WorldWideScience

Sample records for age-related memory loss

  1. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  2. Memory Loss, Dementia, and Stroke: Implications for Rehabilitation of Older Adults with Age-Related Macular Degeneration

    Science.gov (United States)

    Warren, Mary

    2008-01-01

    Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…

  3. Evaluation of Age-Related Hearing Loss

    OpenAIRE

    2013-01-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide imp...

  4. Evaluation of age-related hearing loss.

    Science.gov (United States)

    Kim, Tae Su; Chung, Jong Woo

    2013-09-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide improved communication ability to users. But, simple auditory rehabilitation is ineffective in managing the central auditory processing disorder and the psychosocial problem of presbycusis. The evaluation of central auditory processing disorder and psychosocial disorder in presbycusis should not be overlooked while providing auditory rehabilitation.

  5. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

    Aging is a natural consequence of a society developing process. Although many adults retain good hearing as they aging, hearing loss related with age-presbycusis which can vary in severity from mild to substantial is common among elderly persons. There are a number of pathophysiological processes underlying age-related changes in the auditory system as well as in the central nervous systems. Many studies have been dedicated to the illustration of risk factors accumulating presbycusis such as heritability, environment factors, medical conditions, free radical (reactive oxygen species, ROS) and damage of mitochondrial DNA. Left untreated, presbycusis can not only lead sufferers to reduced quality of life, isolation, dependence and frustration, but also affect the healthy people around. These can be partly corrected using hearing aids, but it is not enough, more and more strategies of treatment based on the findings associating with presbycusis should be added rather than using single hearing aids. We review here the pathophysiology; heritability, susceptibility genes and other risk factors including environmental, medical, especially free radical (ROS) and damage of mitochondrial DNA; and some strategies of treatment, as well as promising rehabilitations associating with presbycusis.

  6. New Clues to Age-Related Hearing Loss

    Science.gov (United States)

    ... fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a harder time processing ... conversation, many older people chalk it up to hearing loss. But a new, small study finds that the ...

  7. Memory loss

    Science.gov (United States)

    A person with memory loss needs a lot of support. It helps to show the person familiar objects, music, or and photos or play familiar music. Write down when the person should take any medicine or do other ...

  8. KCNQ channels regulate age-related memory impairment.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  9. Mouse models of age-related mitochondrial neurosensory hearing loss.

    Science.gov (United States)

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  10. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  11. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals.......Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...

  12. Pathophysiology of age-related hearing loss (peripheral and central).

    Science.gov (United States)

    Lee, Kyu-Yup

    2013-09-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Extrinsic factors include noise, ototoxic medication and diet. However, presbycusis may not be related to the intrinsic and extrinsic factors separately. Presbycusis affects not only the physical, cognitive and emotional activities of patients, but also their social functioning. As a result, patients' quality of life deteriorates, compounded by various symptoms including depression, social isolation and lower self-esteem. Presbycusis is classified into six categories, as based on results of audiometric tests and temporal bone pathology, established by Schuknecht (1993): sensory, neural, metabolic or strial, cochlear conductive, mixed and indeterminate types. Among these, metabolic presbycusis is the mainstay of presbycusis types. Age-related changes also develop in the central hearing system. Functional decline of the central auditory system, caused by aging, reduces speech-understanding in noisy background and increase temporal processing deficits in gap-detection measures. This study reviews the literature on the age-related hearing loss.

  13. Age-related differences in working memory updating components.

    Science.gov (United States)

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.

  14. Activity loss and depression in age-related macular degeneration.

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    Rovner, Barry W; Casten, Robin J

    2002-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of severe vision loss in older persons and is associated with high rates of disability and depression. The authors evaluated 51 patients with bilateral AMD to investigate the interrelationships of disease severity, disability, and depression and focused on loss of valued activities as an emblematic disabling consequence of AMD. They characterized depression by the Center for Epidemiologic Studies-Depression (CES-D) score, a syndromal state based on the CES-D, and as a level of distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%) had loss of a valued, discretionary activity. They had worse visual acuity and more depressive symptoms and were represented in higher IAS levels than other subjects. Visual acuity was significantly correlated with IAS levels, but not with CES-D scores or syndromal depression. A regression model demonstrated that activity loss mediated the relationship between visual acuity and IAS level. Affective distress occurs in AMD, largely to the extent that valued activities are relinquished because of vision loss. IAS levels best illuminated this relationship, suggesting the value of this dimension of affective functioning in studies of the consequences of chronic disease.

  15. Age-related hearing loss increases cross-modal distractibility.

    Science.gov (United States)

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  16. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  17. Age-related loss of orexin/hypocretin neurons

    Science.gov (United States)

    Kessler, Brice A.; Stanley, Emily M.; Frederick-Duus, Danielle; Fadel, Jim

    2011-01-01

    Aging is associated with many physiological alterations—such as changes in sleep patterns, metabolism and food intake—suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3–4 months) and old (26–28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances. PMID:21262323

  18. Coping with Memory Loss

    Science.gov (United States)

    ... Consumers Home For Consumers Consumer Updates Coping With Memory Loss Share Tweet Linkedin Pin it More sharing ... a health professional. back to top What Causes Memory Loss? Anything that affects cognition—the process of ...

  19. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  20. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  1. Comparative study of oxidative stress in individuals with and without age related hearing loss

    Directory of Open Access Journals (Sweden)

    Vineeth VK

    2015-08-01

    Conclusion: We found an association between the level of Glutathione and Super Oxide Dismutase in age related hearing loss. Thus the serum Glutathione and Super Oxide Dismutase level can be used as a biomarker for the assessment of age related hearing loss. [Int J Res Med Sci 2015; 3(8.000: 2020-2023

  2. Age-related hearing loss: ear and brain mechanisms.

    Science.gov (United States)

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  3. Age-related differences in sleep-based memory consolidation: A meta-analysis.

    Science.gov (United States)

    Gui, Wen-Jun; Li, Hui-Jie; Guo, Yu-Hua; Peng, Peng; Lei, Xu; Yu, Jing

    2017-02-02

    A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory.

  4. An age-related deficit in spatial-feature reference memory in homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Flaim, Mary E; Carney, Samantha N; Bingman, Verner P

    2015-03-01

    Age-related memory decline in mammals has been well documented. By contrast, very little is known about memory decline in birds as they age. In the current study we trained younger and older homing pigeons on a reference memory task in which a goal location could be encoded by spatial and feature cues. Consistent with a previous working memory study, the results revealed impaired acquisition of combined spatial-feature reference memory in older compared to younger pigeons. Following memory acquisition, we used cue-conflict probe trials to provide an initial assessment of possible age-related differences in cue preference. Both younger and older pigeons displayed a similarly modest preference for feature over spatial cues.

  5. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    OpenAIRE

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rat...

  6. Age-related spatial working memory deficits in homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Hough, Gerald; Bingman, Verner P

    2014-12-01

    The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.

  7. Age-Related Hearing Loss: Quality of Care for Quality of Life

    Science.gov (United States)

    Li-Korotky, Ha-Sheng

    2012-01-01

    Age-related hearing loss (ARHL), known as presbycusis, is characterized by progressive deterioration of auditory sensitivity, loss of the auditory sensory cells, and central processing functions associated with the aging process. ARHL is the third most prevalent chronic condition in older Americans, after hypertension and arthritis, and is a…

  8. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    Science.gov (United States)

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

  9. Mechanisms of age-related decline in memory search across the adult life span.

    Science.gov (United States)

    Hills, Thomas T; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R

    2013-12-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information.

  10. Age-related effects on the neural correlates of autobiographical memory retrieval.

    Science.gov (United States)

    St Jacques, Peggy L; Rubin, David C; Cabeza, Roberto

    2012-07-01

    Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

  11. Age-related effects on the neural correlates of autobiographical memory retrieval

    Science.gov (United States)

    St. Jacques, Peggy L.; Rubin, David C.; Cabeza, Roberto

    2011-01-01

    Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and PFC underlie age-related reductions in episodic richness of the personal past. PMID:21190759

  12. Less efficient pattern separation may contribute to age-related spatial memory deficits

    Directory of Open Access Journals (Sweden)

    Heather M. Holden

    2012-05-01

    Full Text Available Spatial memory deficits have been well documented in older adults and may serve as an early indicator of mild cognitive impairment or Alzheimer’s disease in some individuals. Pattern separation is a critical mechanism for reducing potential interference among similar memory representations to enhance memory accuracy. A small but growing literature indicates that spatial pattern separation may become less efficient as a result of normal aging, possibly due to age-related changes in subregions of the hippocampus. This decreased efficiency in spatial pattern separation may be a critical processing deficit that could be a contributing factor to spatial memory deficits and episodic memory impairment associated with aging. The present paper will review recently published studies in humans, nonhuman primates, and rodents that have examined age-related changes in spatial pattern separation. The potential basic science, translational, and clinical implications from these studies are discussed to illustrate the need for future research to further examine the relationship between spatial pattern separation and brain changes associated with aging and neurodegenerative disease.

