girls aged 14‑17 when compared to the.

  13. N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2015-09-01

    To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

  14. Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis

    OpenAIRE

    Prezado, Yolanda; Jouvion, Gregory; Hardy, David; Patriarca, Annalisa; Nauraye, Catherine; Bergs, Judith; González, Wilfredo; Guardiola, Consuelo; Juchaux, Marjorie; Labiod, Dalila; Dendale, Remi; Jourdain, Laurène; Sebrie, Catherine; Pouzoulet, Frederic

    2017-01-01

    Proton minibeam radiation therapy (pMBRT) is a novel strategy for minimizing normal tissue damage resulting from radiotherapy treatments. This strategy partners the inherent advantages of protons for radiotherapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated beams. In this study, whole brains (excluding the olfactory bulb) of Fischer 344 rats (n = 16) were irradiated at the Orsay Proton Therapy Center. Half of the animals received st...

  15. Brain changes in overweight/obese and normal-weight adults with type 2 diabetes mellitus.

    Science.gov (United States)

    Yoon, Sujung; Cho, Hanbyul; Kim, Jungyoon; Lee, Do-Wan; Kim, Geon Ha; Hong, Young Sun; Moon, Sohyeon; Park, Shinwon; Lee, Sunho; Lee, Suji; Bae, Sujin; Simonson, Donald C; Lyoo, In Kyoon

    2017-07-01

    Overweight and obesity may significantly worsen glycaemic and metabolic control in type 2 diabetes. However, little is known about the effects of overweight and obesity on the brains of people with type 2 diabetes. Here, we investigate whether the presence of overweight or obesity influences the brain and cognitive functions during early stage type 2 diabetes. This study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in their brain structures and cognition during early stage type 2 diabetes compared with participants with normal weight. Relationships between each of these measures and disease duration were also examined. Global mean cortical thickness was lower in the overweight/obese type 2 diabetes group than in the normal-weight type 2 diabetes group (z = -2.96, p for group effect = 0.003). A negative correlation was observed between disease duration and global mean white matter integrity (z = 2.42, p for interaction = 0.02) in the overweight/obese type 2 diabetes group, but not in the normal-weight type 2 diabetes group. Overweight/obese individuals with type 2 diabetes showed a decrease in psychomotor speed performance related to disease duration (z = -2.12, p for interaction = 0.03), while normal-weight participants did not. The current study attempted to uncouple the effects of overweight/obesity from those of type 2 diabetes on brain structures and cognition. Overweight/obese participants with type 2 diabetes had more severe and progressive abnormalities in brain structures and cognition during early stage type 2 diabetes compared with normal-weight participants.

  16. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

  17. Nutrition for the ageing brain: Towards evidence for an optimal diet.

    Science.gov (United States)

    Vauzour, David; Camprubi-Robles, Maria; Miquel-Kergoat, Sophie; Andres-Lacueva, Cristina; Bánáti, Diána; Barberger-Gateau, Pascale; Bowman, Gene L; Caberlotto, Laura; Clarke, Robert; Hogervorst, Eef; Kiliaan, Amanda J; Lucca, Ugo; Manach, Claudine; Minihane, Anne-Marie; Mitchell, Ellen Siobhan; Perneczky, Robert; Perry, Hugh; Roussel, Anne-Marie; Schuermans, Jeroen; Sijben, John; Spencer, Jeremy P E; Thuret, Sandrine; van de Rest, Ondine; Vandewoude, Maurits; Wesnes, Keith; Williams, Robert J; Williams, Robin S B; Ramirez, Maria

    2017-05-01

    As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Impact of apolipoprotein E ε4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging.

    Science.gov (United States)

    Chang, L; Andres, M; Sadino, J; Jiang, C S; Nakama, H; Miller, E; Ernst, T

    2011-10-15

    The apolipoprotein E (APOE) ε4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOEε4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated. Automated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects]. Compared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOEε4- subjects, SN controls with APOEε4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOEε4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (younger APOEε4+HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-status×APOEε4×Age) interaction-p-values=0.005 to 0.03]. These findings suggest that APOEε4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOEε4 allele(s). Early screening for the APOEε4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-06-01

    Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks' λ = 0.324, χ(2) (3) = 38.907, p tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

  20. High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation. Normal foetal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Scola, Elisa; Palumbo, Giovanni; Avignone, Sabrina; Cinnante, Claudia Maria [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Conte, Giorgio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Boito, Simona; Persico, Nicola [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Department of Obstetrics and Gynaecology ' L. Mangiagalli' , Milan (Italy); Rizzuti, Tommaso [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Pathology Unit, Milan (Italy); Triulzi, Fabio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan (Italy)

    2018-01-15

    To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. (orig.)

  1. Normalization.

    Science.gov (United States)

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  2. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy

    International Nuclear Information System (INIS)

    Esteve, Francois; Rubin, Christophe; Grand, Sylvie; Kolodie, Helene; Le Bas, Jean-Francois

    1998-01-01

    Purpose: To observe the time course of the proton magnetic resonance spectroscopy ( 1 H-MRS) variations due to radiation therapy on normal human brain. Methods and Materials: We followed 11 patients receiving an exclusive external radiation therapy for brain tumor for 8 months. They underwent proton MRS scans before any radiation exposure and 1, 4, and 8 months after they began the radiation therapy. The patients received 60 Gy in tumoral area fractionated over 6 weeks. The contralateral normal brain hemisphere received a radiation dose from 20 to 50 Gy. The main metabolite concentrations (N-acetylaspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate (Lac) were evaluated by the areas of the peaks after peak fitting. Normalized values (NV) were obtained by processing the ratio of the peak area of a given metabolite to the sum of all the spectrum peak areas; ratios (NAA/Cho, NAA/Cr, and Cho/Cr) were processed. One patient, who received panencephalic radiotherapy (30 Gy) after metastasectomy from a primary kidney adenocarcinoma, has been monitored with 1 H-MRS eight times for 6 months to observe the onset of the metabolic changes. Results: Changes were observed in irradiated normal brain tissue 4 months after radiation therapy began: the NAA/Cho and NAA/Cr ratios and the NAA (NV) decreased while the Choline (NV) increased. Four months later, normal values were recovered. Conclusion: 1 H-MRS has the potentiality to detect and to evaluate in vivo early adverse metabolic effects of radiation therapy in the normal human brain. These changes are significant 4 months after the radiation therapy began and appear to resolve over time

  3. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers.

    Science.gov (United States)

    Li, X; Andres, A; Shankar, K; Pivik, R T; Glasier, C M; Ramakrishnaiah, R H; Zhang, Y; Badger, T M; Ou, X

    2016-12-01

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal-weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (Pmaternal intelligence quotient, gestational weight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (Pmaternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain.

  4. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    OpenAIRE

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing...

  5. Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis.

    Science.gov (United States)

    Prezado, Yolanda; Jouvion, Gregory; Hardy, David; Patriarca, Annalisa; Nauraye, Catherine; Bergs, Judith; González, Wilfredo; Guardiola, Consuelo; Juchaux, Marjorie; Labiod, Dalila; Dendale, Remi; Jourdain, Laurène; Sebrie, Catherine; Pouzoulet, Frederic

    2017-10-31

    Proton minibeam radiation therapy (pMBRT) is a novel strategy for minimizing normal tissue damage resulting from radiotherapy treatments. This strategy partners the inherent advantages of protons for radiotherapy with the gain in normal tissue preservation observed upon irradiation with narrow, spatially fractionated beams. In this study, whole brains (excluding the olfactory bulb) of Fischer 344 rats (n = 16) were irradiated at the Orsay Proton Therapy Center. Half of the animals received standard proton irradiation, while the other half were irradiated with pMBRT at the same average dose (25 Gy in one fraction). The animals were followed-up for 6 months. A magnetic resonance imaging (MRI) study using a 7-T small-animal MRI scanner was performed along with a histological analysis. Rats treated with conventional proton irradiation exhibited severe moist desquamation, permanent epilation and substantial brain damage. In contrast, rats in the pMBRT group exhibited no skin damage, reversible epilation and significantly reduced brain damage; some brain damage was observed in only one out of the eight irradiated rats. These results demonstrate that pMBRT leads to an increase in normal tissue resistance. This net gain in normal tissue sparing can lead to the efficient treatment of very radio-resistant tumours, which are currently mostly treated palliatively.

  6. Morphometric connectivity analysis to distinguish normal, mild cognitive impaired, and Alzheimer subjects based on brain MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge; Mysling, Peter

    2013-01-01

    This work investigates a novel way of looking at the regions in the brain and their relationship as possible markers to classify normal control (NC), mild cognitive impaired (MCI), and Alzheimer Disease (AD) subjects. MRI scans from a subset of 101 subjects from the ADNI study at baseline was used...

  7. A voxel-based morphometric magnetic resonance imaging study of the brain detects age-related gray matter volume changes in healthy subjects of 21–45 years old

    OpenAIRE

    Bourisly, Ali K; El-Beltagi, Ahmed; Cherian, Jigi; Gejo, Grace; Al-Jazzaf, Abrar; Ismail, Mohammad

    2015-01-01

    Previous and more recent work of analyzing structural changes in the brain suggest that certain brain regions such as the frontal lobe are among the brain regions profoundly affected by the aging process across males and females. Also, a unified model of structural changes in a normally aging brain is still lacking. The present study investigated age-related structural brain changes in gray matter from young to early middle-age adulthood for males and females. Magnetic resonance images of 215...

  8. A Novel Brain Network Construction Method for Exploring Age-Related Functional Reorganization

    Directory of Open Access Journals (Sweden)

    Wei Li

    2016-01-01

    Full Text Available The human brain undergoes complex reorganization and changes during aging. Using graph theory, scientists can find differences in topological properties of functional brain networks between young and elderly adults. However, these differences are sometimes significant and sometimes not. Several studies have even identified disparate differences in topological properties during normal aging or in age-related diseases. One possible reason for this issue is that existing brain network construction methods cannot fully extract the “intrinsic edges” to prevent useful signals from being buried into noises. This paper proposes a new subnetwork voting (SNV method with sliding window to construct functional brain networks for young and elderly adults. Differences in the topological properties of brain networks constructed from the classic and SNV methods were consistent. Statistical analysis showed that the SNV method can identify much more statistically significant differences between groups than the classic method. Moreover, support vector machine was utilized to classify young and elderly adults; its accuracy, based on the SNV method, reached 89.3%, significantly higher than that with classic method. Therefore, the SNV method can improve consistency within a group and highlight differences between groups, which can be valuable for the exploration and auxiliary diagnosis of aging and age-related diseases.

  9. A Novel Brain Network Construction Method for Exploring Age-Related Functional Reorganization.

    Science.gov (United States)

    Li, Wei; Wang, Miao; Li, Yapeng; Huang, Yue; Chen, Xi

    2016-01-01

    The human brain undergoes complex reorganization and changes during aging. Using graph theory, scientists can find differences in topological properties of functional brain networks between young and elderly adults. However, these differences are sometimes significant and sometimes not. Several studies have even identified disparate differences in topological properties during normal aging or in age-related diseases. One possible reason for this issue is that existing brain network construction methods cannot fully extract the "intrinsic edges" to prevent useful signals from being buried into noises. This paper proposes a new subnetwork voting (SNV) method with sliding window to construct functional brain networks for young and elderly adults. Differences in the topological properties of brain networks constructed from the classic and SNV methods were consistent. Statistical analysis showed that the SNV method can identify much more statistically significant differences between groups than the classic method. Moreover, support vector machine was utilized to classify young and elderly adults; its accuracy, based on the SNV method, reached 89.3%, significantly higher than that with classic method. Therefore, the SNV method can improve consistency within a group and highlight differences between groups, which can be valuable for the exploration and auxiliary diagnosis of aging and age-related diseases.

  10. Relationship between age, radiographic normal heart size and ...

    African Journals Online (AJOL)

    Background: Cardio-vascular disease (CVD) is now on the increase. The precise diagnosis of CVD is of immense clinical importance to the cardiac surgeons, pathologist and also for cardiologists. However, information on normal values for various cardio-vascular structures in Nigeria, a country with the highest population ...

  11. Changes in intellectual functioning associated with normal aging.

    Science.gov (United States)

    Miller, Lori J; Myers, Allison; Prinzi, Lena; Mittenberg, Wiley

    2009-11-01

    Declines in IQ scores with advancing age have been observed in each successive revision of the Wechsler Intelligence Scales. This study examined age-related changes on the fourth edition of the Wechsler Adult Intelligence Scale and compared these to the effects seen on the 1955, 1981, and 1997 standardizations of the scales. The most pronounced declines were in measures of processing speed and nonverbal reasoning. Declines in nonverbal reasoning were similar on timed and un-timed measures. Verbal abilities remained relatively stable across the life span. General intelligence as assessed by the Full Scale IQ was reduced about 1 SD by age 75 when corrections for age were removed. Age-related declines have become less pronounced since 1955, particularly on measures of processing speed. This effect was essentially linear, unrelated to concurrent IQ increases in the general population, and paralleled a 9-year increase in life expectancy during this time period.

  12. In vivo calcium imaging of the aging and diseased brain

    International Nuclear Information System (INIS)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga

    2008-01-01

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  13. The role of mitochondrial ROS in the aging brain.

    Science.gov (United States)

    Stefanatos, Rhoda; Sanz, Alberto

    2018-03-01

    The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging. © 2017 Federation of European Biochemical Societies.

  14. Age-related brain atrophy and mental deterioration - a study with computed tomography

    International Nuclear Information System (INIS)

    Ito, M.; Hatazawa, J.; Yamaura, H.; Matsuzawa, T.

    1981-01-01

    The relation of brain atrophy measured with computed tomography (CT) to mental deterioration on living people was studied. A newly improved technique for quantitative measurement of brain atrophy was developed. The pixels inside the head slices were divided into three parts; brain skull, and cerebrospinal fluid according to their CT number. The volume of brain, CSF, and cranial cavity were calculated by counting the number of pixels of each tissue. Results from 130 normal brains showed that the CSF volume was constant at about 16 ml through 20-39 years old. After 40 years the mean CSF volume increased drastically and reached 71 ml in the seventies. The volume of the brain was standardized for comparison between different-sized heads (brain volume index: BVI). The mean BVI decreased with statistical significance after 40 years of age. Mental function of these persons were evaluated using Hasegawa's dementia rating scale for the elderly. Progression of brain atrophy accompanied loss of mental activities (p<0.01). (author)

  15. The dopaminergic system in the aging brain of Drosophila

    Directory of Open Access Journals (Sweden)

    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

  16. The dopaminergic system in the aging brain of Drosophila.

    Science.gov (United States)

    White, Katherine E; Humphrey, Dickon M; Hirth, Frank

    2010-01-01

    Drosophila models of Parkinson's disease are characterized by two principal phenotypes: the specific loss of dopaminergic (DA) neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analyzed the DA system and motor behavior in aging Drosophila. DA neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH > mCD8::GFP and cell type-specific MARCM clones revealed that DA neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, DA neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity, and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH > Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct DA behaviors in Drosophila. Moreover, DA neurons were maintained between early- and late life, as quantified by TH > mCD8::GFP and anti-TH labeling, indicating that adult onset, age-related degeneration of DA neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson's disease as well as other disorders affecting DA neurons and movement control.