  13. Age-related Hearing Impairment and the Triad of Acquired Hearing Loss

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    Chao-Hui eYang

    2015-07-01

    Full Text Available Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss ¬¬displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI in human and animal models and address selected aspects of the commonality (or lack thereof of cellular responses in ARHI to drugs and noise.

  14. DRYAD and ADH: Further comments on explaining age-related differences in memory.

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    Naveh-Benjamin, Moshe; Smyth, Andrea C

    2016-02-01

    Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory.

  15. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    Directory of Open Access Journals (Sweden)

    Chatchada Sutalangka

    2013-01-01

    Full Text Available To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s are still required.

  16. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    Science.gov (United States)

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

  17. Middle ear impedance studies in elderly patients implications on age-related hearing loss

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    Olusola Ayodele Sogebi

    2015-04-01

    Full Text Available INTRODUCTION: Controversies arise with respect to functioning of the middle ear over time.OBJECTIVE: To assess changes in middle ear impedance that may be related to aging, and/or if there was an association of these changes with those of the inner ear in the elderly patients.METHODS: Cross-sectional, comparative study of elderly patients managed in ear, nose and throat clinics. A structured questionnaire was administered to obtain clinical information. Pure tone audiometry, tympanometry, and acoustic reflexes were performed. Comparative analyses were performed to detect intergroup differences between clinico-audiometric findings and middle ear measures, viz. tympanograms and acoustic reflexes.RESULTS: One hundred and three elderly patients participated in the study; 52.4% were male, averagely 70.0 ± 6.3 years old, age-related hearing loss in 59.2%, abnormal tympanograms in 39.3%, absent acoustic reflex in 37.9%. There was no association between age and gender in patients with abnormal tympanograms and absent acoustic reflex. Significantly more patients with different forms and grades of age-related hearing loss had abnormal tympanometry and absent acoustic reflex.CONCLUSION: Some abnormalities were observed in the impedance audiometric measures of elderly patients, which were significantly associated with parameters connected to age-related hearing loss.

  18. A four-component model of age-related memory change.

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    Healey, M Karl; Kahana, Michael J

    2016-01-01

    We develop a novel, computationally explicit, theory of age-related memory change within the framework of the context maintenance and retrieval (CMR2) model of memory search. We introduce a set of benchmark findings from the free recall and recognition tasks that include aspects of memory performance that show both age-related stability and decline. We test aging theories by lesioning the corresponding mechanisms in a model fit to younger adult free recall data. When effects are considered in isolation, many theories provide an adequate account, but when all effects are considered simultaneously, the existing theories fail. We develop a novel theory by fitting the full model (i.e., allowing all parameters to vary) to individual participants and comparing the distributions of parameter values for older and younger adults. This theory implicates 4 components: (a) the ability to sustain attention across an encoding episode, (b) the ability to retrieve contextual representations for use as retrieval cues, (c) the ability to monitor retrievals and reject intrusions, and (d) the level of noise in retrieval competitions. We extend CMR2 to simulate a recognition memory task using the same mechanisms the free recall model uses to reject intrusions. Without fitting any additional parameters, the 4-component theory that accounts for age differences in free recall predicts the magnitude of age differences in recognition memory accuracy. Confirming a prediction of the model, free recall intrusion rates correlate positively with recognition false alarm rates. Thus, we provide a 4-component theory of a complex pattern of age differences across 2 key laboratory tasks.

  19. Obesity and medicare expenditure: accounting for age-related height loss.

    Science.gov (United States)

    Onwudiwe, Nneka C; Stuart, Bruce; Zuckerman, Ilene H; Sorkin, John D

    2011-01-01

    To determine the relationship between BMI and Medicare expenditure for adults 65-years and older and determine whether this relationship changes after accounting for misclassification due to age-related height loss. Using a cross sectional study design, the relationship between BMI and fee-for-service Medicare expenditure was examined among beneficiaries who completed the Medicare Current Beneficiary Survey (MCBS) in 2002, were not enrolled in Medicare Health Maintenance Organization, had a self-reported height and weight, and were 65 and older (n = 7,706). Subjects were classified as underweight, normal weight, overweight, obese (obese I), and severely obese (obese II/III). To adjust BMI for the artifactual increase associated with age-related height loss, the reported height was transformed by adding the sex-specific age-associated height loss to the reported height in MCBS. The main outcome variable was total Medicare expenditure. There was a significant U-shaped pattern between unadjusted BMI and Medicare expenditure: underweight $4,581 (P accounting for height loss: underweight $4,640 (P cost is not found at "normal" BMI, but rather in overweight subjects with higher spending in the obese and underweight categories. Adjusting for loss-of-height with aging had little affect on cost estimates.

  20. Anti-apoptotic treatment in mouse models of age-related hearing loss

    Institute of Scientific and Technical Information of China (English)

    Fengchan Han; Oumei Wang; Quanxiang Cai

    2016-01-01

    Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear. Although the mechanisms leading to genetic hearing loss are not completely understood, caspase-family proteases function as important signals in the inner ear pathology. It is now accepted that mouse models are the best tools to study the mechanism of genetic hearing loss or AHL. Here, we provide a brief review of recent studies on hearing improvement in mouse models of AHL by anti-apoptotic treatment.

  1. Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

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    Kenji Watanabe

    2014-01-01

    Full Text Available Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/− mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice.

  2. Aging and associative recognition: A view from the DRYAD model of age-related memory deficits.

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    Benjamin, Aaron S

    2016-02-01

    How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart.

  3. A clinical study of age related hearing loss among diabetes patients

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    Sheetal Krishnappa

    2014-01-01

    Full Text Available Background: Age related hearing loss is one of the most common chronic health conditions affecting the elderly people. With aging, risk of presbycusis and diabetes increases. Our study aims at evaluating auditory dysfunction in patients with diabetes mellitus aged above 50 years as compared to non-diabetic patient. We also tried to find the relation between duration of diabetes and severity of hearing loss and whether HbA1c and blood sugars levels affected the type and severity of hearing loss. Materials and Methods: A cross-sectional study on 106 patients with type 2 diabetes mellitus and 90 non-diabetic patients with age and sex matched (controls was carried out during November 2011 to October 2013. All patients were evaluated for hearing loss by subjecting to pure tone audiometry and blood investigations like glycated hemoglobin, fasting and postprandial blood sugars and serum creatinine levels. Results: A prevalence of 73% hearing loss was seen in diabetics. The degree of hearing loss increased with age. There was bilateral progressive sensory neural hearing loss with right sloping curve in both diabetics as well as controls but with significantly (P < 0.001 higher loss in diabetics (at 4 KHz and 8 KHz. A significant relationship between duration of the diabetes, HbA1c and severity of hearing loss was observed. Conclusion: Diabetes mellitus was associated with higher hearing loss compared to presbycusis and hearing threshold was seen to affect all frequencies, but significantly the higher frequencies in diabetics. As duration of diabetes increased, the severity also increased. Poorer the HbA1c, more severe was the hearing loss.

  4. Classifying human audiometric phenotypes of age-related hearing loss from animal models.

    Science.gov (United States)

    Dubno, Judy R; Eckert, Mark A; Lee, Fu-Shing; Matthews, Lois J; Schmiedt, Richard A

    2013-10-01

    Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations ("audiometric phenotypes"). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for "exemplars" (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.

  5. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  6. Age-related hearing loss in sea lions and their scientists

    Science.gov (United States)

    Schusterman, Ronald J.; Southall, Brandon; Kastak, David; Reichmuth Kastak, Colleen

    2002-05-01

    Interest in the hearing capabilities of California sea lions (Zalophus californianus) was first stimulated by the echolocation hypothesis and more recently by rising concern about coastal noise pollution. During a series of audiometric tests, we measured the absolute hearing sensitivity of two sea lions and two of their human investigators. Aerial hearing curves for each subject were obtained with a go/no-go procedure and standard psychophysics. Additionally, underwater hearing curves were obtained for the sea lions using the same procedures. Underwater, the older sea lion (22-25 years of age) showed hearing losses relative to the younger sea lion (13-16 years) that ranged from 10 dB at lower frequencies to 50 dB near the upper frequency limit. The older sea lions' hearing losses in air were consistent with those measured underwater. The older human (69 years) tested also showed losses relative to the younger human (22 years). These differences ranged from 15 dB at lower frequencies up to 35 dB at the highest frequency tested. The results obtained in this study document age-related hearing losses in sea lions and humans. The findings are consistent with data on presbycusis in other mammalian species, showing that maximum hearing loss occurs at the highest frequencies.

  7. Medications for Memory Loss

    Science.gov (United States)

    ... by state Home > Alzheimer's Disease > Treatments > Medications for Memory Overview What Is Dementia? What Is Alzheimer's? Younger/ ... Interactive Tour Risk Factors Diagnosis Treatments Medications for Memory Treatments for Behavior For Sleep Changes Alternative Treatments ...

  8. Long-term treatment with aldosterone slows the progression of age-related hearing loss.

    Science.gov (United States)

    Halonen, Joshua; Hinton, Ashley S; Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-06-01

    Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL.

  9. Quantification of visual field loss in age-related macular degeneration.

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    Jennifer H Acton

    Full Text Available BACKGROUND: An evaluation of standard automated perimetry (SAP and short wavelength automated perimetry (SWAP for the central 10-2 visual field test procedure in patients with age-related macular degeneration (AMD is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. METHODS: 10-2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. RESULTS: Mean Deviation and Pattern Standard Deviation (PSD varied significantly with stage of disease in SAP (both p<0.001 and SWAP (both p<0.001, but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1° changed by -3.9 and -4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. CONCLUSIONS: Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD.

  10. Age-related differences in inhibitory control and memory updating in boys with Asperger syndrome.

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    Weiss, Elisabeth M; Gschaidbauer, Bianca; Kaufmann, Liane; Fink, Andreas; Schulter, Günter; Mittenecker, Erich; Papousek, Ilona

    2016-12-26

    Deficits in specific executive domains are highly prevalent in autism spectrum disorder; however, age-related improvements in executive functions (reflecting prefrontal maturational changes) have been reported even in individuals diagnosed with autism. The current study examined two components of cognitive flexibility (inhibition of prepotent responses and memory monitoring/updating) by using a random-motor-generation task (MPT) in a group of 23 boys with Asperger syndrome (AS) and 23 matched healthy controls. We found poorer inhibition and more repetitive responses in younger AS children solely, but comparable memory monitoring/updating skills across groups. Overall, our findings correspond well with previous studies and reveal that even in AS specific EFs may improve with age and, thus, call for a more differentiated view of executive (dys) function profiles in children diagnosed with AS. Tests such as the random-motor-generation task may help to disentangle more specific processes of executive deficits in autism spectrum disorder as compared to the more classical tests.

  11. Loss of peripheral right-ear advantage in age-related hearing loss.

    Science.gov (United States)

    Tadros, Sherif F; Frisina, Susan T; Mapes, Frances; Kim, SungHee; Frisina, D Robert; Frisina, Robert D

    2005-01-01

    In young adults with normal hearing, the right ear is more sensitive than the left to simple sounds (peripheral right-ear advantage) and to processing complex sounds such as speech (central right-ear advantage). In the present investigation, the effects of hearing loss and aging on this auditory asymmetry were examined at both peripheral and central levels. Audiograms and transient evoked otoacoustic emission (TEOAE) and distortion product otoacoustic emission amplitudes were used to assess cochlear function. The contralateral suppression of TEOAEs was measured to assess the medial olivocochlear efferent system. The Hearing in Noise Test (HINT; binaural speech) was conducted to assess higher central auditory function. A group of aged subjects with normal hearing (flat audiograms) were compared to a group of aged subjects with sloping audiograms (presbycusis). At the cochlear (peripheral) level, the normal hearing group showed significantly higher otoacoustic emission amplitudes for the right ear compared to the left ear, which is consistent with the right-ear dominance normally seen in young adults. However, this finding was reversed in the presbycusic group that showed higher left-ear emission amplitudes. At the brainstem level, the amplitudes of TEOAE contralateral suppression were small and no significant difference was found between the right and left ears in both groups. On the contrary, HINT results showed a continuous dominance of the right ear (left hemisphere) in both groups, which was consistent with previous reports showing that the right hemisphere is more affected by age than the left hemisphere.

  12. Aging-related gains and losses associated with word production in connected speech.

    Science.gov (United States)

    Dennis, Paul A; Hess, Thomas M

    2016-11-01

    Older adults have been observed to use more nonnormative, or atypical, words than younger adults in connected speech. We examined whether aging-related losses in word-finding abilities or gains in language expertise underlie these age differences. Sixty younger and 60 older adults described two neutral photographs. These descriptions were processed into word types, and textual analysis was used to identify interrupted speech (e.g., pauses), reflecting word-finding difficulty. Word types were assessed for normativeness, with nonnormative word types defined as those used by six (5%) or fewer participants to describe a particular picture. Accuracy and precision ratings were provided by another sample of 48 high-vocabulary younger and older adults. Older adults produced more interrupted and, as predicted, nonnormative words than younger adults. Older adults were more likely than younger adults to use nonnormative language via interrupted speech, suggesting a compensatory process. However, older adults' nonnormative words were more precise and trended for having higher accuracy, reflecting expertise. In tasks offering response flexibility, like connected speech, older adults may be able to offset instances of aging-related deficits by maximizing their expertise in other instances.

  13. Age-related positivity effects and autobiographical memory detail: evidence from a past/future source memory task.

    Science.gov (United States)

    Gallo, David A; Korthauer, Laura E; McDonough, Ian M; Teshale, Salom; Johnson, Elizabeth L

    2011-08-01

    This study investigated whether the age-related positivity effect strengthens specific event details in autobiographical memory. Participants retrieved past events or imagined future events in response to neutral or emotional cue words. Older adults rated each kind of event more positively than younger adults, demonstrating an age-related positivity effect. We next administered a source memory test. Participants were given the same cue words and tried to retrieve the previously generated event and its source (past or future). Accuracy on this source test should depend on the recollection of specific details about the earlier generated events, providing a more objective measure of those details than subjective ratings. We found that source accuracy was greater for positive than negative future events in both age groups, suggesting that positive future events were more detailed. In contrast, valence did not affect source accuracy for past events in either age group, suggesting that positive and negative past events were equally detailed. Although ageing can bias people to focus on positive aspects of experience, this bias does not appear to strengthen the availability of details for positive relative to negative past events.

  14. Association of Vision Loss in Glaucoma and Age-Related Macular Degeneration with IADL Disability

    Science.gov (United States)

    Hochberg, Chad; Maul, Eugenio; Chan, Emilie S.; Van Landingham, Suzanne; Ferrucci, Luigi; Friedman, David S.; Ramulu, Pradeep Y.

    2012-01-01

    Purpose. To determine if glaucoma and/or age-related macular degeneration (AMD) are associated with disability in instrumental activities of daily living (IADLs). Methods. Glaucoma subjects (n = 84) with bilateral visual field (VF) loss and AMD subjects (n = 47) with bilateral or severe unilateral visual acuity (VA) loss were compared with 60 subjects with normal vision (controls). Subjects completed a standard IADL disability questionnaire, with disability defined as an inability to perform one or more IADLs unassisted. Results. Disability in one or more IADLs was present in 18.3% of controls as compared with 25.0% of glaucoma subjects (P = 0.34) and 44.7% of AMD subjects (P = 0.003). The specific IADL disabilities occurring more frequently in both AMD and glaucoma subjects were preparing meals, grocery shopping, and out-of-home travelling (P AMD (odds ratio [OR] = 3.4, P = 0.02) but not glaucoma (OR = 1.4, P = 0.45) was associated with IADL disability. However, among glaucoma and control patients, the odds of IADL disability increased 1.6-fold with every 5 dB of VF loss in the better-seeing eye (P = 0.001). Additionally, severe glaucoma subjects (better-eye MD worse than −13.5 dB) had higher odds of IADL disability (OR = 4.2, P = 0.02). Among AMD and control subjects, every Early Treatment of Diabetic Retinopathy Study line of worse acuity was associated with a greater likelihood of IADL disability (OR = 1.3). Conclusions. VA loss in AMD and severe VF loss in glaucoma are associated with self-reported difficulties with IADLs. These limitations become more likely with increasing magnitude of VA or VF loss. PMID:22491415

  15. GRM7 variants associated with age-related hearing loss based on auditory perception.

    Science.gov (United States)

    Newman, Dina L; Fisher, Laurel M; Ohmen, Jeffrey; Parody, Robert; Fong, Chin-To; Frisina, Susan T; Mapes, Frances; Eddins, David A; Robert Frisina, D; Frisina, Robert D; Friedman, Rick A

    2012-12-01

    Age-related hearing impairment (ARHI), or presbycusis, is a common condition of the elderly that results in significant communication difficulties in daily life. Clinically, it has been defined as a progressive loss of sensitivity to sound, starting at the high frequencies, inability to understand speech, lengthening of the minimum discernable temporal gap in sounds, and a decrease in the ability to filter out background noise. The causes of presbycusis are likely a combination of environmental and genetic factors. Previous research into the genetics of presbycusis has focused solely on hearing as measured by pure-tone thresholds. A few loci have been identified, based on a best ear pure-tone average phenotype, as having a likely role in susceptibility to this type of hearing loss; and GRM7 is the only gene that has achieved genome-wide significance. We examined the association of GRM7 variants identified from the previous study, which used an European cohort with Z-scores based on pure-tone thresholds, in a European-American population from Rochester, NY (N = 687), and used novel phenotypes of presbycusis. In the present study mixed modeling analyses were used to explore the relationship of GRM7 haplotype and SNP genotypes with various measures of auditory perception. Here we show that GRM7 alleles are associated primarily with peripheral measures of hearing loss, and particularly with speech detection in older adults.