  17. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    Science.gov (United States)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  18. Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

    Energy Technology Data Exchange (ETDEWEB)

    Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail: sorl@rn.dk; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)

    2013-10-15

    Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

  19. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Science.gov (United States)

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice.

    Science.gov (United States)

    Guo, Janet; Bakshi, Vikas; Lin, Ai-Ling

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals' memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.

  1. Both left and right posterior parietal activations contribute to compensatory processes in normal aging

    Science.gov (United States)

    Huang, Chih-Mao; Polk, Thad A.; Goh, Joshua O.; Park, Denise C.

    2012-01-01

    Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging. PMID:22063904

  2. The Impact of Age and Cognitive Reserve on Resting-State Brain Connectivity

    Directory of Open Access Journals (Sweden)

    Jessica I. Fleck

    2017-12-01

    Full Text Available Cognitive reserve (CR is a protective mechanism that supports sustained cognitive function following damage to the physical brain associated with age, injury, or disease. The goal of the research was to identify relationships between age, CR, and brain connectivity. A sample of 90 cognitively normal adults, ages 45–64 years, had their resting-state brain activity recorded with electroencephalography (EEG and completed a series of memory and executive function assessments. CR was estimated using years of education and verbal IQ scores. Participants were divided into younger and older age groups and low- and high-CR groups. We observed greater left- than right-hemisphere coherence in younger participants, and greater right- than left-hemisphere coherence in older participants. In addition, greater coherence was observed under eyes-closed than eyes-open recording conditions for both low-CR and high-CR participants, with a more substantial difference between recording conditions in individuals high in CR regardless of age. Finally, younger participants low in CR exhibited greater mean coherence than younger participants high in CR, whereas the opposite pattern was observed in older participants, with greater coherence in older participants high in CR. Together, these findings suggest the possibility of a shift in the relationship between CR and brain connectivity during aging.

  3. The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity

    Directory of Open Access Journals (Sweden)

    Natalie M. Zahr

    2018-03-01

    Full Text Available As successfully treated individuals with Human Immunodeficiency Virus (HIV-infected age, cognitive and health challenges of normal aging ensue, burdened by HIV, treatment side effects, and high prevalence comorbidities, notably, Alcohol Use Disorders (AUD and Hepatitis C virus (HCV infection. In 2013, people over 55 years old accounted for 26% of the estimated number of people living with HIV (~1.2 million. The aging brain is increasingly vulnerable to endogenous and exogenous insult which, coupled with HIV infection and comorbid risk factors, can lead to additive or synergistic effects on cognitive and motor function. This paper reviews the literature on neuropsychological and in vivo Magnetic Resonance Imaging (MRI evaluation of the aging HIV brain, while also considering the effects of comorbidity for AUD and HCV.

  4. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys.

    Science.gov (United States)

    Molina, D Kimberley; DiMaio, Vincent J M

    2012-12-01

    Organomegaly can be a sign of disease and pathologic abnormality, although standard tables defining organomegaly have yet to be established and universally accepted. This study was designed to address the issue and to determine a normal weight for the major organs in adult human males. A prospective study of healthy men aged 18 to 35 years who died of sudden, traumatic deaths was undertaken. Cases were excluded if there was a history of medical illness including illicit drug use, if prolonged medical treatment was performed, if there was a prolonged period between the time of injury and death, if body length and weight could not be accurately assessed, or if any illness or intoxication was identified after gross and microscopic analysis including evidence of systemic disease. Individual organs were excluded if there was significant injury to the organ, which could have affected the weight. A total of 232 cases met criteria for inclusion in the study during the approximately 6-year period of data collection from 2005 to 2011. The decedents had a mean age of 23.9 years and ranged in length from 146 to 193 cm, with a mean length of 173 cm. The weight ranged from 48.5 to 153 kg, with a mean weight of 76.4 kg. Most decedents (87%) died of either ballistic or blunt force (including craniocerebral) injuries. The mean weight of the brain was 1407 g (range, 1070-1767 g), that of the liver was 1561 g (range, 838-2584 g), that of the spleen was 139 g (range, 43-344 g), that of the right lung was 445 g (range, 185-967 g), that of the left lung was 395 g (range, 186-885 g), that of the right kidney was 129 g (range, 79-223 g), and that of the left kidney was 137 g (range, 74-235 g). Regression analysis was performed and showed that there were insufficient associations between organ weight and body length, body weight, and body mass index to allow for predictability. The authors, therefore, propose establishing a reference range for organ weights in men, much like those in use

  5. A brain network processing the age of faces.

    Directory of Open Access Journals (Sweden)

    György A Homola

    Full Text Available Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

  6. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Shawn M. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lockhart, Samuel N. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Baker, Suzanne L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging; Jagust, William J. [Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging

    2017-03-22

    Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.

  7. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain

    NARCIS (Netherlands)

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia

  8. Brain-Based Teaching in the Digital Age

    Science.gov (United States)

    Sprenger, Marilee

    2010-01-01

    In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

  9. Obesity, dyslipidemia and brain age in first-episode psychosis

    Czech Academy of Sciences Publication Activity Database

    Kolenic, M.; Franke, K.; Hlinka, Jaroslav; Matějka, M.; Čapková, J.; Pausova, Z.; Uher, R.; Alda, M.; Španiel, F.; Hájek, T.

    2018-01-01

    Roč. 99, April (2018), s. 151-158 ISSN 0022-3956 Grant - others:GA MZd(CZ) NV16-32791A; GA MŠk(CZ) LO1611 Institutional support: RVO:67985807 Keywords : BrainAGE score * Dyslipidemia * First-episode psychosis * Obesity * Overweight * Schizophrenia Impact factor: 4.183, year: 2016

  10. Heterogeneity of cognitive aging in Brazilian normal elderls

    Directory of Open Access Journals (Sweden)

    Maria Paula Foss

    Full Text Available Abstract With aging, several cognitive skills inevitably decline. However, cognitive losses do not occur homogenously in all elderly people, differing in number and severity of affected cognitive functions. These differences could be exacerbated by socioeconomic differences in a developing country like Brazil. Objectives: to characterize the cognitive functioning of healthy elderly subjects whose socioeconomic conditions differ to those of other studies. Methods: 60 elderly subjects with a mean age of 68 years, 43 women and 17 men, and mean schooling of 7.1 years, were studied. The cognitive function of this group was assessed using the following neuropsychological tests: Mattis Dementia Rating Scale (MDRS, Stroop Test, Verbal Fluency, Wisconsin Card Sorting Test (WCST, Rey Complex Figure, Vocabulary - Wais - III, Logical Memory (WMS-R, Visual Reproduction (WMS-R, and Rey Auditory-Verbal Learning Test (RAVLT. The neuropsychological data were submitted to Multivariate cluster analysis using SAS - Proc Cluster software and the complete binding hierarchical method. Results: Variability was found allowing classification of the studied group into 4 clusters of individuals who had above-average (C1, average (C3 and C4 and below average (C2 performance. Schooling determined the results obtained, with less educated subjects showing poorer performance than higher-educated subjects. Conclusions: Significant differences in the process of cognitive aging were detected on neuropsychological tests in this group of healthy elderly from the developing country of Brazil, where socioeconomic differences may exacerbate cognitive differences among older adults.

  11. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    Science.gov (United States)

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  13. Intrinsic brain connectivity related to age in young and middle aged adults.

    Science.gov (United States)

    Hampson, Michelle; Tokoglu, Fuyuze; Shen, Xilin; Scheinost, Dustin; Papademetris, Xenophon; Constable, R Todd

    2012-01-01

    Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  14. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  15. Evolution of the aging brain transcriptome and synaptic regulation.

    Directory of Open Access Journals (Sweden)

    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  16. Computed tomography of the dog's brain: normal aspects and anatomical correlation

    International Nuclear Information System (INIS)

    Lorigados, C.A.B.; Pinto, A.C.B.F.

    2013-01-01

    Normal tomographic images of dog's heads were obtained, aimed to familiarize them with the normal aspects of the brain and correlate these findings with the relevant anatomy of the region studied. Several anatomical structures, such as the parenchyma of the frontal, parietal, temporal and occipital lobes, the longitudinal fissure, the ventricular system, the cerebellum, the olfactory bulb, the corpus callosum, diencephalon, the pons, the medulla oblongata and the chiasmatic sulcus were directly identified or were related to neighboring structures which helped in their identification. (author)

  17. Neuron-astrocyte signaling is preserved in the aging brain.

    Science.gov (United States)

    Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

    2017-04-01

    Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

  18. Nourish Your Brain

    Science.gov (United States)

    ... does your brain. You can’t stop normal cognitive decline, just as you can’t stop other parts of normal aging. However, you can maintain your body and brain health by making healthy choices about your lifestyle, diet, ...

  19. CT measurement of age-related brain atrophy by two-dimensional measurement with a digitizer

    International Nuclear Information System (INIS)

    Kitani, Mitsuhiro; Kobayashi, Shotai; Yamaguchi, Shuhei; Katsube, Tomoko; Okada, Kazunori; Murata, Akihiro; Tsunematsu, Tokugoro

    1984-01-01

    Various methods of the CT measurement of brain atrophy have been reported. The cranio-ventricular indices (CVI) are most popular, but these indices cannot be used for cortical atrophy. Recently, the computerized three-dimensional CT measurement of the cerebral volume has seemed a reasonable method, but a special computer system is required. The two-dimensional CT measurement of the ventricular system with a tracing method on the computer display or with planimetry has been reported, but it seems far from useful as a routine clinical CT-measurement method. We have here proposed a new method for the two-dimensional CT measurement of brain atrophy using a digitizer connected with a personal computer (Fig. 2). This system is simple, accurate, and economical. We calculated the ventricular area index (VAI) and the brain-atrophy index (BAI) as is shown in Fig. 3. Using this method, we studied age-related brain atrophy in 100 normal subjects (14-90 years) and compared the results with conventional cranio-ventricle indices. Results: 1) There were significant correlations between age and all the indices (CVI, VAI and BAI), but of these indices BAI showed the best correlation (the simple correlation coefficient was -0.67; the partial correlation coefficient was 0.38). 2) A significant acceleration of the brain atrophy from the age of 60 was observed by BAI and VAI. 3) It is suggested that the brain atrophy measured by BAI and VAI might begin earlier in men than in women. 4) A multiregression analysis of these indices to age showed the better contributional rate of the multiple correlation in VAI and BAI (52%) than that of CVI (32.6%). Conclusion: The two-dimensional CT measurement method using a digitizer is practically useful, and VAI and BAI may be more sensitive indices for brain atrophy than the conventional CVI. (author)

  20. The effect of gaze direction on sound localization in brain-injured and normal adults.

    Science.gov (United States)

    Lie, Eunhui; Branch Coslett, H

    2006-01-01

    This study examined the effects of eye position on sound localization in normal and brain lesion subjects. On the assumption that cerebral lesions may disrupt the representation of or attention to auditory space in the contralesional hemispace, we predicted that subjects with brain lesions would be less accurate in localizing sounds in the contralesional hemispace. In Experiment 1 we showed that gazing to the midline subjects with brain lesions were indeed impaired in localizing sounds in the contralesional hemispace. On the assumption that spatial attention is deployed at the site to which gaze is directed, we predicted that sound localization would be better on the side to which subjects directed their gaze. In Experiment 2, brain lesion subjects performed significantly better in the contralesional hemispace when they directed gaze to that hemispace. This improvement was accompanied by deterioration of performance in the ipsilesional hemispace. When subjects directed gaze to the ipsilesional hemispace, performance in the contralesional hemispace was further impaired. The effect of gaze was also observed in normal subjects in Experiments 2 and 3, independently of response mode (verbal versus pointing responses). These findings are consistent with the hypothesis that sound location may be mapped in eye-centered coordinates and that directing gaze to one hemispace reduces attentional allocation to the other hemispace.

  1. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

    Science.gov (United States)

    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. DNA damage in the oligodendrocyte lineage and its role in brain aging.

    Science.gov (United States)

    Tse, Kai-Hei; Herrup, Karl

    2017-01-01

    Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain. As in neurons, unrepaired DNA damage accumulates in the postmitotic oligodendrocyte genome during normal aging, and indeed may be one of the upstream causes of cellular aging - a fact well illustrated by myelin co-morbidity in premature aging syndromes arising from deficits in DNA repair enzymes. The clinical and experimental evidence from Alzheimer's disease, progeroid syndromes, ataxia-telangiectasia and other conditions strongly suggest that oligodendrocytes may in fact be uniquely vulnerable to oxidative DNA damage. If this damage remains unrepaired, as is increasingly true in the aging brain, myelin gene transcription and oligodendrocyte differentiation is impaired. Delineating the relationships between early myelin loss and DNA damage in brain aging will offer an additional dimension outside the neurocentric view of neurodegenerative disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions.

    Science.gov (United States)

    Di Benedetto, Svetlana; Müller, Ludmila; Wenger, Elisabeth; Düzel, Sandra; Pawelec, Graham

    2017-04-01

    It is widely accepted that the brain and the immune system continuously interact during normal as well as pathological functioning. Human aging is commonly accompanied by low-grade inflammation in both the immune and central nervous systems, thought to contribute to many age-related diseases. This review of the current literature focuses first on the normal neuroimmune interactions occurring in the brain, which promote learning, memory and neuroplasticity. Further, we discuss the protective and dynamic role of barriers to neuroimmune interactions, which have become clearer with the recent discovery of the meningeal lymphatic system. Next, we consider age-related changes of the immune system and possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. We survey the major immunomodulators and neuroregulators in the aging brain and their highly tuned dynamic and reciprocal interactions. Finally, we consider our current understanding of how physical activity, as well as a combination of physical and cognitive interventions, may mediate anti-inflammatory effects and thus positively impact brain aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Brain herniation in a patient with apparently normal intracranial pressure: a case report

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    Dahlqvist Mats B

    2010-08-01

    Full Text Available Abstract Introduction Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension. Case presentation An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg. Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover. Conclusions Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation.

  5. Effect of 60Co-irradiation on normal and low protein diet fed rat brain

    International Nuclear Information System (INIS)

    Hasan, S.S.; Habibullah, M.