  16. Communicating with assistive listening devices and age-related hearing loss: Perceptions of older Australians.

    Science.gov (United States)

    Aberdeen, Lucinda; Fereiro, David

    2014-01-01

    Abstract Age-related hearing loss can impact adversely on the delivery of primary care and cannot necessarily be remedied by hearing aid technology. A study of 20 older Australians living in a Queensland retirement village and residential hostel complex was undertaken to investigate how communication might be advanced through an assistive listening device (ALD). Most participants were women aged over 85 years; almost all had hearing loss and wore hearing aids. Tests with an ALD found very high levels of satisfaction with understanding speech and sound quality amongst participants. However, few had heard previously of ALDs, all required individualised assistance to fit and use the device and rated ease of use less highly. The findings affirm those of previous studies that ALD technology has a role in communication for older hearing impaired people and for hearing rehabilitation. Its potential to enhance quality of life can be facilitated and promoted through nursing practice, but requires professional and consumer education so that it is not overlooked as a communication option.

  17. Can changes in eye movement scanning alter the age-related deficit in recognition memory?

    Directory of Open Access Journals (Sweden)

    Jessica P.K. Chan

    2011-05-01

    Full Text Available Older adults typically exhibit poorer face recognition compared to younger adults. These recognition differences may be due to underlying age-related changes in eye movement scanning. We examined whether older adults’ recognition could be improved by yoking their eye movements to those of younger adults. Participants studied younger and older faces, under free viewing conditions (bases, through a gaze-contingent moving window (own, or a moving window which replayed the eye movements of a base participant (yoked. During the recognition test, participants freely viewed the faces with no viewing restrictions. Own-age recognition biases were observed for older adults in all viewing conditions, suggesting that this effect occurs independently of scanning. Participants in the bases condition had the highest recognition accuracy, and participants in the yoked condition were more accurate than participants in the own condition. Among yoked participants, recognition did not depend on age of the base participant. These results suggest that successful encoding for all participants requires the bottom-up contribution of peripheral information, regardless of the locus of control of the viewer. Although altering the pattern of eye movements did not increase recognition, the amount of sampling of the face during encoding predicted subsequent recognition accuracy for all participants. Increased sampling may confer some advantages for subsequent recognition, particularly for people who have declining memory abilities.

  18. The ties to unbind: Age-related differences in feature (unbinding in working memory for emotional faces

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    Didem ePehlivanoglu

    2014-04-01

    Full Text Available In the present study, we investigated age-related differences in the processing of emotional stimuli. Specifically, we were interested in whether older adults would show deficits in unbinding emotional expression (i.e., either no emotion, happiness, anger, or disgust from bound stimuli (i.e., photographs of faces expressing these emotions, as a hyperbinding account of age-related differences in working memory would predict. Younger and older adults completed different N-Back tasks (side-by-side 0-Back, 1-Back, 2-Back under three conditions: match/mismatch judgments based on either the identity of the face (identity condition, the face’s emotional expression (expression condition, or both identity and expression of the face (binding condition. Both age groups performed more slowly and with lower accuracy in the expression condition than in the binding condition, indicating the presence of an unbinding process. This unbinding effect was more pronounced in older adults than in younger adults, but only in the 2-Back task. Thus, older adults seemed to have a specific deficit in unbinding in working memory, over and beyond age-related differences observed in perceptual processing (0-Back and attention/short-term memory (1-Back. Additionally, no age-related differences were found in accuracy in the 0-Back task, but such differences emerged in the 1-Back task, and were further magnified in the 2-Back task, indicating independent age-related differences in attention/short-term memory and working memory. Pupil dilation data confirmed that the attention/short-term memory version of the task (1-Back is more effortful in older adults than younger adults.

  19. Memory Loss and Retrieval

    Science.gov (United States)

    Reid, Ian

    2016-01-01

    Underlying the generally oblivious attitude of teachers and learners towards the past is insufficient respect for the role of memory in giving meaning to experience and access to knowledge. We shape our identity by making sense of our past and its relationship to present and future selves, a process that should be intensively cultivated when we…

  20. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    Science.gov (United States)

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  1. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    Science.gov (United States)

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (PLeptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  2. Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older adults

    NARCIS (Netherlands)

    Dullemeijer, C.; Verhoef, P.; Brouwer, I.A.; Kok, F.J.; Brummer, R.J.; Durga, J.

    2010-01-01

    Objectives: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in agerelated hearing loss. In this study we investigated whether plasma very long-chain n-3 po

  3. Sleep loss produces false memories.

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    Susanne Diekelmann

    Full Text Available People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",..., lacking the strongest common associate or theme word (here: "black". Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.

  4. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

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    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  5. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

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    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  6. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  7. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

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    Lovatel, Gisele Agustini; Elsner, Viviane Rostirola; Bertoldi, Karine; Vanzella, Cláudia; Moysés, Felipe Dos Santos; Vizuete, Adriana; Spindler, Christiano; Cechinel, Laura Reck; Netto, Carlos Alexandre; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-03-01

    It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-β and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.

  8. Age-related effects on verbal and visuospatial memory are mediated by theta and alpha II rhythms.

    Science.gov (United States)

    Reichert, Johanna Louise; Kober, Silvia Erika; Witte, Matthias; Neuper, Christa; Wood, Guilherme

    2016-01-01

    Both electrical brain activity during rest and memory functions change across the lifespan. Moreover, electrical brain activity is associated with memory functions. However, the interplay between all these effects has been investigated only scarcely. The present study investigated the extent to which the power of resting-state electroencephalographic (EEG) frequencies mediates the impact of aging on verbal and visuospatial memory. Seventy healthy participants with 22 to 83years of age completed a visuospatial and verbal learning and memory test and provided eyes-open and eyes-closed resting-state EEG data. Robust age-related effects on behavioral and EEG data were observed. Mediation analyses showed that the relative power of the theta (4-8Hz) frequency band in fronto-central locations partly explained the negative age-related effect on delayed recall in the verbal memory task. The relative power of the alpha II (10-12Hz) frequency band in mainly parietal locations partly explained the negative impact of age on immediate and delayed recall in the visuospatial task. Results indicate that spontaneous brain activity carries specific information about aging processes and predicts the level of competence in verbal and visuospatial memory tasks.

  9. Auditory perceptual learning in adults with and without age-related hearing loss

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    Hanin eKarawani

    2016-02-01

    Full Text Available Introduction: Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL. Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL.Methods: 56 listeners (60-72 y/o, 35 participants with ARHL and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training and no-training group. Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1 Speech-in-noise (2 time compressed speech and (3 competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results: Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions: ARHL did not preclude auditory perceptual learning but there was little generalization to

  10. Auditory Perceptual Learning in Adults with and without Age-Related Hearing Loss

    Science.gov (United States)

    Karawani, Hanin; Bitan, Tali; Attias, Joseph; Banai, Karen

    2016-01-01

    Introduction : Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL). Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL. Methods : Fifty-six listeners (60–72 y/o), 35 participants with ARHL, and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training, and no-training group). Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1) Speech-in-noise, (2) time compressed speech, and (3) competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results : Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions : ARHL did not preclude auditory perceptual learning but there was little generalization to

  11. Age-related hearing loss and ear morphology affect vertical but not horizontal sound-localization performance

    NARCIS (Netherlands)

    Otte, R.J.; Agterberg, M.J.H.; Wanrooij, M.M. van; Snik, A.F.M.; Opstal, A.J. van

    2013-01-01

    Several studies have attributed deterioration of sound localization in the horizontal (azimuth) and vertical (elevation) planes to an age-related decline in binaural processing and high-frequency hearing loss (HFHL). The latter might underlie decreased elevation performance of older adults. However,

  12. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    Science.gov (United States)

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  13. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    Science.gov (United States)

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

  14. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

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    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  15. Memory Loss: 7 Tips to Improve Your Memory

    Science.gov (United States)

    ... re not alone. Everyone forgets things occasionally. Still, memory loss is nothing to take lightly. Although there are no guarantees when it comes to preventing memory loss or dementia, certain activities might help. Consider ...