    1980-01-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

  6. Clinical study on brain tumors in the aged

    International Nuclear Information System (INIS)

    Teramoto, Akira; Manaka, Shinya; Takakura, Kintomo

    1981-01-01

    In order to investigate the clinical features and the prognosis of brain tumors in the aged, 132 cases over 60 years of age were studied from the consecutive series of 1,793 brain tumors in the University of Tokyo Hospital (1963 - 1979). The incidence of brain tumors in the aged was 7.4% on the whole, while it showed a significant increase from 4.8% (1960's) to 11.5% (the later half of 1970's). Histologically, meningiomas were the most common tumors (26%), followed by neurinomas (17%), pituitary adenomas (16%) and metastatic tumors (15%). Malignant gliomas were found more frequently than benign ones. There were more meningiomas as age advanced. The proportion and the number of meningioma cases has obviously increased in recent years when CT scanners became available. Symptoms of intracranial hypertention were found less frequently in aged patients although they were still common in cases of glioblastomas. The duration from onset to surgery was relatively long, especially in cases of neurinomas and pituitary adenomas. Two cases of astrocytomas belonged to the category of silent gliomas. Overall operative mortality rate was 10.6%, while it showed a marked decrease to 4.7% in the 1970's. Five-year survival rates were as follows: meningiomas (58%), pituitary adenomas (70%), neurinomas (80%), glioblastomas (20%) and astrocytomas (25%). As for functional prognoses, 30% of the patients showed poor states on ADL, mostly because of residual psychic disorders. (author)

  7. Aging effects on regional brain structural changes in schizophrenia.

    Science.gov (United States)

    Nenadić, Igor; Sauer, Heinrich; Smesny, Stefan; Gaser, Christian

    2012-06-01

    Although mostly conceptualized as a neurodevelopmental disorder, there is an increasing interest in progressive changes of cognitive deficits and brain structure and function in schizophrenia across the life span. In this study, we investigated age-related changes in regional gray matter using voxel-based morphometry in a sample of 99 patients (age range 18-65 years) with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia and 113 healthy controls (age range 19-59 years) using a cross-sectional design. We found steeper age-related decline in gray matter in patients in a cluster comprising the left superior temporal cortex and adjacent inferior parietal lobule. We then divided the schizophrenia sample in 3 subgroups based on a 3-factor model of psychopathology ratings. Age-related changes were markedly different in each of the 3 subgroups (compared with healthy controls). While patients with predominantly paranoid symptoms showed stronger age-related progression in the left superior temporal cortex and right inferior frontal gyrus, those of the disorganized subgroup had stronger gray matter loss in the left lateral cerebellum, while the predominantly negative subgroup showed minor effects in the left superior temporal gyrus. Our findings show that differences in brain structural changes associated with aging diverge between schizophrenia patients and healthy subjects and that different subgroups within a patient sample might be at higher risk of age-related regional gray matter loss.

  8. Age prediction on the basis of brain anatomical measures.

    Science.gov (United States)

    Valizadeh, S A; Hänggi, J; Mérillat, S; Jäncke, L

    2017-02-01

    In this study, we examined whether age can be predicted on the basis of different anatomical features obtained from a large sample of healthy subjects (n = 3,144). From this sample we obtained different anatomical feature sets: (1) 11 larger brain regions (including cortical volume, thickness, area, subcortical volume, cerebellar volume, etc.), (2) 148 cortical compartmental thickness measures, (3) 148 cortical compartmental area measures, (4) 148 cortical compartmental volume measures, and (5) a combination of the above-mentioned measures. With these anatomical feature sets, we predicted age using 6 statistical techniques (multiple linear regression, ridge regression, neural network, k-nearest neighbourhood, support vector machine, and random forest). We obtained very good age prediction accuracies, with the highest accuracy being R 2  = 0.84 (prediction on the basis of a neural network and support vector machine approaches for the entire data set) and the lowest being R 2  = 0.40 (prediction on the basis of a k-nearest neighborhood for cortical surface measures). Interestingly, the easy-to-calculate multiple linear regression approach with the 11 large brain compartments resulted in a very good prediction accuracy (R 2  = 0.73), whereas the application of the neural network approach for this data set revealed very good age prediction accuracy (R 2  = 0.83). Taken together, these results demonstrate that age can be predicted well on the basis of anatomical measures. The neural network approach turned out to be the approach with the best results. In addition, it was evident that good prediction accuracies can be achieved using a small but nevertheless age-representative dataset of brain features. Hum Brain Mapp 38:997-1008, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Physiological and biochemical effects of 17β estradiol in aging female rat brain.

    Science.gov (United States)

    Kumar, Pardeep; Taha, Asia; Kale, R K; Cowsik, S M; Baquer, Najma Zaheer

    2011-07-01

    Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs

    DEFF Research Database (Denmark)

    Dekker, Simone E; Sillesen, Martin; Bambakidis, Ted

    2014-01-01

    BACKGROUND: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS...... of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. RESULTS: Serum levels of aPC were greater in the NS group (203 ± 30...... pg/mL) compared with HEX (77 ± 28 pg/mL; P = .02) and FFP (110 ± 28 pg/mL; P = .09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89 ± 46 vs 37 ± 14 ng/mL; P = .035). Brain E-selectin was greater in the NS group compared with FFP (3.36 ± 0.02 vs 3.31 ± 0.01 ng/mL; P = .029...

  11. Nicotinic receptor imaging with F-18 A85380 PET in Alzheimer's disease and normal ageing

    International Nuclear Information System (INIS)

    Bottlaender, M.; Maziere, B.; Pappata, S.; Dolle, F.; Rowe, C.; Tochon-Danguy, H.; Reutens, D.; Chan, G.; Woodward, M.

    2002-01-01

    Full text: Central nicotinic acetylcholine receptors (nAChR) mediate excitatory neurotransmission and contribute to a variety of brain functions including learning and memory. Post mortem studies in patients with Alzheimer's disease have revealed losses of nAChR from the neocortex and hippocampal formation with ligand binding studies showing a reduction of over 50% compared to normal elderly brains in the temporal cortex and hippocampus (Sabbagh 1998). This is consistent with the loss of cholinergic neurones that has been well documented in this condition. Nicotinic AChR are predominantly located presynaptically on the cholinergic neurones. Consequently the ability to image and quantify these receptors may provide a measure of cholinergic loss and therefore a test for the early diagnosis of Alzheimer's disease and for monitoring therapy designed' to preserve cholinergic neurones. Aging is known to effect nAChR (Hellstrom-Lindahl 2000) so this variable must be quantified and incorporated into analysis of the scans. Nicotinic receptors also have important modulatory effects on glutamate, dopamine, serotonin and noradrenaline release and profound receptor loss has been documented in Parkinson's disease and Diffuse Lewy Body disease in addition to AD. Abnormalities in the alpha 7 subtype have been reported in schizophrenia. Imaging studies of nAChR have been hampered by the lack of a suitable tracer for in-vivo imaging. Nicotine itself labelled with carbon-11 for PET imaging has been used but has been shown to reflect regional cerebral blood flow not nAChR due to high nonspecific binding (Nyback et al, 1994). Potent nAChR ligands such as Epibatidine have been very useful for in-vitro studies but are too toxic for routine human use due to strong activation of nAChR including those in the sympathetic ganglia (A3B4 subtype). Recently, the Abbott Laboratories developed A85380 (3-[2(S)-2- azetidinylmethoxyl]pyridine) an azetidine derivative of the 3-pyridyl ethers that has

  12. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

    Directory of Open Access Journals (Sweden)

    Zhan-chi Zhang

    2015-01-01

    Full Text Available In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  13. Aging brain from a network science perspective: something to be positive about?

    Directory of Open Access Journals (Sweden)

    Michelle W Voss

    Full Text Available To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large-scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being.

  14. Exercise-related changes of networks in aging and mild cognitive impairment brain

    Directory of Open Access Journals (Sweden)

    Pei eHuang

    2016-03-01

    Full Text Available Aging and mild cognitive impairment are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer’s disease, which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. Mild cognitive impairment is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of mild cognitive impairment to Alzheimer’s disease might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat Alzheimer’s disease, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and mild cognitive impairment populations. Previous studies have found some cognitive brain networks disrupted in aging and mild cognitive impairment population, and physical exercise could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective physical exercise programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and mild cognitive impairment to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions.

  15. Prevalence of mixed pathologies in the aging brain.

    Science.gov (United States)

    Rahimi, Jasmin; Kovacs, Gabor G

    2014-01-01

    The spectrum of mixed brain pathologies expands beyond accompanying vascular pathology in brains with Alzheimer's disease-related pathology. Co-occurrence of neurodegenerative non-Alzheimer's disease-type proteinopathies is increasingly recognized to be a frequent event in the brains of symptomatic and asymptomatic patients, particularly in older people. Owing to the evolving concept of neurodegenerative diseases, clinical and neuropathological diagnostic criteria have changed during the last decades. Autopsy-based studies differ in the selection criteria and also in the applied staining methods used. The present review summarizes the prevalence of mixed brain pathologies reported in recent community-based studies. In these cohorts, irrespective of the clinical symptoms, the frequency of Alzheimer's disease-related pathology is between 19 and 67%, of Lewy body pathology is between 6 and 39%, of vascular pathologies is between 28 and 70%, of TDP-43 proteinopathy is between 13 and 46%, of hippocampal sclerosis is between 3 and 13% and, finally, of mixed pathologies is between 10 and 74%. Some studies also mention tauopathies. White-matter pathologies are not discussed specifically in all studies, although these lesions may be present in more than 80% of the aging brains. In summary, community-based neuropathology studies have shown that complex constellations of underlying pathologies may lead to cognitive decline, and that the number of possible combinations increases in the aging brain. These observations have implications for the prediction of the prognosis, for the development of biomarkers or therapy targets, or for the stratification of patient cohorts for genome-wide studies or, eventually, for therapy trials.

  16. A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation.

    Science.gov (United States)

    Saugstad, L F

    1999-10-19

    The planum temporale (PT) bias, PT leftward, PT symmetry, and PT rightward reversal and sidedness preference, consistent right-handedness, ambilaterality, and consistent left-handedness are placed on a continuum mirroring the normal variation in rate of brain maturation. Maturational rate declines as we pass from PT leftward bias and consistent right-handedness to PT reversal and consistent left-handedness. Concomitantly, we expect an increased prevalence of males due to their pubertal age being about 2 years later than that of females, and a shift in cognitive profile from higher verbal scores than performance scores on the WAIS to higher performance than verbal scores. Three disorders fulfilling the criteria of late CNS maturation apart from the corresponding cognitive profile were studied: infantile autism (IA), schizophrenia (S), and developmental dyslexia (DD). These disorders have in common deficits in cognition, perception, and somatomotor function. The deficits range from an arrest in brain development (which is evident in infancy superimposed on late maturation in IA) to overall delayed brain and somatic development in S (culminating in postpubertal psychotic episodes and persistent and generalized residual deficits). Finally, reading inability, problems in perception (vision and hearing) and in motor coordination, particularly between the two hemispheres, characterize DD. Enhancing brain maturation and the prevalence of 'normal' cerebral asymmetry--laterality is preferable if we want to reduce the risk of developing the above-mentioned disorders. It is suggested that in the past environmental challenges have favored early maturation, with its abundant neuronal population, arborization and excessive density of synapses and cerebral excitability which has powered evolution through the mechanism of natural selection. Early maturation is obtainable through optimal nutrition, including a satisfactory amount of marine fat (PUFA), before and during pregnancy and

  17. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  18. Computed tomographic features of the feline brain change with advancing age?

    Directory of Open Access Journals (Sweden)

    Viviam R. Babicsak

    2015-12-01

    Full Text Available Abstract: A better understanding of normal or expected encephalic changes with increasing age in cats is needed as a growing number of these animals is attended in veterinary clinics, and imaging data referring to normal age-associated changes are extremely scarce in the literature. The objective of this study was to identify age-related changes in feline brain using CT imaging. Fifteen non-brachycephalic healthy cats with age between 1 to 6 years (adult group and others over 12 years (geriatric group were submitted to CT scan of the brain. Statistically significant differences were found between the groups for the ability to identify the left lateral ventricle and for falx cerebri calcification, both identified in a greater number of cats of the geriatric group. A significantly higher mean width of the third ventricle was also detected in geriatric animals. There were no statistically significant differences between lateral ventricular dimensions and encephalic parenchymal attenuation on pre and post-contrast CT phases. The results of the present study show an increase in the incidence of falx cerebri calcification and a third ventricular dilatation with advancing age in cats. Future researches using MRI scanners and a greater quantity of cats are needed in order to identify supplementary age-related changes.

  19. Towards adapting a normal patient database for SPECT brain perfusion imaging

    International Nuclear Information System (INIS)

    Smith, N D; Soleimani, M; Mitchell, C N; Holmes, R B; Evans, M J; Cade, S C

    2012-01-01

    Single-photon emission computerized tomography (SPECT) is a tool which can be used to image perfusion in the brain. Clinicians can use such images to help diagnose dementias such as Alzheimer's disease. Due to the intrinsic stochasticity in the photon imaging system, some form of statistical comparison of an individual image with a 'normal' patient database gives a clinician additional confidence in interpreting the image. Due to the variations between SPECT camera systems, ideally a normal patient database is required for each individual system. However, cost or ethical considerations often prohibit the collection of such a database for each new camera system. Some method of adapting existing normal patient databases to new camera systems would be beneficial. This paper introduces a method which may be regarded as a 'first-pass' attempt based on 2-norm regularization and a codebook of discrete spatially stationary convolutional kernels. Some preliminary illustrative results are presented, together with discussion on limitations and possible improvements

  20. A comparision of Brain-Behavioral Systems in patients with multiple sclerosis and normal individuals

    Directory of Open Access Journals (Sweden)

    kobra Moradi

    2016-05-01

    Full Text Available Background: The aim of this study was to compare   Brain-Behavioral Systems in patient with multiple sclerocis (MS and normal individuals. Materials and Methods: This research was a post facto comparative study, subjects included  healthy persons and all patients with MS, which in summer and autumn 2013 referred to neurologists in the Lorestan province. Of the population using as samples, 117 cases (75 patients and 42 normal subjects were selected, then Gray- Wilson Personality Questionnaire was completed for them. To analyze the data, multivariate analysis of variance (MANOVA test  was used to compare the two groups. Results: The results showed, in BAS scales, people with MS had significantly lower scores than normal subjects Conclusion: What comes from findings indicates that a low score in behavioral activation as a pathological factors in chronic diseases such as MS is concerned and is in need of psychological treatment.

  1. Application of 3.0T magnetic resonance spectroscopy imaging in the evaluation on the development of normal brain white matter in infants and young children

    Directory of Open Access Journals (Sweden)

    Wen-li XU

    2014-01-01

    Full Text Available Objective To calculate the radios of peak area of proton magnetic resonance spectroscopy metabolites in brain white matter of normal infants and young children, to observe the features of metabolite spectra, and to explore the relations between their ratio with age. Methods The peak areas of metabolites, including N-acetyl aspartate (NAA, choline (Cho, creatine (Cr, and their ratio of NAA/Cho, NAA/Cr, Cho/Cr, in paraventricular white matter of 180 normal infants and young children with different ages as evaluated by multi-voxel proton magnetic resonance spectroscopy. Results In paraventricular white matter, spectrum of NAA increased, and that of Cho decreased gradually, while both of them were stabilized at 2 years old. Cr was increased obviously within 3 months, and stabilized after 4 months. Significant differences were found in ratio of different metabolites in paraventricular white matter in different ages (P<0.05. The ratios of NAA/Cho and NAA/Cr in paraventricular white mater were positively correlated with age (r=0.741, r=0.625, while that of Cho/Cr was negatively correlated with age (r=–0.552, P<0.05. Conclusion The ratios of different metabolites are different in brain white matter in infants of different ages. Metabolites concentrations in brain white matter are correlated to some extent with age, which may provide a diagnostic criterion for evaluation of normal brain development and abnormal brain metabolism. DOI: 10.11855/j.issn.0577-7402.2013.12.05

  2. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Mariarita Romanucci

    2015-01-01

    Full Text Available Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS and Heat Shock Proteins (HSPs, in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  3. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders.

    Science.gov (United States)

    Romanucci, Mariarita; Della Salda, Leonardo

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  4. MRI study of the brain in aged volunteers

    International Nuclear Information System (INIS)

    Kasahara, Hiroo; Tanno, Munehiko; Yamada, Hideo; Endoh, Kazuo; Kobayashi, Mitsuru; Karasawa, Akihide.

    1993-01-01

    In order to characterize age-related and chronological changes of the brain, longitudinal studies of aged volunteers were conducted using computed tomography since 1982. The present paper discusses correlations between brain function and findings of MR images which were obtained using a 1.5 T superconductive MR instrument since 1989. A total of 118 volunteers aged 60 to 88 years old with a mean age of 75.0±6.7 participated in the study, which consisted of MRI, EEG recording, the Benton Visual Retention Test and a medical interview. Subjects with a past history or clinical evidence of CVD, head trauma or dementia were excluded from the study. Incidence of T 2 high signal intensity lesions increased with age. Some showing T 1 low signal intensity in the same lesion were considered to be lacunar infarction, over all incidence of which was 24.6%. Numbers of correct responses on the BVRT showed a negative correlation with numbers of T 2 high signal intensity lesions. Although the aged volunteers in the present study could achieve all activity of daily living without any trouble, high cortical function evaluated by visuoperceptual performance of BVRT was somewhat disturbed in participants with multiple T 2 high signal intensity lesions. Brain atrophy seems to be more advanced in groups with T 2 hyper intensity lesions than in the group without them. These findings may support the notion that T 2 high signal intensity lesions are not merely an index of aging but pathologic lesions accompanied with senescence, although further studies including clinico-pathological correlation are necessary to establish this concept. (author)

  5. Effects of aging and dietary n-3 fatty acids on rat brain phospholipids: focus on plasmalogens.

    Science.gov (United States)

    André, A; Juanéda, P; Sébédio, J L; Chardigny, J M

    2005-08-01

    The aging brain undergoes modifications in the lipid composition of cell membranes and especially in plasmalogens. These phospholipids represent between one-half and two-thirds of the ethanolamine phospholipids in the brain. They are known to facilitate membrane fusion and act as endogenous antioxidants. During normal aging and in some pathological conditions, plasmalogen and DHA levels fall. In this context, we aimed to evaluate the influence of n-3 FA intake on plasmalogens in the brain during aging. Littermates from two generations of n-3-deficient rats were fed an n-3-deficient diet or an equilibrated diet containing either alpha-linolenic acid alone (alpha-LNA) or with two doses of DHA (0.3 or 0.6% w/w). After weaning, 9 mon of diet, or 21 mon of diet, plasmalogen levels were assessed, and the sn-2 substitutions of plasmenylethanolamines were analyzed in the cortex, striatum, and hippocampus. Our results showed that plasmalogen contents were not influenced by the diet. Plasmalogen levels were significantly decreased in aged rats compared with adults, whereas DHA levels increased in the hippocampus and remained stable in the cortex and striatum. DHA levels were significantly and similarly increased in total phospholipids and especially in plasmenylethanolamines after 9 mon of diet containing alpha-LNA alone or combined with DHA. This study showed that each structure sustained specific age-induced modifications. Dietary n-3 FA may not oppose the physiological decrease in brain plasmalogen levels during aging. Moreover, alpha-LNA appears to be equally as potent as preformed DHA at replacing DHA in the brain of our rat model.

  6. Distinct Brain and Behavioral Benefits from Cognitive versus Physical Training: A Randomized Trial in Aging Adults

    Directory of Open Access Journals (Sweden)

    Sandra Bond Chapman

    2016-07-01

    Full Text Available Insidious declines in normal aging are well established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT versus physical training (PT on cognition and brain function in adults 56–75 years. Sedentary participants (N=36 were randomized to either CT or PT group for 3 hours/week over 12 weeks. They were assessed at baseline, mid-training and post-training using neurocognitive, MRI and physiological measures. The CT group improved on executive function whereas PT group’s memory was enhanced. Uniquely deploying cerebral blood flow (CBF and cerebral vascular reactivity (CVR MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex. Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

  7. Morphometric and volumetric study of caudate and putamen nuclei in normal individuals by MRI: Effect of normal aging, gender and hemispheric differences

    International Nuclear Information System (INIS)

    Abedelahi, Ali; Hasanzadeh, Hadi; Hadizadeh, Homaioon; Joghataie, Mohammad Taghi

    2013-01-01

    The aim of this study was to determine age, gender, and hemispheric differences in the volume of the human neostriatum (striatum) nucleus in healthy humans. This study was performed on 120 normal human subjects (60 males, 60 females, right-handed) 15–65 years old, divided into two groups: young (<40 yrs) and old (=≥40 yrs). Sectional brain images were obtained via magnetic resonance imaging (MRI), analyzed and processed using the Image-J software, and the striatum volume was calculated using the Cavalieri’s principle, retrospectively. The analyses revealed bilateral age-related shrinkage of the putamen in both genders and the putamen and caudate nucleus were significantly smaller in older than in younger subjects (P-value <0.001). The age-related shrinkage of the caudate and putamen nucleus in men and women was about 5%, 5% and 4%, 4%, respectively, and there were statistically significant volume differences between males and females (P-value <0.05). In both genders, a significant rightward asymmetry was observed in the caudate and putamen nucleus (3.89%, 4.21% in men and 4.51%, 3.32% in women). Bilateral age-related shrinkage and rightward asymmetry of the striate nucleus was found in healthy adults and there were significant volume differences between men and women. Obtained results provide useful baseline data on age and gender-related changes of the volume of the striatum

  8. Elemental composition of 'normal' and Alzheimer brain tissue by INA and PIXE analyses

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of 'normal' and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer's Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 'normal' and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author)

  9. Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain

    International Nuclear Information System (INIS)

    Bouchet, Audrey; Lemasson, Benjamin; Christen, Thomas; Potez, Marine; Rome, Claire; Coquery, Nicolas; Le Clec’h, Céline; Moisan, Anaick; Bräuer-Krisch, Elke; Leduc, Géraldine; Rémy, Chantal; Laissue, Jean A.; Barbier, Emmanuel L.; Brun, Emmanuel; Serduc, Raphaël

    2013-01-01

    Purpose: Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. Methods: Tissue responses to MRT (two orthogonal arrays (2 × 400 Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR S O 2 ) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. Results: In tumors, MR S O 2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR S O 2 , although vessel inter-distances increased slightly. Conclusion: We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia

  10. Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

    Directory of Open Access Journals (Sweden)

    Laura Moreno-López

    Full Text Available INTRODUCTION: Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. METHODS: Fifty-two adolescents (16 with normal weight and 36 with excess weight were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM was used to assess possible between-group differences in regional gray matter (GM and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices and motivation/impulse control (hippocampus, prefrontal cortex. RESULTS: Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. CONCLUSION: Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

  11. Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

    Science.gov (United States)

    Coupé, Pierrick; Catheline, Gwenaelle; Lanuza, Enrique; Manjón, José Vicente

    2017-11-01

    There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Fatty Acids, Antioxidants and Physical Activity in Brain Aging

    Directory of Open Access Journals (Sweden)

    Hércules Rezende Freitas

    2017-11-01

    Full Text Available Polyunsaturated fatty acids and antioxidants are important mediators in the central nervous system. Lipid derivatives may control the production of proinflammatory agents and regulate NF-κB activity, microglial activation, and fatty acid oxidation; on the other hand, antioxidants, such as glutathione and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in the brains of the young and the aged in degenerative diseases such as Alzheimer’s and Parkinson’s, and during brain aging due to adiposity- and physical inactivity-mediated metabolic disturbances, chronic inflammation, and oxidative stress. Through a literature review, we aimed to highlight recent data on the role of adiposity, fatty acids, antioxidants, and physical inactivity in the pathophysiology of the brain and in the molecular mechanisms of senescence. Data indicate the complexity and necessity of endogenous/dietary antioxidants for the maintenance of redox status and the control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, influencing feeding behavior, neural plasticity, and memory during aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and requires additional effort from researchers, clinicians, and nutritionists in the field.

  13. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

    Science.gov (United States)

    Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

    2017-03-01

    Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

  14. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation. © 2012 European Sleep Research Society.

  15. Human brain networks in physiological aging: a graph theoretical analysis of cortical connectivity from EEG data.

    Science.gov (United States)

    Vecchio, Fabrizio; Miraglia, Francesca; Bramanti, Placido; Rossini, Paolo Maria

    2014-01-01

    Modern analysis of electroencephalographic (EEG) rhythms provides information on dynamic brain connectivity. To test the hypothesis that aging processes modulate the brain connectivity network, EEG recording was conducted on 113 healthy volunteers. They were divided into three groups in accordance with their ages: 36 Young (15-45 years), 46 Adult (50-70 years), and 31 Elderly (>70 years). To evaluate the stability of the investigated parameters, a subgroup of 10 subjects underwent a second EEG recording two weeks later. Graph theory functions were applied to the undirected and weighted networks obtained by the lagged linear coherence evaluated by eLORETA on cortical sources. EEG frequency bands of interest were: delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). The spectral connectivity analysis of cortical sources showed that the normalized Characteristic Path Length (λ) presented the pattern Young > Adult>Elderly in the higher alpha band. Elderly also showed a greater increase in delta and theta bands than Young. The correlation between age and λ showed that higher ages corresponded to higher λ in delta and theta and lower in the alpha2 band; this pattern reflects the age-related modulation of higher (alpha) and decreased (delta) connectivity. The Normalized Clustering coefficient (γ) and small-world network modeling (σ) showed non-significant age-modulation. Evidence from the present study suggests that graph theory can aid in the analysis of connectivity patterns estimated from EEG and can facilitate the study of the physiological and pathological brain aging features of functional connectivity networks.

  16. Normal value of mucosal thickness of paranasal sinuses, as seen on brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Byung Kook; Shin, Sang Bum; Cheon, Bong Jin; Kim, Seong Min; Kim, Jong Min; Oh, Kyung Seung; Jung, Gyoo Sik; Huh, Jin Do; Joh, Young Duk [Kosin Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-02-01

    To evaluate incidentally observed thickened mucosa of paranasal sinuses on brain MRI of patients without evidence of sinusitis. We reviewed brain MRI of 82 adults aged over 20; 45 were males and 37 were females. Brain axial MRI was obtained from the hard palate with 8mm thickness and 2mm gap. The mucosal thickness of incidentally observed paranasal sinuses seen on brain MRI was measured at the mostly thickened portion by T2- and T1-weighted images. The mean mucosal thickness at the most thickened portion of paranasal sinuses, regardless of their location was 3.5mm with S.D. of 1.5mm. The mucosal thickening was observed more commonly in maxillary (79 patients, mean 3.0mm, S.D. 1.4mm) and ethmoid sinuses (80 patients, mean 2.7mm, S.D. 1.1mm) than in sphenoid (39 patients, mean 1.6mm, S.D. 1.4mm) or frontal sinuses (38 patients, mean 1.9mm, S.D. 1.4mm). Mucosal thickening of up to 6.5mm was a common finding on brain MRI of patients without evidence of sinusitis; accuracy was 95%.

  17. The whole-brain N-acetylaspartate correlates with education in normal adults.

    Science.gov (United States)

    Glodzik, Lidia; Wu, William E; Babb, James S; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U; Gass, Achim; Gonen, Oded

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

    Science.gov (United States)

    Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

    2017-11-15

    Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

  19. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    International Nuclear Information System (INIS)

    Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-01-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

  20. Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain

    Directory of Open Access Journals (Sweden)

    Krysti L. Todd

    2018-01-01

    Full Text Available Ventriculomegaly (expansion of the brain’s fluid-filled ventricles, a condition commonly found in the aging brain, results in areas of gliosis where the ependymal cells are replaced with dense astrocytic patches. Loss of ependymal cells would compromise trans-ependymal bulk flow mechanisms required for clearance of proteins and metabolites from the brain parenchyma. However, little is known about the interplay between age-related ventricle expansion, the decline in ependymal integrity, altered periventricular fluid homeostasis, abnormal protein accumulation and cognitive impairment. In collaboration with the Baltimore Longitudinal Study of Aging (BLSA and Alzheimer’s Disease Neuroimaging Initiative (ADNI, we analyzed longitudinal structural magnetic resonance imaging (MRI and subject-matched fluid-attenuated inversion recovery (FLAIR MRI and periventricular biospecimens to map spatiotemporally the progression of ventricle expansion and associated periventricular edema and loss of transependymal exchange functions in healthy aging individuals and those with varying degrees of cognitive impairment. We found that the trajectory of ventricle expansion and periventricular edema progression correlated with degree of cognitive impairment in both speed and severity, and confirmed that areas of expansion showed ventricle surface gliosis accompanied by edema and periventricular accumulation of protein aggregates, suggesting impaired clearance mechanisms in these regions. These findings reveal pathophysiological outcomes associated with normal brain aging and cognitive impairment, and indicate that a multifactorial analysis is best suited to predict and monitor cognitive decline.

  1. The gender difference in the brain FDG distribution with aging

    International Nuclear Information System (INIS)

    Nakabeppu, Yoshiaki; Tanabe, Hiroaki; Jinguji, Megumi; Umanodan, Tomokazu; Nakajo, Masayuki; Nakajo, M.; Tateno, T.; Jinnouchi, S.