  16. Age-related changes of frontal-midline theta is predictive of efficient memory maintenance.

    Science.gov (United States)

    Kardos, Z; Tóth, B; Boha, R; File, B; Molnár, M

    2014-07-25

    Frontal areas are thought to be the coordinators of working memory processes by controlling other brain areas reflected by oscillatory activities like frontal-midline theta (4-7 Hz). With aging substantial changes can be observed in the frontal brain areas, presumably leading to age-associated changes in cortical correlates of cognitive functioning. The present study aimed to test whether altered frontal-midline theta dynamics during working memory maintenance may underlie the capacity deficits observed in older adults. 33-channel EEG was recorded in young (18-26 years, N=20) and old (60-71 years, N=16) adults during the retention period of a visual delayed match-to-sample task, in which they had to maintain arrays of 3 or 5 colored squares. An additional visual odd-ball task was used to be able to measure the electrophysiological indices of sustained attentional processes. Old participants showed reduced frontal theta activity during both tasks compared to the young group. In the young memory maintenance-related frontal-midline theta activity was shown to be sensitive both to the increased memory demands and to efficient subsequent memory performance, whereas the old adults showed no such task-related difference in the frontal theta activity. The decrease of frontal-midline theta activity in the old group indicates that cerebral aging may alter the cortical circuitries of theta dynamics, thereby leading to age-associated decline of working memory maintenance function.

  17. Age-related memory impairment is associated with disrupted multivariate epigenetic coordination in the hippocampus.

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    James F Castellano

    Full Text Available Mounting evidence linking epigenetic regulation to memory-related synaptic plasticity raises the possibility that altered chromatin modification dynamics might contribute to age-dependent cognitive decline. Here we show that the coordinated orchestration of both baseline and experience-dependent epigenetic regulation seen in the young adult hippocampus is lost in association with cognitive aging. Using a well-characterized rat model that reliably distinguishes aged individuals with significant memory impairment from others with normal memory, no single epigenetic mark or experience-dependent modification in the hippocampus uniquely predicted differences in the cognitive outcome of aging. The results instead point to a multivariate pattern in which modification-specific, bidirectional chromatin regulation is dependent on recent behavioral experience, chronological age, cognitive status, and hippocampal region. Whereas many epigenetic signatures were coupled with memory capacity among young adults and aged rats with preserved cognitive function, such associations were absent among aged rats with deficits in hippocampal memory. By comparison with the emphasis in current preclinical translational research on promoting chromatin modifications permissive for gene expression, our findings suggest that optimally successful hippocampal aging may hinge instead on enabling coordinated control across the epigenetic landscape.

  18. Age-related hearing loss in dogs and treatment with Vibrant Soundbridge middle ear implant

    NARCIS (Netherlands)

    Haar, Gert ter

    2010-01-01

    Hearing loss is a common disorder in many breeds of dogs and auditory dysfunction and its clinical consequences can vary from mild to severe. Dogs with bilateral hearing loss are unable to anticipate dangers such as motor vehicles and they may consequently fall victim to serious or fatal injury. It

  19. The significance of caudate volume for age-related associative memory decline.

    Science.gov (United States)

    Bauer, E; Toepper, M; Gebhardt, H; Gallhofer, B; Sammer, G

    2015-10-05

    Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain.

  20. Similarity-based interference in a working memory numerical updating task: age-related differences between younger and older adults.

    Science.gov (United States)

    Pelegrina, Santiago; Borella, Erika; Carretti, Barbara; Lechuga, M Teresa

    2012-01-01

    Similarity among representations held simultaneously in working memory (WM) is a factor which increases interference and hinders performance. The aim of the current study was to investigate age-related differences between younger and older adults in a working memory numerical updating task, in which the similarity between information held in WM was manipulated. Results showed a higher susceptibility of older adults to similarity-based interference when accuracy, and not response times, was considered. It was concluded that older adults' WM difficulties appear to be due to the availability of stored information, which, in turn, might be related to the ability to generate distinctive representations and to the process of binding such representations to their context when similar information has to be processed in WM.

  1. Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity

    Science.gov (United States)

    Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.

    2007-01-01

    Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774

  2. Validating Age-Related Functional Imaging Changes in Verbal Working Memory with Acute Stroke

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    Timothy B. Meier

    2011-01-01

    Full Text Available Functional imaging studies consistently find that older adults recruit bilateral brain regions in cognitive tasks that are strongly lateralized in younger adults, a characterization known as the Hemispheric Asymmetry Reduction in Older Adults model. While functional imaging displays what brain areas are active during tasks, it cannot demonstrate what brain regions are necessary for task performance. We used behavioral data from acute stroke patients to test the hypothesis that older adults need both hemispheres for a verbal working memory task that is predominantly left-lateralized in younger adults. Right-handed younger (age ≥ 50, n = 7 and older adults (age > 50, n = 21 with acute unilateral stroke, as well as younger (n = 6 and older (n = 13 transient ischemic attack (TIA patients, performed a self-paced verbal item-recognition task. Older patients with stroke to either hemisphere had a higher frequency of deficits in the verbal working memory task compared to older TIA patients. Additionally, the deficits in older stroke patients were mainly in retrieval time while the deficits in younger stroke patients were mainly in accuracy. These data suggest that bihemispheric activity is necessary for older adults to successfully perform a verbal working memory task.

  3. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    Science.gov (United States)

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  4. Age-Related Deficits in Spatial Memory and Hippocampal Spines in Virgin, Female Fischer 344 Rats

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    Victoria N. Luine

    2011-01-01

    Full Text Available Effects of aging on memory and brain morphology were examined in aged, 21-month-old, and young, 4-month-old, Fischer 344 female rats. Spatial memory was assessed using the object placement task, and dendritic spine density was determined on pyramidal neurons in the hippocampus following Golgi impregnation. Consistent with previous studies, aged females showed poorer object placement performance than young subjects. Young subjects significantly discriminated the location of objects with a 1.5-hour intertrial delay while aged subjects did not. Spine density of basal dendrites on CA1 pyramidal cells was 16% lower in the aged subjects as compared to the young subjects. No differences in spine density were found between young and aged subjects in basal dendrites of CA1 or in either dendritic field of CA3 pyramidal neurons. Thus, decreased hippocampal CA1 dendritic spine density in aged rats may contribute to poorer spatial memory as compared to young rats. The possibility that the neuroplastic changes observed in this study may pertain only to female subjects having had a specific set of life experiences is discussed. Different factors, such as reproductive status, diet, and handling may contribute to neuroplasticity of the brain during aging; however, this view requires further examination.

  5. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  6. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    Science.gov (United States)

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

  7. Effects of Age and Age-Related Hearing Loss on the Brain

    Science.gov (United States)

    Tremblay, Kelly; Ross, Bernhard

    2007-01-01

    It is well documented that aging adversely affects the ability to perceive time-varying acoustic cues. Here we review how physiological measures are being used to explore the effects of aging (and concomitant hearing loss) on the neural representation of temporal cues. Also addressed are the implications of current research findings on the…

  8. Memory Loss: When to Seek Help

    Science.gov (United States)

    Memory loss: When to seek help A number of conditions — not only Alzheimer's disease — can cause memory loss in older adults. Getting a prompt diagnosis ... a person you just met? Some degree of memory problems, as well as a modest decline in ...

  9. Physical activity as intervention for age-related loss of muscle mass and function

    DEFF Research Database (Denmark)

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde

    2016-01-01

    to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative......INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known...... and cognitive function, mental well-being, health-related quality of life and brain morphology. METHODS AND ANALYSIS: The study includes 450 home-dwelling men and women (62-70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate...

  10. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study.

    Science.gov (United States)

    Brautigam, M R; Blommaert, F A; Verleye, G; Castermans, J; Jansen Steur, E N; Kleijnen, J

    1998-12-01

    A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising

  11. Age-related loss of calcium binding proteins in rabbit hippocampus

    OpenAIRE

    deJong, GI; Naber, PA; VANDERZEE, EA; Thompson, LT; Disterhoft, JF; Luiten, PGM

    1996-01-01

    Using immunocytochemistry hippocampal levels of the calcium binding proteins calbindin 28K (CB) and parvalbumin (PV) was studied in young (1 month) to very old (60 month) Albino rabbits. Young (3 month) and senescent (30 month) Wistar rats were also examined to compare the distribution and age dependency of PV and CB in both species. The distribution of PV-ir is similar in the rabbit and rat hippocampus. Aging in both species yielded a small loss of PV-ir in axon terminals. The presence of CB...