    2007-01-01

    The purpose of this study is to examine the change in brain fluorodeoxyglucose (FDG) distribution with aging. Subjects were 85 men and 116 women who had no mental abnormality and no evidence of cancer in the whole body FDG-positron emission tomography (PET) study for cancer checkup. The brain data were extracted from whole body data, and stratified according to the age: 30-39 (M: 10, F: 18), 40-49 (M: 11, F: 14), 50-59 (M: 10, F: 27), 60-64 (M: 11, F: 13), 65-69 (M: 11, F: 11), 70-74 (M: 11, F: 10), 75-79 (M: 13, F: 11), over 80 (M: 8, F: 12) years. Forties or more male and female stratified age groups were compared with each gender 30's age data using Statistical Parametric Mapping (SPM)2. In the man, the FDG activity of the bilateral temporal and frontal lobes decreased and the decreased domains were expanded with aging. But in the females, the decreased domains were complicated in 40-69 years old. Dynamic changes of sex hormones in the individual female menopause may affect the complicated results in the females. Further studies are needed to confirm it. (author)

  2. Age and Gender Effects On Auditory Brain Stem Response (ABR

    Directory of Open Access Journals (Sweden)

    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  3. Age-Related Sex-Specific Changes in Brain Metabolism and Morphology.

    Science.gov (United States)

    Kakimoto, Akihiro; Ito, Shigeru; Okada, Hiroyuki; Nishizawa, Sadahiko; Minoshima, Satoshi; Ouchi, Yasuomi

    2016-02-01

    With a large database, we aimed to evaluate sex-specific distinctive changes in brain glucose metabolism and morphology during normal aging using MRI and (18)F-FDG PET. A total of 963 cognitively healthy adults were included in this study. All subjects completed a medical questionnaire, took the mini-mental state examination, and underwent brain MRI and whole-body (18)F-FDG PET. The MR and PET images were statistically analyzed using 3-dimensional stereotactic surface projection. All images were corrected for whole-brain pixel value to identify the brain regions with significant changes, and regions of interest were set up with reference to Brodmann areas. We evaluated morphologic and glucose metabolic changes by cross-sectional analysis. The baseline database consisted of subjects from 30 to 40 y old, and the age-step for comparison was 5-y ranges. We also compared sex-specific differences in MR and PET images in each age group. Regarding age-related changes, in both sexes brain atrophy was observed in the lateral frontal and parietal regions and glucose hypometabolism in the medial frontal regions. There were significant differences in these parameters between the sexes; parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals 66 y or older. Our brain mapping study with a large number of reference human brain data demonstrated age-related parallel changes between morphology and metabolism in the medial frontal regions and sex-specific hypometabolism in the parietal (male) and ventrolateral prefrontal (female) cortices. These findings may suggest an aging vulnerability in sex-specific brain regions: the parietal cortex for

  4. SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Hossain, S; Hildebrand, K; Ahmad, S; Larson, D; Ma, L; Sahgal, A

    2014-01-01

    Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targets were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery

  5. Age-dependent effects of brain stimulation on network centrality

    DEFF Research Database (Denmark)

    Antonenko, Daria; Nierhaus, Till; Meinzer, Marcus

    2018-01-01

    Functional magnetic resonance imaging (fMRI) studies have suggested that advanced age may mediate the effects of transcranial direct current stimulation (tDCS) on brain function. However, studies directly comparing neural tDCS effects between young and older adults are scarce and limited to task......-related imaging paradigms. Resting-state (rs-) fMRI, that is independent of age-related differences in performance, is well suited to investigate age associated differential neural tDCS effects. Three “online” tDCS conditions (anodal, cathodal, sham) were compared in a cross-over, within-subject design, in 30...... characterized neural tDCS effects. An interaction between anodal tDCS and age group was observed. Specifically, centrality in bilateral paracentral and posterior regions (precuneus, superior parietal cortex) was increased in young, but decreased in older adults. Seed-based analyses revealed that these opposing...

  6. [Age and changes in human brain capillaries (histochemical study)].

    Science.gov (United States)

    Chertok, V M

    1985-02-01

    The vascular-capillary bed in the field 17 of the human brain cortex (from fetuses up to 86 years of age) has been studied by means of some histochemical methods to reveal alcaline phosphatase and Mg-ATPase. As demonstrate quantitative methods, active processes of the capillary bed formation in the cerebral cortex take place before 8-16 years of age. Towards the old age, the amount of the vessels with a high and moderate enzymatic activity decreases, but those with a low enzymatic activity increases. The average parameters of the optic density of the reaction product decreases respectively in the capillary wall, so does the intensity of metabolic processes, while the value of the working surface increases up to 75 years of age.

  7. Insulin Signaling-independent Activation of DAF-16 Shapes the Transcriptome during Normal Aging

    OpenAIRE

    Zhang, Yan-Ping; Liang, Chung-Yi; Hsu, Ao-Lin; Li, Shang-Tong; Zhang, Pan; Dong, Meng-Qiu; Zhao, Han-Qing

    2018-01-01

    The roles and regulatory mechanisms of transriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the exp...

  8. Age and Gender Effects on Wideband Absorbance in Adults with Normal Outer and Middle Ear Function

    Science.gov (United States)

    Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

    2015-01-01

    Purpose: This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Method: Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance…

  9. Challenges of multimorbidity of the aging brain: a critical update.

    Science.gov (United States)

    Jellinger, Kurt A; Attems, Johannes

    2015-04-01

    A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80% of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19-100%, with "pure" Alzheimer's disease (AD) in 17-72%, Lewy pathology in 6-39% (AD + Lewy disease 9-28%), vascular pathologies in 28-93% (10.7-78% "pure" vascular dementia), TDP-43 proteinopathy in 6-39%, hippocampal sclerosis in 8-1%, and mixed pathologies in 10-93%. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies

  10. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    Science.gov (United States)

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Bioactive form of resveratrol in glioblastoma cells and its safety for normal brain cells

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Shu

    2013-05-01

    Full Text Available ABSTRACTBackground: Resveratrol, a plant polyphenol existing in grapes and many other natural foods, possesses a wide range of biological activities including cancer prevention. It has been recognized that resveratrol is intracellularly biotransformed to different metabolites, but no direct evidence has been available to ascertain its bioactive form because of the difficulty to maintain resveratrol unmetabolized in vivo or in vitro. It would be therefore worthwhile to elucidate the potential therapeutic implications of resveratrol metabolism using a reliable resveratrol-sensitive cancer cells.Objective: To identify the real biological form of trans-resveratrol and to evaluate the safety of the effective anticancer dose of resveratrol for the normal brain cells.Methods: The samples were prepared from the condition media and cell lysates of human glioblastoma U251 cells, and were purified by solid phase extraction (SPE. The samples were subjected to high performance liquid chromatography (HPLC and liquid chromatography/tandem mass spectrometry (LC/MS analysis. According to the metabolite(s, trans-resveratrol was biotransformed in vitro by the method described elsewhere, and the resulting solution was used to treat U251 cells. Meanwhile, the responses of U251 and primarily cultured rat normal brain cells (glial cells and neurons to 100μM trans-resveratrol were evaluated by multiple experimental methods.Results: The results revealed that resveratrol monosulfate was the major metabolite in U251 cells. About half fraction of resveratrol monosulfate was prepared in vitro and this trans-resveratrol and resveratrol monosulfate mixture showed little inhibitory effect on U251 cells. It is also found that rat primary brain cells (PBCs not only resist 100μM but also tolerate as high as 200μM resveratrol treatment.Conclusions: Our study thus demonstrated that trans-resveratrol was the bioactive form in glioblastoma cells and, therefore, the biotransforming

  12. Development of Planning Abilities in Normal Aging: Differential Effects of Specific Cognitive Demands

    Science.gov (United States)

    Köstering, Lena; Stahl, Christoph; Leonhart, Rainer; Weiller, Cornelius; Kaller, Christoph P.

    2014-01-01

    In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of…

  13. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    International Nuclear Information System (INIS)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

    2002-01-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  14. A Long Journey into Aging, Brain Aging, and Alzheimer's Disease Following the Oxidative Stress Tracks.

    Science.gov (United States)

    Mecocci, Patrizia; Boccardi, Virginia; Cecchetti, Roberta; Bastiani, Patrizia; Scamosci, Michela; Ruggiero, Carmelinda; Baroni, Marta

    2018-01-01

    The Editors of the Journal of Alzheimer's Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal's top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer's disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2'-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci's laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research.

  15. NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION

    Science.gov (United States)

    Emblem, Kyrre; Pinho, Marco; Chandra, Vyshak; Gerstner, Elizabeth; Stufflebeam, Steve; Sorenson, Greg; Harris, Gordon; Freedman, Rachel; Sohl, Jessica; Younger, Jerry; Krop, Ian; Winer, Eric; Lin, Nancy

    2014-01-01

    INTRODUCTION: As systemic therapy improves, brain metastases are increasingly common in patients with breast cancer. Unfortunately, effective therapy with durable control has remained elusive [1]. Combining bevacizumab and cyototoxic chemotherapy is an appealing approach as the anti-angiogenic effect of bevicizumab may improve delivery of cytotoxic drugs to brain tumors. METHODS: We conducted a Phase II study of patients with parenchymal brain metastasis treated with bevacizumab and carboplatin [2]. Patients could have any hormone receptor status or any number of prior therapies. Patients with HER2+ breast cancer also received trastuzamab. Correlative perfusion MRI scans to look at tumor perfusion, blood volume, vessel calibers and relative oxygen saturation (ΔSO2) levels were performed at baseline, day 1, and after 2 months of therapy [3, 4]. For consistency, the largest contrast-enhancing lesion in each patient visible on all three MR visits was selected for analysis. RESULTS: Thirty-eight patients were enrolled in the study of which 32 had, paired evaluable imaging datasets. Compared to baseline, 12/32 patients were identified as responders by a durable increase in ΔSO2 levels at day 1 and at 2 months above a 5% measurement error threshold. The remaining patients were identified by stable (15/32) or reduced (5/32) ΔSO2 levels. Patients responding to therapy showed increased tumor perfusion (Mann-Whitney; P10 µm) were seen across all patients. CONCLUSIONS: Similar to primary brain tumors [2, 3], perfusion MRI demonstrates that anti-angiogenic therapy can induce vascular normalization in a subset of patients with metastatic breast cancer to the brain. Our data indicate that the vascular response may also be associated with improved survival. [1] Lin NU, Lancet Oncol 2013 [2] Sorensen AG, Cancer Res 2012 [3] Emblem KE, Nat Med 2013

  16. Clinical NMR imaging of the brain in children: normal and neurologic disease

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, M.A, (Hammersmith Hospital, London, England); Pennock, J.M.; Bydder, G.M.; Steiner, R.E.; Thomas, D.J.; Hayward, R.; Bryant, D.R.T.; Payne, J.A.; Levene, M.I.; Whitelaw, A.; Dubowitz, L.M.S.; Dubowitz, V.

    1983-11-01

    The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified by virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.

  17. Microglia of the Aged Brain: Primed to be Activated and Resistant to Regulation

    Science.gov (United States)

    Norden, Diana M.; Godbout, Jonathan P.

    2012-01-01

    Innate immunity within the central nervous system (CNS) is primarily provided by resident microglia. Microglia are pivotal in immune surveillance and also facilitate the coordinated responses between the immune system and the brain. For example, microglia interpret and propagate inflammatory signals that are initiated in the periphery. This transient microglial activation helps mount the appropriate physiological and behavioral response following peripheral infection. With normal aging, however, microglia develop a more inflammatory phenotype. For instance, in several models of aging there are increased pro-inflammatory cytokines in the brain and increased expression of inflammatory receptors on microglia. This increased inflammatory status of microglia with aging is referred to as primed, reactive, or sensitized. A modest increase in the inflammatory profile of the CNS and altered microglial function in aging has behavioral and cognitive consequences. Nonetheless, there are major differences in microglial biology between young and old age when the immune system is challenged and microglia are activated. In this context, microglial activation is amplified and prolonged in the aged brain compared to adults. The cause of this amplified microglial activation may be related to impairments in several key regulatory systems with age that make it more difficult to resolve microglial activation. The consequences of impaired regulation and microglial hyper-activation following immune challenge are exaggerated neuroinflammation, sickness behavior, depressive-like behavior and cognitive deficits. Therefore the purpose of this review is to discuss the current understanding of age-associated microglial priming, consequences of priming and reactivity, and the impairments in regulatory systems that may underlie these age-related deficits. PMID:23039106

  18. Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

    Science.gov (United States)

    Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

    2016-11-01

    Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

  19. Functional brain imaging of episodic memory decline in ageing.

    Science.gov (United States)

    Nyberg, L

    2017-01-01

    The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  20. Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction.

    Science.gov (United States)

    Lancaster, Jenessa; Lorenz, Romy; Leech, Rob; Cole, James H

    2018-01-01

    Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalization to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimizing resampling parameters using Bayesian optimization. Using data on N = 2003 healthy individuals (aged 16-90 years) we trained support vector machines to (i) distinguish between young (50 years) brains (classification) and (ii) predict chronological age (regression). We also evaluated generalisability of the age-regression model to an independent dataset (CamCAN, N = 648, aged 18-88 years). Bayesian optimization was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values. When distinguishing between young and old brains a classification accuracy of 88.1% was achieved, (optimal voxel size = 11.5 mm 3 , smoothing kernel = 2.3 mm). For predicting chronological age, a mean absolute error (MAE) of 5.08 years was achieved, (optimal voxel size = 3.73 mm 3 , smoothing kernel = 3.68 mm). This was compared to performance using default values of 1.5 mm 3 and 4mm respectively, resulting in MAE = 5.48 years, though this 7.3% improvement was not statistically significant. When assessing generalisability, best performance was achieved when applying the entire Bayesian optimization framework to

  1. Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction

    Directory of Open Access Journals (Sweden)

    Jenessa Lancaster

    2018-02-01

    Full Text Available Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalization to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimizing resampling parameters using Bayesian optimization. Using data on N = 2003 healthy individuals (aged 16–90 years we trained support vector machines to (i distinguish between young (<22 years and old (>50 years brains (classification and (ii predict chronological age (regression. We also evaluated generalisability of the age-regression model to an independent dataset (CamCAN, N = 648, aged 18–88 years. Bayesian optimization was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values. When distinguishing between young and old brains a classification accuracy of 88.1% was achieved, (optimal voxel size = 11.5 mm3, smoothing kernel = 2.3 mm. For predicting chronological age, a mean absolute error (MAE of 5.08 years was achieved, (optimal voxel size = 3.73 mm3, smoothing kernel = 3.68 mm. This was compared to performance using default values of 1.5 mm3 and 4mm respectively, resulting in MAE = 5.48 years, though this 7.3% improvement was not statistically significant. When assessing generalisability, best performance was achieved when applying the entire Bayesian

  2. Accelerated Aging of Selective Brain Structures in HIV Infection: A Controlled, Longitudinal MRI Study

    Science.gov (United States)

    Pfefferbaum, Adolf; Rogosa, David A.; Rosenbloom, Margaret J.; Chu, Weiwei; Sassoon, Stephanie A.; Kemper, Carol A.; Deresinski, Stanley; Rohlfing, Torsten; Zahr, Natalie M.; Sullivan, Edith V.