  12. Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available MicroRNAs (miRNAs, a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC, the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL, a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.

  13. Likely Age-Related Hearing Loss (Presbycusis) in a Stranded Indo-Pacific Humpback Dolphin (Sousa chinensis).

    Science.gov (United States)

    Li, Songhai; Wang, Ding; Wang, Kexiong; Hoffmann-Kuhnt, Matthias; Fernando, Nimal; Taylor, Elizabeth A; Lin, Wenzhi; Chen, Jialin; Ng, Timothy

    2016-01-01

    The hearing of a stranded Indo-Pacific humpback dolphin (Sousa chinensis) in Zhuhai, China, was measured. The age of this animal was estimated to be ~40 years. The animal's hearing was measured using a noninvasive auditory evoked potential (AEP) method. The results showed that the high-frequency hearing cutoff frequency of the studied dolphin was ~30-40 kHz lower than that of a conspecific younger individual ~13 year old. The lower high-frequency hearing range in the older dolphin was explained as a likely result of age-related hearing loss (presbycusis).

  14. Shortening-induced torque depression in old men: implications for age-related power loss.

    Science.gov (United States)

    Power, Geoffrey A; Makrakos, Demetri P; Stevens, Daniel E; Herzog, Walter; Rice, Charles L; Vandervoort, Anthony A

    2014-09-01

    Following active muscle shortening, the steady-state isometric torque at the final muscle length is lower than the steady-state torque obtained for a purely isometric contraction at that same final muscle length. This well-documented property of skeletal muscle is termed shortening-induced torque depression (TD). Despite many investigations into the mechanisms of weakness and power loss in old age, the influence of muscle shortening on the history dependence of isometric torque production remains to be elucidated. Thus, it is unclear whether older adults are disadvantaged for torque and power production following a dynamic shortening contraction. The purpose of this study was to evaluate shortening-induced TD in older adults, and to determine whether shortening-induced TD is related to power loss. Maximal voluntary isometric dorsiflexion contractions (MVC; 10s) in 8 young (25.5±3.7years) and 9 old (76.1±5.4years) men were performed on a HUMAC NORM dynamometer as a reference, and then again following an active shortening of 40° joint excursion (40°PF-0°PF) at angular velocities of 15°/s and 120°/s. Work and instantaneous power were derived during shortening. Shortening-induced TD was calculated and expressed as a percentage by determining the mean torque value over 1s during the isometric steady state of the MVC following shortening, divided by the mean torque value for the same 1s time period during the isometric reference MVC. To assess muscle activation, electromyography (root mean square; EMGRMS) of the tibialis anterior (TA) and soleus (SOL) was calculated at identical time points used in assessing shortening-induced TD, and voluntary activation (VA) was assessed using the interpolated twitch technique. Old were 18% weaker than young for MVC, and ~40% less powerful for 15°/s and 120°/s of shortening. Old produced 37% and 21% less work for 15°/s and 120°/s than young, respectively. Furthermore, old experienced 60% and 70% greater shortening-induced TD

  15. Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone.

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    Henry Todd

    Full Text Available Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an

  16. Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis).

    Science.gov (United States)

    Naldi, Arianne Monge; Belfrage, Celina; Jain, Neha; Wei, Eric T; Martorell, Belén Canto; Gassmann, Max; Vogel, Johannes

    2015-12-01

    So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50-80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice.

  17. Age-related Hearing Loss: GABA, Nicotinic Acetylcholine and NMDA Receptor Expression Changes in Spiral Ganglion Neurons of the Mouse

    Science.gov (United States)

    Tang, Xiaolan; Zhu, Xiaoxia; Ding, Bo; Walton, Joseph P.; Frisina, Robert D.; Su, Jiping

    2014-01-01

    Age-related hearing loss – presbycusis – is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate gamma-amino butyric acid A (GABAA) receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative RT-PCR techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40 dB from 3–48 kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40 dB from 6–49 kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. Spiral ganglion neuron (SGN) density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1 amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss. PMID:24316061

  18. Age related differences in dynamics of specific memory B cell populations after clinical pertussis infection.

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    Inonge van Twillert

    Full Text Available For a better understanding of the maintenance of immune mechanisms to Bordetella pertussis (Bp in relation to age, we investigated the dynamic range of specific B cell responses in various age-groups at different time points after a laboratory confirmed pertussis infection. Blood samples were obtained in a Dutch cross sectional observational study from symptomatic pertussis cases. Lymphocyte subpopulations were phenotyped by flowcytometry before and after culture. Memory B (Bmem cells were differentiated into IgG antibody secreting cells (ASC by polyclonal stimulation and detected by an ELISPOT assay specific for pertussis antigens pertussis toxin (Ptx, filamentous haemagglutinin (FHA and pertactin (Prn. Bp antigen specific IgG concentrations in plasma were determined using multiplex technology. The majority of subjects having experienced a clinical pertussis episode demonstrated high levels of both Bp specific IgG and Bmem cell levels within the first 6 weeks after diagnosis. Significantly lower levels were observed thereafter. Waning of cellular and humoral immunity to maintenance levels occurred within 9 months after antigen encounter. Age was found to determine the maximum but not base-line frequencies of Bmem cell populations; higher levels of Bmem cells specific for Ptx and FHA were reached in adults and (pre- elderly compared to under-fours and schoolchildren in the first 6 weeks after Bp exposure, whereas not in later phases. This age effect was less obvious for specific IgG levels. Nonetheless, subjects' levels of specific Bmem cells and specific IgG were weakly correlated. This is the first study to show that both age and closeness to last Bp encounter impacts the size of Bp specific Bmem cell and plasma IgG levels.

  19. Age-related changes in working memory during sentence comprehension: an fMRI study.

    Science.gov (United States)

    Grossman, Murray; Cooke, Ayanna; DeVita, Chris; Alsop, David; Detre, John; Chen, Willis; Gee, James

    2002-02-01

    Sentence comprehension declines with age, but the neural basis for this change is unclear. We monitored regional brain activity in 13 younger subjects and 11 healthy seniors matched for sentence comprehension accuracy while they answered a simple probe about written sentences. The sentences varied in their grammatical features (subject-relative vs object-relative subordinate clause) and their verbal working memory (WM) demands (short vs long antecedent noun-gap linkage). We found that young and senior subjects both recruit a core written sentence processing network, including left posterolateral temporal and bilateral occipital cortex for all sentences, and ventral portions of left inferior frontal cortex for object-relative sentences with a long noun-gap linkage. Differences in activation patterns for seniors compared to younger subjects were due largely to changes in brain regions associated with a verbal WM network. While seniors had less left parietal recruitment than younger subjects, left premotor cortex, and dorsal portions of left inferior frontal cortex showed greater activation in seniors compared to younger subjects. Younger subjects recruited right posterolateral temporal cortex for sentences with a long noun-gap linkage. Seniors additionally recruited right parietal cortex for this sentence-specific form of WM. Our findings are consistent with the hypothesis that the neural basis for sentence comprehension includes dissociable but interactive large-scale neural networks supporting core written sentence processes and related cognitive resources involved in WM. Seniors with good comprehension appear to up-regulate portions of the neural substrate for WM during sentence processing to achieve comprehension accuracy that equals young subjects.

  20. Age-related striatal BOLD changes without changes in behavioral loss aversion

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    Hans C Breiter

    2015-04-01

    Full Text Available Loss aversion (LA, the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years, or of the state of older age (e.g., past age 65 years. We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI to examine the ventral striatum/nucleus accumbens (VS/NAc response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1 the VS/NAc being a central region for reward/aversion processing, (2 its activation to both positive and negative stimuli, (3 its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS of the VS/NAc to avoidance responses (negative valuations relative to approach responses (positive valuations with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task.

  1. Auditory efferent feedback system deficits precede age-related hearing loss: contralateral suppression of otoacoustic emissions in mice.

    Science.gov (United States)

    Zhu, Xiaoxia; Vasilyeva, Olga N; Kim, Sunghee; Jacobson, Michael; Romney, Joshua; Waterman, Marjorie S; Tuttle, David; Frisina, Robert D

    2007-08-10

    The C57BL/6J mouse has been a useful model of presbycusis, as it displays an accelerated age-related peripheral hearing loss. The medial olivocochlear efferent feedback (MOC) system plays a role in suppressing cochlear outer hair cell (OHC) responses, particularly for background noise. Neurons of the MOC system are located in the superior olivary complex, particularly in the dorsomedial periolivary nucleus (DMPO) and in the ventral nucleus of the trapezoid body (VNTB). We previously discovered that the function of the MOC system declines with age prior to OHC degeneration, as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAEs) in humans and CBA mice. The present study aimed to determine the time course of age changes in MOC function in C57s. DPOAE amplitudes and CS of DPOAEs were collected for C57s from 6 to 40 weeks of age. MOC responses were observed at 6 weeks but were gone at middle (15-30 kHz) and high (30-45 kHz) frequencies by 8 weeks. Quantitative stereological analyses of Nissl sections revealed smaller neurons in the DMPO and VNTB of young adult C57s compared with CBAs. These findings suggest that reduced neuron size may underlie part of the noteworthy rapid decline of the C57 efferent system. In conclusion, the C57 mouse has MOC function at 6 weeks, but it declines quickly, preceding the progression of peripheral age-related sensitivity deficits and hearing loss in this mouse strain.

  2. Working memory in middle-aged males: age-related brain activation changes and cognitive fatigue effects.

    Science.gov (United States)

    Klaassen, Elissa B; Evers, Elisabeth A T; de Groot, Renate H M; Backes, Walter H; Veltman, Dick J; Jolles, Jelle

    2014-02-01

    We examined the effects of aging and cognitive fatigue on working memory (WM) related brain activation using functional magnetic resonance imaging. Age-related differences were investigated in 13 young and 16 middle-aged male school teachers. Cognitive fatigue was induced by sustained performance on cognitively demanding tasks (compared to a control condition). Results showed a main effect of age on left dorsolateral prefrontal and superior parietal cortex activation during WM encoding; greater activation was evident in middle-aged than young adults regardless of WM load or fatigue condition. An interaction effect was found in the dorsomedial prefrontal cortex (DMPFC); WM load-dependent activation was elevated in middle-aged compared to young in the control condition, but did not differ in the fatigue condition due to a reduction in activation in middle-aged in contrast to an increase in activation in the young group. These findings demonstrate age-related activation differences and differential effects of fatigue on activation in young and middle-aged adults.

  3. Age-related differences in memory expression during infancy: using eye-tracking to measure relational memory in 6- and 12-month-olds.

    Science.gov (United States)

    Richmond, Jenny L; Power, Jessica

    2014-09-01

    Relational memory, or the ability to bind components of an event into a network of linked representations, is a primary function of the hippocampus. Here we extend eye-tracking research showing that infants are capable of forming memories for the relation between arbitrarily paired scenes and faces, by looking at age-related changes in relational memory over the first year of life. Six- and 12-month-old infants were familiarized with pairs of faces and scenes before being tested with arrays of three familiar faces that were presented on a familiar scene. Preferential looking at the face that matches the scene is typically taken as evidence of relational memory. The results showed that while 6-month-old showed very early preferential looking when face/scene pairs were tested immediately, 12-month-old did not exhibit evidence of relational memory either immediately or after a short delay. Theoretical implications for the functional development of the hippocampus and practical implications for the use of eye tracking to measure memory during early life are discussed.

  4. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Sandrine eVieillard

    2013-10-01

    Full Text Available There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for music. In the present study, eighteen older (60-84 years and eighteen younger (19-24 years listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard, et al., 2008 while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a reported a stronger emotional reactivity for happiness than other emotion categories, (b showed an increased zygomatic activity for scary stimuli, (c were more likely to falsely recognize happy music, and (d showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.

  5. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study.

    Science.gov (United States)

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60-84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.

  6. Age-related differences in cortical activity during a visuo-spatial working memory task with facial stimuli.

    Directory of Open Access Journals (Sweden)

    Flávia Schechtman Belham

    Full Text Available Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA are expected to better recall negative events (Negativity Bias Hypothesis, older adults (OA tend to focus on positive stimuli (Positivity Effect Hypothesis. This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males and 25 OA (14 males, all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage, while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and

  7. Perfil lipídico de la sordera ligada al envejecimiento Lipid profile and hearing-loss aged-related

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    C. Martín Villares

    2005-02-01

    Full Text Available Objetivo y antecedentes: La sordera ligada al envejecimiento es la causa más frecuente de sordera a partir de los 65 años, pero su patogenia es aún mal conocida. El objetivo de este estudio es valorar el impacto de la hiperlipemia en su patogenia. Ámbito del estudio: Población mayor de 65 años del área de Salud de El Bierzo. Pacientes: Incluimos en el estudio 180 pacientes con hipoacusia neurosensorial bilateral, sin antecedentes de patología renal, neurológica, tiroidea o de oído medio. Intervenciones: Se realizó audiometría tonal y estudio de lípidos plasmáticos (colesterol, HDL, LDL y triglicéridos. Se utilizan métodos estadísticos. Resultados: Los más destacados fueron: 1 el 71% de los pacientes presentaban niveles altos de lípidos en sangre, sobre todo las mujeres entre 65-69 años (media 256 mg/dl; 2 los hombres entre 65-69 años presentaban un alto índice aterogénico (media 5,27; 3 los pacientes con hiperlipemia presentaban peor audición (p Objectives/hypothesis: Presbycusis is the most prevalent cause of hearing-loss in the older, but pathogenesis is not well-know. The premise of this study is that hyperlipemia increase risk of age-related hearing-loss. Patients and methods: 180 patient more than 65 years-old were studied. All patients had bilateral hearing-loss and no renal, neurological, thyriod or middle-ear pathology. We explored serum levels of cholesterol, HDL, LDL and triglycerides. We performed tonal audimetry in all patients. Results: The 71% of patients has hypercholesteremia and the higest serum levels were detected in 65-69 yearsold men (mean media 5,27. Patients with hypercholesteremia had worse hearing-loss than patients with normal lipid serum levels (p < .05. Conclusions: Our study sugest that hypercholesteremia are associated to age-related hearing-loss, possibly by an atherosclerosis mechanism.

  8. Cognitive self-consciousness--a predictor of increased anxiety following first-time diagnosis of age-related hearing loss.

    Science.gov (United States)

    Mohlman, Jan

    2009-03-01

    This study tested prospective models of anxiety and depression following a first time diagnosis of age-related hearing loss, also known as presbycusis, which is one of the most common and disabling health problems in the world. The predictor of interest was cognitive self-consciousness (CSC; Cartwright-Hatton & Wells (1997). Beliefs about worry and intrusions: The Meta-Cognitions Questionnaire and its correlates. Journal of Anxiety Disorders, 11, 276-279.), or the tendency to closely attend to and monitor the content and process of one's own thoughts. Sixty-seven older adults were assessed at a university-based audiology clinic at three timepoints: at the time of diagnosis (T1), six (T2), and 12 months later (T3). Measures of anxiety, depression, and CSC were collected. It was hypothesized that a subset of older adults with hearing loss would report increased CSC at T2. Additionally, the interaction of CSC and anxiety and depression symptoms at T2 was expected to predict significant variance in measures of anxiety and depression at T3, even after baseline levels of distress were controlled in regression models. Finally, it was hypothesized that consistent use of a hearing aid by T3 would act as a palliative to reduce distress in response to hearing loss at T3. Results were partially consistent with hypotheses and point to a new direction in preventing anxiety and depression following a first time diagnosis of presbycusis.

  9. Untreated sleep-disordered breathing: links to aging-related decline in sleep-dependent memory consolidation.

    Directory of Open Access Journals (Sweden)

    Ina Djonlagic

    Full Text Available BACKGROUND: Increasing age is associated with a decline in cognition and motor skills, while at the same time exacerbating one's risk of developing obstructive sleep apnea (OSA. OSA-related cognitive deficits are highly prevalent and can affect various memory systems including overnight memory consolidation on a motor sequence task. Thus, the aim of our study was to examine the effect of aging on sleep-dependent motor memory consolidation in patients with and without OSA. METHODS: We studied 44 patients (19-68 years who had been referred by a physician for a baseline polysomnography (PSG evaluation. Based on their PSG, patients were assigned either to the OSA group (AHI>5/h, or control (Non-OSA group (AHI<5/h. All subjects performed the Psychomotor Vigilance Task (PVT and the Motor Sequence Learning Task (MST in the evening and again in the morning after their PSG. RESULTS: Despite similar learning in the evening, OSA subjects showed significantly less overnight improvement on the MST, both for immediate (OSA -2.7% ± 2.8% vs. controls 12.2% ± 3.5%; p = 0.002 and plateau improvement (OSA 4.9% ± 2.3% vs. controls 21.1%± 4.0%; p = 0.001. Within the OSA group, there was a significant negative correlation between overnight MST improvement and age (r(2 = 0.3; p = 0.01, an effect that was not observed in the Non-OSA group (r(2 = 0.08; p = 0.23. CONCLUSIONS: Consistent with previous research, healthy sleepers demonstrated a higher degree of sleep-dependent overnight improvement on the MST, an effect not mitigated by increasing age. However, the presence of untreated obstructive sleep apnea is associated with an aging-related cognitive deficit, otherwise not present in individuals without OSA. As other research has linked the presence of OSA to a higher likelihood of developing dementia, future studies are necessary to examine if the inhibition of memory consolidation is tied to the onset of neurodegenerative disease.