    2014-01-01

    Advances in treatment have transformed HIV infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 MRIs and a battery of neuropsychological tests collected two or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; CSF-filled spaces showed increase in volume for both groups. Although HIV infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacological treatment and control of further infection, has the potential of abating decline in associated, higher-order functions, notably, explicit memory, executive

  3. Brain protein synthesis in normal and demented patients. A study by P.E.T. with 11C-L methionine

    International Nuclear Information System (INIS)

    Bustany, P.; Soussaline, F.; Comar, D.; Henry, J.F.

    1982-09-01

    A compartmental model representing protein synthesis in the brain was validated experimentally in 9 baboons. After sequential injections of 11 C, 3 H and 14 C methionines on the same animal, followed by P.E.T. recording of the γ activity in a chosen brain section with time, the distribution of methionine injected into the different compartments of the model after a bolus was measured by crushing and precipitation with T.C.A. The agreement between direct in vitro findings and computed results is excellent. This method of studying brain protein synthesis in vivo was applied to 28 Alzheimer dementia cases and 20 normal subjects of the same age. The correlation between the results of clinical and psychometric tests and the brain protein synthesis activity confirms an anomaly in this biochemical synthesis process during the illness. A 65% fall in activity may be found in the frontal lobes of certain patients

  4. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    Science.gov (United States)

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  5. Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

    DEFF Research Database (Denmark)

    Cramer, Stig Præstekær; Simonsen, Helle Juhl; Frederiksen, Jette Lautrup Battistini

    2013-01-01

    To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.......To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics....

  6. Hierarchical clustering of Alzheimer and "normal" brains using elemental concentrations and glucose metabolism determined by PIXE, INAA and PET

    NARCIS (Netherlands)

    Cutts, DA; Spyrou, NM; Maguire, RP; Leenders, KL

    Brain tissue samples, obtained from the Alzheimer Disease Brain Bank, Institute of Psychiatry, London, were taken from both left and right hemispheres of three regions of the cerebrum, namely the frontal, parietal and occipital lobes for both Alzheimer and 'normal' subjects. Trace element

  7. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  8. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  9. Cognitive decline and brain pathology in aging--need for a dimensional, lifespan and systems vulnerability view.

    Science.gov (United States)

    Walhovd, Kristine B; Fjell, Anders M; Espeseth, Thomas

    2014-06-01

    Changes in brain structure and activity as well as cognitive function are commonly seen in aging. However, it is not known when aging of brain and cognition starts, and how much of the changes observed in seemingly healthy older adults that can be ascribed to incipient neurodegenerative disease. Recent research has yielded evidence that the borders between development and aging sometimes can be fuzzy, as can the borders between dementing disease and normal age changes. In this review, we argue that many factors affecting cognitive decline and dementia represents quantitative rather than qualitative differences in characteristics that commonly exist in the population. Further, factors known to affect brain and cognition in aging will often do so through a life-long accumulation of impact, and does not need to be specific to aging. And finally, a host of environmental and genetic factors and their interplay determine optimal aging, leaving room for potential for environmental interventions to affect the outcome of the aging process. Together, we argue that these factors call for a dimensional rather than categorical, lifespan rather than aging, and multidimensional systems-vulnerability rather than simple "hypothetical biomarker" model of age-associated cognitive decline and dementia. This has implications for how we should view lifespan trajectories of change in brain and cognitive function, and how we can study, prevent, diagnose and treat age-associated cognitive deficits. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  10. NREM sleep oscillations and brain plasticity in aging

    Directory of Open Access Journals (Sweden)

    Stuart eFogel

    2012-12-01

    Full Text Available The human electroencephalogram (EEG during non-rapid eye movement sleep (NREM is characterized mainly by high-amplitude (> 75 µV, slow-frequency (< 4 Hz waves (slow waves; SW and sleep spindles (~11-15 Hz; > 0.25 s. These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.

  11. MRI of spinal bone marrow: part I, techniques and normal age-related appearances.

    Science.gov (United States)

    Shah, Lubdha M; Hanrahan, Christopher J

    2011-12-01

    This article reviews MRI protocols, including routine and nonroutine pulse sequences as well as the normal MRI appearance of spinal marrow and expected age-related changes. Routine MRI of the spine provides useful evaluation of the spinal bone marrow, but nonroutine MRI pulse sequences are increasingly being used to evaluate bone marrow pathology. An understanding of MRI pulse sequences and the normal and age-related appearances of bone marrow is important for the practicing radiologist.

  12. The venous manifestations of pulse wave encephalopathy: windkessel dysfunction in normal aging and senile dementia

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, Grant A. [Locked Bag 1, Newcastle Region Mail Center, Department of Medical Imaging, John Hunter Hospital, Newcastle (Australia); Levi, Christopher R.; Wang, Yang; Lovett, Elizabeth C. [Hunter Medical Research Institute, Clinical Neurosciences Program, Newcastle (Australia); Schofield, Peter [James Fletcher Hospital, Neuropsychiatry Unit, Newcastle (Australia)

    2008-06-15

    Cerebral arterial, venous and cerebrospinal fluid (CSF) pulsations are closely coupled and this produces pulsation dampening or the windkessel effect. Normal pressure hydrocephalus is a manifestation of the breakdown of this windkessel effect with altered CSF and venous pulsations being noted. The aim of this study was to show that dysfunction of the windkessel mechanism is also a component of normal aging and senile dementia. The study group comprised 24 patients classified as either early senile dementia of Alzheimer's type (SDAT) or vascular dementia (VaD). The patients with dementia were compared with 12 age-matched non-cognitively impaired subjects, and 12 normal young individuals were compared with the normal aging group. MRI flow quantification was used to measure the nonpulsatile and pulsatile components of blood flow as well as the pulsation at the tentorial incisura. With normal aging blood flow decreased but arterial pulsations increased in volume by 49% (P = 0.003). The CSF vented via the tentorial incisura does not change significantly with age and therefore increased venous pulsation is necessary. In patients with VaD the arterial pulse volume was higher by 24% and the straight sinus pulsation was higher by 57% than in normal aging subjects (P = 0.05 and P = 0.03, respectively). In patients with SDAT the total venous pulsation volumes were similar to those in normal aging subjects but there was less basal sinus pulsation. Normal aging, SDAT and VaD are associated with alterations in venous pulsation due to a breakdown of the windkessel effect. (orig.)

  13. Effects of active music therapy on the normal brain: fMRI based evidence.

    Science.gov (United States)

    Raglio, Alfredo; Galandra, Caterina; Sibilla, Luisella; Esposito, Fabrizio; Gaeta, Francesca; Di Salle, Francesco; Moro, Luca; Carne, Irene; Bastianello, Stefano; Baldi, Maurizia; Imbriani, Marcello

    2016-03-01

    The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings.

  14. No late effect of ionizing radiation on the aging-related oxidative changes in the mouse brain

    International Nuclear Information System (INIS)

    Jang, Beom Su; Kim, Seol Wha; Jung, U Hee; Jo, Sung Kee

    2010-01-01

    Radiation-induced late injury to normal tissue is a primary area of radiation biology research. The present study was undertaken to investigate whether the late effect of the ionizing radiation appears as an age-related oxidative status in the brain. Three groups of 4-month old C57BL/6 mice that were exposed to 137 Cs γ-rays at a single dose (5 Gy) or fractionated doses (1 Gy x 5 times, or 0,2 Gy x 25 times) at 2 months old were investigated for the oxidative status of their brains with both young (2-month) and old (24-month) mice. A significant (p< o.05) decrease in superoxide dismutase (SOD) activity was observed in old mice brains compared with that of the young mice. Malondialdehyde (MDA) content was significantly (p<0.05) increased in the old mice brain. However, any significant difference in SOD activity and MDA contents of the irradiated brain was not observed compared to age-matched control group mice. SOD activity and MDA content were observed within good parameters of brain aging and there no late effects on the age-related oxidative level in the γ-ray irradiated mice brains

  15. Neural Plastic Effects of Cognitive Training on Aging Brain.

    Science.gov (United States)

    Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  16. Neural Plastic Effects of Cognitive Training on Aging Brain

    Directory of Open Access Journals (Sweden)

    Natalie T. Y. Leung

    2015-01-01

    Full Text Available Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n=109 and the Active Control Group (n=100. Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  17. The effects of normal aging on multiple aspects of financial decision-making.

    Directory of Open Access Journals (Sweden)

    Dorien F Bangma

    Full Text Available Financial decision-making (FDM is crucial for independent living. Due to cognitive decline that accompanies normal aging, older adults might have difficulties in some aspects of FDM. However, an improved knowledge, personal experience and affective decision-making, which are also related to normal aging, may lead to a stable or even improved age-related performance in some other aspects of FDM. Therefore, the present explorative study examines the effects of normal aging on multiple aspects of FDM.One-hundred and eighty participants (range 18-87 years were assessed with eight FDM tests and several standard neuropsychological tests. Age effects were evaluated using hierarchical multiple regression analyses. The validity of the prediction models was examined by internal validation (i.e. bootstrap resampling procedure as well as external validation on another, independent, sample of participants (n = 124. Multiple regression and correlation analyses were applied to investigate the mediation effect of standard measures of cognition on the observed effects of age on FDM.On a relatively basic level of FDM (e.g., paying bills or using FDM styles no significant effects of aging were found. However more complex FDM, such as making decisions in accordance with specific rules, becomes more difficult with advancing age. Furthermore, an older age was found to be related to a decreased sensitivity for impulsive buying. These results were confirmed by the internal and external validation analyses. Mediation effects of numeracy and planning were found to explain parts of the association between one aspect of FDM (i.e. Competence in decision rules and age; however, these cognitive domains were not able to completely explain the relation between age and FDM.Normal aging has a negative influence on a complex aspect of FDM, however, other aspects appear to be unaffected by normal aging or improve.

  18. MRI Volumetry of Hippocampus and Amygdala in Normal Aging, Mild Cognitive Impairment and Alzheimer's Disease Subjects

    International Nuclear Information System (INIS)

    Suphaphong, S.; Tritanon, O.; Laothamatas, J.; Sungkarat, W.

    2012-01-01

    The Alzheimer's disease (AD) and mild cognitive impairment (MCI) can affect memory and daily living. Non- invasive diagnostic tools such as MRI can be useful to discriminate the patients from normal group.This study aims to compare the relative volumes of hippocampus and amygdala, to suggest the relative normal volumes, and to evaluate MRI automatic volumetry as a diagnostic tool. The MRI images of 130 subjects were retrospectively studied (Turbo field echo (TFE), acquired with a 3-Tesla Philips scanner). The image data were processed with Free Surfer (automatic segmentation and volumetry). The resultant volumes were corrected for brain size differences with intracranial volumes (ICV), and then analysed with SPSS (v. 17.0). There are differences of hippocampus and amygdala relative volumes between normal, MCI, and AD subjects at p < 0.001. The volume reductions of hippocampus in MCI and AD groups compared to normal group are about 8 % and 28 %, while those of amygdala are about 10 % and 34 %, respectively. The relative volumes of hippocampus (compared to ICV) in normal aging are 0.002617 ± 0.000278 (right) and 0.002553 ± 0.000257 (left), while those of amygdala are 0.001231 ± 0.000165 (right) and 0.001096 ± 0.000144 (left). There are no differences of relative volumes affected by gender in normal, MCI, and AD. There is a highly significant difference of relative volume affected by brain side in normal group (p < 0.001) but not in MCI (p = 0.119 and 0.077) and AD (p = 0.713 and 0.250), for hippocampus and amygdala, respectively. These results demonstrate that there are volume losses of hippocampus and amygdala in both diseases. Automatically measured hippocampus and amygdala volumes can be used as a measure indicating MCI and AD. The abnormal disturbance of volume affected by brain side may indicate the progression of both diseases. The hippocampus and amygdala volumes can be used as one of diagnostic tools to confirm the diagnosis of MCI or AD. The volume

  19. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    Directory of Open Access Journals (Sweden)

    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  20. Motor control and aging: links to age-related brain structural, functional, and biochemical effects.

    Science.gov (United States)

    Seidler, Rachael D; Bernard, Jessica A; Burutolu, Taritonye B; Fling, Brett W; Gordon, Mark T; Gwin, Joseph T; Kwak, Youngbin; Lipps, David B

    2010-04-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems-primarily the dopaminergic system-may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of "supply and demand". Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. Copyright 2009 Elsevier Ltd. All rights reserved.

  1. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  2. Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging.

    Science.gov (United States)

    Marks, Shawn M; Lockhart, Samuel N; Baker, Suzanne L; Jagust, William J

    2017-03-22

    Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment. SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy. Copyright © 2017 the authors 0270-6474/17/373192-10$15.00/0.

  3. The effects of age on dopamine receptors measured by positron tomography in the living human brain

    International Nuclear Information System (INIS)

    Wong, D.F.; Wagner, E.N. Jr.; Dannals, R.F.

    1984-01-01

    C-11 n-methylspiperone has been used to measure dopamine (D2) receptors in the caudate and putamen of 30 normal persons. In vitro studies in rodent brain revealed a high affinity for dopamine (D2) receptors and five fold less for serotonin (S2) receptors. In vivo drug competition studies in rodents demonstrated that 90% of striatal binding is to dopamine receptors. In the frontal cortex, the majority of receptor binding is to serotonin receptors. Thirty normal volunteers aged 19 to 73 years were screened for normality by medical, neurological and neuropsychological examinations. Positron tomography was performed serially for 2 hours after injection. In 10 subjects there was good agreement between activity in arterial samples and that in venous samples from a heated hand. Binding in the dopamine rich caudate and putamen progressively increased while binding in the dopamine poor cerebellum decreased. The dopamine receptor density was estimated by the ratio of the caudate-to-cerebellar mean counts/pixel (Ca/Cb) and putamen-to-cerebellar mean counts/pixel (Pu/Cb). The ratios (Ca/Cb, Pu/Cb) increased linearly with time (r>0.95) for each subject. There was a decrease (Ca/Cb) with age (0.8%/yr) that could be approximated with a linear fit: (Ca/Cb = -.02 age + 3.92, r=.6). For the 21 males alone, the decrease was (1.1%/yr, r=.7 , p <.01), while for the 9 females there was no significant decrease with age. Similar findings were noted in the putamen. This decline in dopamine receptor density with age has been reported in rodent and human autopsy studies, but never before in the living human brain

  4. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    stress, excitotoxicity, amyloid-β toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening...... in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  5. The Impact of Glial Activation in the Aging Brain

    Science.gov (United States)

    Lynch, Aileen M.; Murphy, Kevin J.; Deighan, Brian F.; O'Reilly, Julie-Ann.; Gun'ko, Yuri K.; Cowley, Thelma R.; Gonzalez-Reyes, Rodrigo E.; Lynch, Marina A.

    2010-01-01

    The past decade or so has witnessed a rekindling of interest in glia requiring a re-evaluation of the early descriptions of astrocytes as merely support cells, and microglia as adopting either a resting state or an activated state in a binary fashion. We now know that both cell types contribute to the optimal functioning of neurons in the healthy brain, and that altered function of either cell impacts on neuronal function and consequently cognitive function. The evidence indicates that both astrocytic and microglial phenotype change with age and that the shift from the resting state is associated with deterioration in synaptic function. In this review, we consider the rapidly-expanding array of functions attributed to these cells and focus on evaluating the changes in cell activation that accompany ageing. PMID:22396865

  6. Dietary fish oil modestly attenuates the effect of age on diastolic function but has no effect on memory or brain inflammation in aged rats.

    Science.gov (United States)

    Sergeant, Susan; McQuail, Joseph A; Riddle, David R; Chilton, Floyd H; Ortmeier, Steven B; Jessup, Jewell A; Groban, Leanne; Nicolle, Michelle M

    2011-05-01

    Fish oil (FO) mediates a number of cardioprotective benefits in patients with cardiovascular disease. In the absence of cardiovascular disease, however, the effects of FO on cardiac structure and function are not clear. In addition, it is not known if an effective dosing strategy for attenuating age-related cardiac dysfunction is also effective at limiting cognitive dysfunction. Therefore, we determined if 4 months of FO supplementation in aged rats would lessen age-related cardiac dysfunction while concomitantly preventing the cognitive decline that is normally observed in this population. The results indicate that FO initiated late in life modifies diastolic function in a small but positive way by attenuating the age-related increases in filling pressure, posterior wall thickness, and interstitial collagen without mitigating age-related deficits in memory or increases in brain inflammation. These data raise the possibility that FO supplementation for purposes of cardiac and brain protection may need to occur earlier in the life span.

  7. [Artificial intelligence meeting neuropsychology. Semantic memory in normal and pathological aging].

    Science.gov (United States)

    Aimé, Xavier; Charlet, Jean; Maillet, Didier; Belin, Catherine

    2015-03-01

    Artificial intelligence (IA) is the subject of much research, but also many fantasies. It aims to reproduce human intelligence in its learning capacity, knowledge storage and computation. In 2014, the Defense Advanced Research Projects Agency (DARPA) started the restoring active memory (RAM) program that attempt to develop implantable technology to bridge gaps in the injured brain and restore normal memory function to people with memory loss caused by injury or disease. In another IA's field, computational ontologies (a formal and shared conceptualization) try to model knowledge in order to represent a structured and unambiguous meaning of the concepts of a target domain. The aim of these structures is to ensure a consensual understanding of their meaning and a univariant use (the same concept is used by all to categorize the same individuals). The first representations of knowledge in the AI's domain are largely based on model tests of semantic memory. This one, as a component of long-term memory is the memory of words, ideas, concepts. It is the only declarative memory system that resists so remarkably to the effects of age. In contrast, non-specific cognitive changes may decrease the performance of elderly in various events and instead report difficulties of access to semantic representations that affect the semantics stock itself. Some dementias, like semantic dementia and Alzheimer's disease, are linked to alteration of semantic memory. We propose in this paper, using the computational ontologies model, a formal and relatively thin modeling, in the service of neuropsychology: 1) for the practitioner with decision support systems, 2) for the patient as cognitive prosthesis outsourced, and 3) for the researcher to study semantic memory.

  8. Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

    Science.gov (United States)

    Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

    2016-10-01

    Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

  9. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  10. Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Aadhavi eSridharan

    2012-11-01

    Full Text Available The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction, the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter volume, and fractional anisotropy and mean diffusivity, respectively. We tested the extent to which brain health indexed by gray matter volume, fractional anisotropy, and mean diffusivity were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor times would be correlated with higher volume, higher fractional anisotropy, and lower mean diffusivity in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower gray matter volume in frontal and parietal cortices, and lower fractional anisotropy in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased fractional anisotropy in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in calorie restricted animals compared to controls, indicating a potential protective effect of the dietary

  11. Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

    Science.gov (United States)

    Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

    2016-11-01

    In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m - 2 ) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m - 2 ), both before and 30 min after consumption of a standardized meal (~260 kcal). Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (Pincreased after food intake (Pobese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

  12. Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Okko T Pyykkö

    Full Text Available BACKGROUND: The significance of amyloid precursor protein (APP and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH and Alzheimer's disease (AD is unknown. OBJECTIVE: To investigate the role of soluble APP (sAPP and amyloid beta (Aβ isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF in relation to brain biopsy Aβ and hyperphosphorylated tau (HPτ findings. METHODS: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders, 26 AD (10 mixed iNPH+AD, and 23 others. Biopsy samples were immunostained against Aβ and HPτ. CSF levels of AD-related biomarkers (Aβ42, p-tau, total tau, non-AD-related Aβ isoforms (Aβ38, Aβ40, sAPP isoforms (sAPPα, sAPPβ, proinflammatory cytokines (several interleukins (IL, interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha and biomarkers of neuronal damage (neurofilament light and myelin basic protein were measured. All patients were genotyped for APOE. RESULTS: Lumbar CSF levels of sAPPα were lower (p<0.05 in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPβ showed a similar trend (p = 0.06. CSF sAPP isoform levels showed no association to Aβ or HPτ in the brain biopsy. Quantified Aβ load in the brain biopsy showed a negative correlation with CSF levels of Aβ42 in ventricular (r = -0.295, p = 0.003 and lumbar (r = -0.356, p = 0.01 samples, while the levels of Aβ38 and Aβ40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001 were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure

  13. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  14. Analysis of the brain proton magnetic resonance spectroscopy - differences between normal grey and white matter

    International Nuclear Information System (INIS)

    Krukowski, P.; Podgorski, P.; Guzinski, M.; Szewczyk, P.; Sasiadek, M.

    2010-01-01

    Background: The proton magnetic resonance spectroscopy (HMRS) is a non-invasive diagnostic method that allows for an assessment of the metabolite concentration in tissues. The sources of the strongest resonance signals within the brain are N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol (mI) and water. The aim of our study was to analyse the ratios of metabolite signals within the brain in HMRS in the healthy population, to define the differences between the grey and white matter spectra. Material/Methods: We studied prospectively 90 subjects aged from 8 to 80 years (mean 43.3 years, SD=17.9), without neurological symptoms or abnormalities in magnetic resonance imaging. In all patients, brain HMRS with Signa HDx 1.5 T MR unit (GE Healthcare) was performed with PRESS sequence, using a single voxel method, at TE of 35 ms and TR of 1500 ms. Spectroscopic evaluation involved voxels placed in the white matter of parietal lobe (PWM) and the grey matter of posterior cingulate gyrus (PGM). On the basis of the intensity of NAA, Cr, Cho, mI and water signals, the proportions of these signals were calculated, as well as the ratio of the analyzed metabolite signal to the sum of signals of NAA, Cho, Cr and mI (%Met) in the PGM and PWM voxels. We compared the proportions in the same patients in PGM and PWM voxels. Results: There has been a statistically significant difference between the proportions of a majority of the metabolite ratios evaluated in PGM and PWM, indicating the higher concentration of NAA, Cr and mI in grey matter, and higher concentration of Cho in white matter. Conclusions: HMRS spectra of the brain grey and white matter differ significantly. The concentrations of NAA, Cr and mI are higher in grey matter, while of choline - in the white matter. (authors)

  15. Genetic Determinants of Cognitive Function and Age-Related Brain Changes

    NARCIS (Netherlands)

    M. Schuur (Maaike)

    2010-01-01

    textabstractThe brain is by far the most complicated structure of the human being, and its malfunction is characterized by various degrees and types of morbidity. Several brain functions deteriorate with increasing age during life. Cognitive decline and age-related brain pathology are common in

  16. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  17. Selection of Candidate Housekeeping Genes for Normalization in Human Postmortem Brain Samples

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    Aldo Pagano

    2011-08-01

    Full Text Available The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer’s disease (AD suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples.

  18. MRI and brain spect findings in patients with unilateral temporal lobe epilepsy and normal CT scan

    Directory of Open Access Journals (Sweden)

    P.G. Carrilho

    1994-06-01

    Full Text Available 26 patients with temporal lobe epilepsy clinically documented by several abnormal interictal surface EEGs with typical unitemporal epileptiform activity and a normal CT scan were studied. Interictal99mTC HMPAO brain SPECT and MRI were performed in all subjects. Abnormalities were shown in 61.5% of MRI (n=16 and 65.4% of SPECT (n=17. Hippocampal atrophy associated to a high signal on T2-weighted MRI slices suggesting mesial temporal sclerosis was the main finding (n=12; 75% of abnormal MRI. MRI correlated well to surface EEG in 50% (n=13. There was also a good correlation between MRI and SPECT in 30.7% (n=8. SPECT and EEG were in agreement in 57.7% (n=l5. MRI, SPECT and EEG were congruent in 26.9% (n=7. These results support the usefulness of interictal brain SPECT and MRI in detecting lateralized abnormalities in temporal lobe epilepsy. On the other hand, in two cases, interictal SPECT correlated poorly with surface EEG. This functional method should not be used isolately in the detection of temporal lobe foci. MRI is more useful than CT as a neuroimaging technique in temporal lobe epilepsy. It may detect small structural lesions and mesial temporal lobe sclerosis which are not easily seen with traditional CT scanning.

  19. The neuro-radiological anatomy of the normal and abnormal rat brain

    International Nuclear Information System (INIS)

    Schumacher, M.; Doller, P.; Voigt, K.

    1979-01-01

    In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment. (orig.) [de

  20. Normal myelination of the child brain on MRI - a meta-analysis; Die normale Myelinisierung des kindlichen Gehirns in der MRT - eine Metaanalyse

    Energy Technology Data Exchange (ETDEWEB)

    Staudt, M.; Grodd, W. [Tuebingen Univ. (Germany). Abt. fuer Neuroradiologie; Kraegeloh-Mann, I. [Tuebingen Univ. (Germany). Abt. Entwicklungsneurologie und Neuropaediatrie

    2000-10-01

    Purpose: To establish age limits for the assessment of normal myelination of the brain on T{sub 1}-weighted (T{sub 1}w) and T{sub 2}-weighted (T{sub 2}w) images. Method: Comparison of previous publications (Barkovich et al. 1988, Grodd 1993, Hayakawa et al. 1990, Hittmair et al. 1994, Martin et al. 1988/1990/1991, Nakagawa et al. 1998, Staudt et al. 1993/1994, Stricker et al. 1990). Results: Despite technical and methodological differences, these studies principally agreed on the timing of myelination for most regions of the brain. Thus, a common timetable could be established: At 1 month, myelin is visible on both T{sub 1}w and T{sub 2}w in the medulla oblongata, tegmentum pontis, cerebellar peduncles and vermis, quadrigeminal plate, decussation of superior cerebellar peduncles, thalamus, posterior limb of internal capsule, optic radiation, corona radiata. Thereafter, the myelin-typical signal in the different regions of the brain should be present at the following ages (M=months): Anterior limb of internal capsule (2 M: T{sub 1}w; 7 M: T{sub 2}w), splenium of corpus callosum (4 M: T{sub 1}w; 6 M: T{sub 2}w), genu of corpus callosum (6 M: T{sub 1}w; 8 M: T{sub 2}w), centrum semiovale (2 M: T{sub 1}w; 7 M: T{sub 2}w). Branching of myelin into the gyri of the telencephalon (=arborization) appears at the latest at: occipital lobe (5 M: T{sub 1}w; 12 M: T{sub 2}w) and frontal lobe (7 M: T{sub 1}w; 14 M: T{sub 2}w). Conclusion: These extracted age limits can be used for a more reliable assessment of myelination than the time-tables from a single study. (orig.) [German] Ziel: Ermittlung von Altersgrenzen fuer die MR-tomographisch erfassbare Myelinisierung des kindlichen Gehirns in T{sub 1}- und T{sub 2}-gewichteten Aufnahmen (T{sub 1}w, T{sub 2}w). Methode: Vergleich bisher publizierter Zeitangaben (Barkovich et al 1988, Grodd 1993, Hayakawa et al 1990, Hittmair et al 1994, Martin et al 1988/1990/1991, Nakagawa et al 1998, Staudt et al 1993/1994, Stricker et al 1990

  1. Age-related contrast enhancement study of normal bone marrow in lumbar spinal MR imaging

    International Nuclear Information System (INIS)

    Kim, Young A; Ha, Doo Hoe

    1999-01-01

    The purpose of this study was to evaluate the degree of contrast enhancement of normal bone marrow in L-spine relating to aging and to determine the range of contrast enhancement in normal bone marrow. We analyzed a total of 120 patients (20 per decade) who had undergone lumbar spinal MRI and who ranged in age from the 2nd decade to more than the 7th. Bone marrow revealed no abnormal pathology. Sagittal T1-weighted spin echo sequences were obtained before and after gadolinium administration. For each sequence, a region of interest was drawn within the L1 vertebral body from the midsagittal slice. Signal intensity (SI) values of each sequence were ascertained and the percentage increase in SI was calculated. After contrast enhancement, lumbar MRI revealed no statistically significant in the percentage increase in SI of normal bone marrow in relation to aging. Most patients (99%) however showed an SI increase of between 10% and 49%. In only four, none of whom were aged over 40, was this increase above 50%. Lumbar MRI, revealed no statistically significant difference in percentage increase in SI in normal bone marrow relating to aging, but when the increase is above 50% in a patient aged over 40, bone marrow pathology should be further investigated

  2. Localizing Age-Related Changes in Brain Structure Using Voxel-Based Morphometry

    Directory of Open Access Journals (Sweden)

    Shu Hua Mu

    2017-01-01

    Full Text Available Aim. We report the dynamic anatomical sequence of human cortical gray matter development from late childhood to young adults using VBM and ROI-based methods. Method. The structural MRI of 91 normal individuals ranging in age from 6 to 26 years was obtained and the GMV for each region was measured. Results. Our results showed that the earliest loss of GMV occurred in left olfactory, right precuneus, caudate, left putamen, pallidum, and left middle temporal gyrus. In addition, the trajectory of maturational and aging showed a linear decline in GMV on both cortical lobes and subcortical regions. The most loss of gray matter was observed in the parietal lobe and basal ganglia, whereas the less loss occurred in the temporal lobe and hippocampus, especially in the left middle temporal pole, which showed no decline until 26 years old. Moreover, the volumes of GM, WM, and CSF were also assessed for linear age effects, showing a significant linear decline in GM with age and a significant linear increase in both WM and CSF with age. Interpretation. Overall, our findings lend support to previous findings of the normal brain development of regional cortex, and they may help in understanding of neurodevelopmental disorders.

  3. Evaluation of the Normal Fetal Kidney Length and Its Correlation with Gestational Age

    OpenAIRE

    Farrokh Seilanian Toosi; Hossein Rezaie-Delui

    2013-01-01

    A true estimation of gestational age (GA) plays an important role in quality maternity care and scheduling the labor date. This study aimed to evaluate the normal fetal kidney length (KL) and its correlation with GA. A cross-sectional study on 92 pregnant women between 8th and 10th week of gestation with normal singleton pregnancy underwent standard ultrasound fetal biometry and kidney length measurement. univariate and multivariate linear regression analysis was used to create a predictive e...

  4. Prediction of endometriosis by transvaginal ultrasound in reproductive-age women with normal ovarian size

    OpenAIRE

    Tamer H. Said; Amal Z. Azzam

    2014-01-01

    Objective: To predict endometriosis by transvaginal ultrasound (TVS) in reproductive-age women with normal ovarian size. Design: Prospective study. Setting: El-Shatby Maternity Hospital, Alexandria University. Patients: 125 Women with symptoms suggestive of endometriosis and with normal ovarian size during TVS. Interventions: Patients were subjected to high frequency ultrasound and evaluated for the presence of ultrasound signs of endometriosis (TVS-based soft markers). All patien...

  5. Normal aging does not impair orbitofrontal-dependent reinforcer devaluation effects

    Directory of Open Access Journals (Sweden)

    Teghpal eSingh

    2011-03-01

    Full Text Available Normal aging is associated with deficits in cognitive flexibility thought to depend on prefrontal regions such as the orbitofrontal cortex. Here, we used Pavlovian reinforcer devaluation to test whether normal aging might also affect the ability to use outcome expectancies to guide appropriate behavioral responding, which is also known to depend on the orbitofrontal cortex. Both young and aged rats were trained to associate a 10 second conditioned stimulus (CS+ with delivery of a sucrose pellet. After training, half of the rats in each age group received the sucrose pellets paired with illness induced by LiCl injections; the remaining rats received sucrose and illness explicitly unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe test. Although aged rats displayed lower responding levels overall, both young and aged rats conditioned to the CS+ and developed a conditioned taste aversion following reinforcer devaluation. Furthermore, during the extinction probe test, both young and aged rats spontaneously attenuated conditioned responding to the cue as a result of reinforcer devaluation. These data show that normal aging does not affect the ability to use expected outcome value to appropriately guide Pavlovian responding. This result indicates that deficits in cognitive flexibility are dissociable from other known functions of prefrontal - and particularly orbitofrontal - cortex. 

  6. Age and Dyssynergia Subtypes Associated With Normal Sphincter Pressures in Women With Fecal Incontinence.

    Science.gov (United States)

    James-Stevenson, Toyia; Xu, Huiping; Heit, Michael; Shin, Andrea

    2017-06-27

    Fecal incontinence (FI) is frequently associated with low sphincter pressures, sensory abnormalities, and advanced age. Twenty-three percent of patients with FI and 22% of healthy patients demonstrate dyssynergic defecation (DD) on high-resolution anorectal manometry. Overflow incontinence occurs in some DD patients with normal resting and squeeze anal sphincter pressures. Our aim was to identify factors associated with normal sphincter pressures in women with FI. We reviewed medical records of 134 women with FI. Patients with normal resting and squeeze anal pressures were compared with those with abnormal pressures using Wilcoxon rank sum test and Fisher exact. Multivariable logistic regression was performed to identify factors associated with normal resting and squeeze anal pressures. Among 134 women, abnormal resting and/or squeeze pressures were identified in 113 and normal pressures were identified in 21. Women with normal sphincter pressures were younger (mean age 52.7 ± 10.8 years vs 59.0 ± 14.0 years, P = 0.036), more often had abnormal defecation indices (100% vs 83.2%, P = 0.043) and higher rectal defecation pressures (30.8 ± 18.8 mm Hg vs 50.8 ± 22.6 mm Hg, P normal and abnormal sphincter pressure groups (P = 0.021). Dyssynergia subtypes I or III (odds ratio, 7.2; 95% confidence interval, 1.8-28.8) and age younger than 67 years (odds ratio, 8.5; 95% confidence interval, 1.5-48.6) were associated with greater odds of having normal sphincter pressures. Female FI patients with normal anal sphincter pressures are younger, have higher rectal defecation pressures, and more often have type I or type III DD.

  7. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging.

    Science.gov (United States)

    Singh, Ram Harsh; Narsimhamurthy, K; Singh, Girish

    2008-12-01

    Ayurveda is the oldest system of Medicine in the world, its antiquity going back to the Vedas. It adapts a unique holistic approach to the entire science of life, health and cure. The areas of special consideration in Ayurveda are geriatrics, rejuvenation, nutrition, immunology, genetics and higher consciousness. The Ayurvedic texts describe a set of rejuvenative measures to impart biological sustenance to the bodily tissues. These remedies are called Rasayana which are claimed to act as micronutrients. Some of these Rasayanas are organ and tissue specific. Those specific to brain tissue are called Medhya Rasayana. Such Rasayanas retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and memory enhancing effect. In addition to the long tradition of textual and experience-based evidence for their efficacy, certain recent studies conducted on these traditional remedies on scientific parameters have shown promising results which have been reviewed in this paper for providing lead for further studies. The popular Medhya Rasayanas are Ashwagandha (Withania somnifera Dunal), Brahmi (Bacopa monnieri Linn), Mandukaparni (Centella asiatica Linn) and Sankhapuspi (Convolvulus pluricaulis Chois).

  8. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    Science.gov (United States)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  9. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.

    Science.gov (United States)

    García-Mesa, Yoelvis; Colie, Sandra; Corpas, Rubén; Cristòfol, Rosa; Comellas, Francesc; Nebreda, Angel R; Giménez-Llort, Lydia; Sanfeliu, Coral

    2016-01-01

    Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Brain white matter damage in aging and cognitive ability in youth and older age.

    Science.gov (United States)

    Valdés Hernández, Maria Del C; Booth, Tom; Murray, Catherine; Gow, Alan J; Penke, Lars; Morris, Zoe; Maniega, Susana Muñoz; Royle, Natalie A; Aribisala, Benjamin S; Bastin, Mark E; Starr, John M; Deary, Ian J; Wardlaw, Joanna M

    2013-12-01

    Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = -0.14, p age 11 IQ (β = -0.08, p age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  11. mTOR signaling and its roles in normal and abnormal brain development.

    Directory of Open Access Journals (Sweden)

    Nobuyuki eTakei

    2014-04-01

    Full Text Available Target of rapamycin (TOR was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mTOR (mammalian TOR. mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system (CNS, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

  12. Easy and reliable radioimmunoassay of serum androstenedione: age-related normal values in 252 females aged 2 to 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hummer, L.; Nielsen, M.D.; Christiansen, C. (Glostrup Hospital (Denmark))

    1983-06-01

    A simple, non-chromatographic radioimmunoassay for the measurement of androstenedione (A-dione) in serum and based on a commercially available antiserum is described. The antibody-bound fraction was separated from the free fraction by a gel-centrifugation procedure. The method was used to establish reference values for normal females, based on determination in 252 normal females from 2 to 70 years of age. The data support the statement that the decline with age after puberty in the overall production of A-dione is mainly caused by a reduction in the adreno-derived A-dione, since the mean concentration of A-dione in age-matched pre- and postmenopausal women was very similar.

  13. Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD.

    Science.gov (United States)

    Fotenos, A F; Snyder, A Z; Girton, L E; Morris, J C; Buckner, R L

    2005-03-22

    To test the hypotheses 1) that whole-brain volume decline begins in early adulthood, 2) that cross-sectional and longitudinal atrophy estimates agree in older, nondemented individuals, and 3) that longitudinal atrophy accelerates in the earliest stages of Alzheimer disease (AD). High-resolution, high-contrast structural MRIs were obtained from 370 adults (age 18 to 97). Participants over 65 (n = 192) were characterized using the Clinical Dementia Rating (CDR) as either nondemented (CDR 0, n = 94) or with very mild to mild dementia of the Alzheimer type (DAT, CDR 0.5 and 1, n = 98). Of these older participants, 79 belonged to a longitudinal cohort and were imaged again a mean 1.8 years after baseline. Estimates of gray matter (nGM), white matter (nWM), and whole-brain volume (nWBV) normalized for head sizes were generated based on atlas registration and image segmentation. Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss. Whole-brain volume differences were detected by age 30. The cross-sectional atrophy model overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In those individuals with very mild DAT, atrophy rate more than doubled (-0.98% per year). Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.

  14. Microglial Dysfunction in Brain Aging and Alzheimer’s Disease

    Science.gov (United States)

    Mosher, Kira Irving; Wyss-Coray, Tony

    2014-01-01

    Microglia, the immune cells of the central nervous system, have long been a subject of study in the Alzheimer’s disease (AD) field due to their dramatic responses to the pathophysiology of the disease. With several large-scale genetic studies in the past year implicating microglial molecules in AD, the potential significance of these cells has become more prominent than ever before. As a disease that is tightly linked to aging, it is perhaps not entirely surprising that microglia of the AD brain share some phenotypes with aging microglia. Yet the relative impacts of both conditions on microglia are less frequently considered in concert. Furthermore, microglial “activation” and “neuroinflammation” are commonly analyzed in studies of neurodegeneration but are somewhat ill-defined concepts that in fact encompass multiple cellular processes. In this review, we have enumerated six distinct functions of microglia and discuss the specific effects of both aging and AD. By calling attention to the commonalities of these two states, we hope to inspire new approaches for dissecting microglial mechanisms. PMID:24445162

  15. Study of regional stability of 99Tcm-ECD distribution in normal brain by SPM and ROI

    International Nuclear Information System (INIS)

    Li Peiyong; Guo Wanhua; Chen Gang; Zhu Chengmo

    2001-01-01

    Objective: To quantify regional cerebral blood flow (rCBF) with repeated 99 Tc m -ECD brain SPECT. Methods: Each of thirteen normal volunteers (31.2 +- 11.8 years old) underwent 12 times of SPECT scanning 1 hour after injection of 99 Tc m -ECD, the acquisition lasted 60 minutes. The distribution of 99 Tc m -ECD in brain was analyzed by SPM and ROI method. Results: There was no difference of regional ECD distribution within 60 min in cortex, basal ganglia and thalamus showed by SPM. ROI analysis showed a very slow change of regional gray matter/white matter (G/W) over time, and the slope of the curve was almost zero. Conclusion: Regional ECD distribution is stable in normal brain. ECD clearance from brain is slow and the changes of it within 60 minutes were of no significant difference

  16. A computed tomography-based spatial normalization for the analysis of [18F] fluorodeoxyglucose positron emission tomography of the brain.

    Science.gov (United States)

    Cho, Hanna; Kim, Jin Su; Choi, Jae Yong; Ryu, Young Hoon; Lyoo, Chul Hyoung

    2014-01-01

    We developed a new computed tomography (CT)-based spatial normalization method and CT template to demonstrate its usefulness in spatial normalization of positron emission tomography (PET) images with [(18)F] fluorodeoxyglucose (FDG) PET studies in healthy controls. Seventy healthy controls underwent brain CT scan (120 KeV, 180 mAs, and 3 mm of thickness) and [(18)F] FDG PET scans using a PET/CT scanner. T1-weighted magnetic resonance (MR) images were acquired for all subjects. By averaging skull-stripped and spatially-normalized MR and CT images, we created skull-stripped MR and CT templates for spatial normalization. The skull-stripped MR and CT images were spatially normalized to each structural template. PET images were spatially normalized by applying spatial transformation parameters to normalize skull-stripped MR and CT images. A conventional perfusion PET template was used for PET-based spatial normalization. Regional standardized uptake values (SUV) measured by overlaying the template volume of interest (VOI) were compared to those measured with FreeSurfer-generated VOI (FSVOI). All three spatial normalization methods underestimated regional SUV values by 0.3-20% compared to those measured with FSVOI. The CT-based method showed slightly greater underestimation bias. Regional SUV values derived from all three spatial normalization methods were correlated significantly (p brain regions or highly variable within study population.

  17. [Idiopathic normal pressure hydrocephalus: High incidence in people over 80 years of age].

    Science.gov (United States)

    Aragonès, Josep Maria; Altimiras, Jacint; Alonso, Francisco; Roura, Pere; Alfonso, Sebastián; Bajo, Lorena

    Idiopathic normal pressure hydrocephalus is usually observed in adults over 60 years of age. The highest incidence of cases is between 70 and 80 years-old, and it could be under-diagnosed in over 80 year-olds. A description is presented on the overall incidence and age group incidence, the delay in the diagnosis, and main outcomes. A descriptive study was performed on patients with idiopathic normal pressure hydrocephalus, in the population of Osona County during the years 2010-2015. The annual incidence rate was 4.43 per 100,000 inhabitants. The incidence increased with age; from 8.09 per 100,000 in the 60 to 69 years age group, to 23.61 per 100,000 in the 70-79 years age group of, and to 37.02 per 100,000 in the 80-89 years age. The delay in the diagnosis was 15.01 ± 10.35 months. All the patients improved after surgery, but only 73.3% of the patients maintained the improvement after one year. Idiopathic normal pressure hydrocephalus is an age related disease and probably underdiagnosed in the elderly. An early diagnosis and a clinical suspicion are essential in patients over 80 years old. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Visual field function in school-aged children with spastic unilateral cerebral palsy related to different patterns of brain damage.

    Science.gov (United States)

    Jacobson, Lena; Rydberg, Agneta; Eliasson, Ann-Christin; Kits, Annika; Flodmark, Olof

    2010-08-01

    To relate visual field function to brain morphology in children with unilateral cerebral palsy (CP). Visual field function was assessed using the confrontation technique and Goldmann perimetry in 29 children (15 males, 14 females; age range 7-17y, median age 11y) with unilateral CP classified at Gross Motor Function Classification System (GMFCS) level I and Manual Ability Classification System levels I to III. The type and extent of brain lesions were determined using cerebral imaging. Eighteen children had subnormal visual field function. The visual fields were severely restricted in six. The underlying brain lesions were malformation (n=7), white matter damage of immaturity (WMDI; n=13), and cortical-subcortical lesions (n=9). Visual field function could be correlated with the pattern of brain damage in children with cortical-subcortical lesions or extensive lesions caused by malformation or WMDI. Total homonymous hemianopia was common in the cortical-subcortical group but rare in children with malformation or WMDI. Five children had normal visual field function despite having malformation or WMDI involving parts of the brain usually encompassing the visual system. Visual field function may be preserved by plasticity of the immature