  10. Age-related hearing loss: aquaporin 4 gene expression changes in the mouse cochlea and auditory midbrain.

    Science.gov (United States)

    Christensen, Nathan; D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D

    2009-02-01

    Presbycusis -- age-related hearing loss, is the number one communication disorder, and one of the top three chronic medical conditions of our aged population. Aquaporins, particularly aquaporin 4 (Aqp4), are membrane proteins with important roles in water and ion flux across cell membranes, including cells of the inner ear and pathways of the brain used for hearing. To more fully understand the biological bases of presbycusis, 39 CBA mice, a well-studied animal model of presbycusis, underwent non-invasive hearing testing as a function of sound frequency (auditory brainstem response -- ABR thresholds, and distortion-product otoacoustic emission -- DPOAE magnitudes), and were clustered into four groups based on age and hearing ability. Aqp4 gene expression, as determined by genechip microarray analysis and quantitative real-time PCR, was compared to the young adult control group in the three older groups: middle aged with good hearing, old age with mild presbycusis, and old age with severe presbycusis. Linear regression and ANOVA showed statistically significant changes in Aqp4 gene expression and ABR and DPOAE hearing status in the cochlea and auditory midbrain -- inferior colliculus. Down-regulation in the cochlea was seen, and an initial down-, then up-regulation was discovered for the inferior colliculus Aqp4 expression. It is theorized that these changes in Aqp4 gene expression represent an age-related disruption of ion flux in the fluids of the cochlea that are responsible for ionic gradients underlying sound transduction in cochlear hair cells necessary for hearing. In regard to central auditory processing at the level of the auditory midbrain, aquaporin gene expression changes may affect neurotransmitter cycling involving supporting cells, thus impairing complex sound neural processing with age.

  11. Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function.

    Science.gov (United States)

    Egawa, Junji; Pearn, Matthew L; Lemkuil, Brian P; Patel, Piyush M; Head, Brian P

    2016-08-15

    A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes.

  12. Synergistic effects of free radical scavengers and cochlear vasodilators: a new otoprotective strategy for age-related hearing loss

    Science.gov (United States)

    Alvarado, Juan Carlos; Fuentes-Santamaría, Verónica; Melgar-Rojas, Pedro; Valero, María Llanos; Gabaldón-Ull, María Cruz; Miller, Josef M.; Juiz, José M.

    2015-01-01

    The growing increase in age-related hearing loss (ARHL), with its dramatic reduction in quality of life and significant increase in health care costs, is a catalyst to develop new therapeutic strategies to prevent or reduce this aging-associated condition. In this regard, there is extensive evidence that excessive free radical formation along with diminished cochlear blood flow are essential factors involved in mechanisms of other stress-related hearing loss, such as that associated with noise or ototoxic drug exposure. The emerging view is that both play key roles in ARHL pathogenesis. Therapeutic targeting of excessive free radical formation and cochlear blood flow regulation may be a useful strategy to prevent onset of ARHL. Supporting this idea, micronutrient-based therapies, in particular those combining antioxidants and vasodilators like magnesium (Mg2+), have proven effective in reducing the impact of noise and ototoxic drugs in the inner ear, therefore improving auditory function. In this review, the synergistic effects of combinations of antioxidant free radicals scavengers and cochlear vasodilators will be discussed as a feasible therapeutic approach for the treatment of ARHL. PMID:26029103

  13. Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

    Science.gov (United States)

    Dulas, Michael R; Duarte, Audrey

    2016-05-15

    Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference.

  14. Glycinergic synaptic transmission in the cochlear nucleus of mice with normal hearing and age-related hearing loss.

    Science.gov (United States)

    Xie, Ruili; Manis, Paul B

    2013-10-01

    The principal inhibitory neurotransmitter in the mammalian cochlear nucleus (CN) is glycine. During age-related hearing loss (AHL), glycinergic inhibition becomes weaker in CN. However, it is unclear what aspects of glycinergic transmission are responsible for weaker inhibition with AHL. We examined glycinergic transmission onto bushy cells of the anteroventral CN in normal-hearing CBA/CaJ mice and in DBA/2J mice, a strain that exhibits an early onset AHL. Glycinergic synaptic transmission was examined in brain slices of mice at 10-15 postnatal days old, 20-35 days old, and at 6-7 mo old. Spontaneous inhibitory postsynaptic current (sIPSC) event frequency and amplitude were the same among all three ages in both strains of mice. However, the amplitudes of IPSCs evoked (eIPSC) from stimulating the dorsal CN were smaller, and the failure rate was higher, with increasing age due to decreased quantal content in both mouse strains, independent of hearing status. The coefficient of variation of the eIPSC amplitude also increased with age. The decay time constant (τ) of sIPSCs and eIPSCs were constant in CBA/CaJ mice at all ages, but were significantly slower in DBA/2J mice at postnatal days 20-35, following the onset of AHL, and not at earlier or later ages. Our results suggest that glycinergic inhibition at the synapses onto bushy cells becomes weaker and less reliable with age through changes in release. However, the hearing loss in DBA/2J mice is accompanied by a transiently enhanced inhibition, which could disrupt the balance of excitation and inhibition.

  15. Treatment of Age-Related Hearing Loss in Dogs with the Vibrant Soundbridge Middle Ear Implant : Short-Term Results in 3 Dogs

    NARCIS (Netherlands)

    Ter Haar, G.; Mulder, J. J.; Venker-van Haagen, A. J.; van Sluijs, F. J.; Snik, A. F.; Smoorenburg, G. F.

    2010-01-01

    Background Age-related hearing loss (ARHL), or presbycusis, is the most common form of acquired hearing loss in dogs. Middle ear implants have been used successfully in people with ARHL who cannot benefit from conventional hearing aids. Hypothesis Audibility improves in dogs with ARHL after implanta

  16. Treatment of age-related hearing loss in dogs with the vibrant soundbridge middle ear implant: short-term results in 3 dogs.

    NARCIS (Netherlands)

    Haar, G. Ter; Mulder, J.J.S.; Venker-van Haagen, A.J.; Sluijs, F.J. van; Snik, A.F.M.; Smoorenburg, G.F.

    2010-01-01

    BACKGROUND: Age-related hearing loss (ARHL), or presbycusis, is the most common form of acquired hearing loss in dogs. Middle ear implants have been used successfully in people with ARHL who cannot benefit from conventional hearing aids. HYPOTHESIS: Audibility improves in dogs with ARHL after implan

  17. Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

    Science.gov (United States)

    Guez, Jonathan; Naveh-Benjamin, Moshe

    2016-09-01

    Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.

  18. Understanding Memory Loss | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Memory & Forgetfulness Understanding Memory Loss Past Issues / Summer 2013 Table of Contents ... weeks at a time. Some Treatable Causes of Memory Loss As we age, our bodies change, including ...

  19. A high-fat diet delays age-related hearing loss progression in C57BL/6J mice.

    Directory of Open Access Journals (Sweden)

    Takeshi Fujita

    Full Text Available Age-related hearing loss (AHL, or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD.Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup. Nine CBA/N-slc mice were also used as a 12-month control (n = 5 or 12-month HFD (n = 4 group. The mice were fed a HFD or normal (control diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs. Spiral ganglion cells (SGCs were also counted.The elevation of ABR thresholds (at 4 and 32 kHz at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups.The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice.

  20. Age-related hearing loss in dogs : Diagnosis with Brainstem-Evoked Response Audiometry and Treatment with Vibrant Soundbridge Middle Ear Implant.

    NARCIS (Netherlands)

    ter Haar, G.

    2009-01-01

    Age-related hearing loss (ARHL) is the most common cause of acquired hearing impairment in dogs. Diagnosis requires objective electrophysiological tests (brainstem evoked response audiometry [BERA]) evaluating the entire audible frequency range in dogs. In our laboratory a method was developed to de

  1. The contribution of GJB2 (Connexin 26) 35delG to age-related hearing impairment and noise-induced hearing loss.

    NARCIS (Netherlands)

    Eyken, E. van; Laer, L. van; Fransen, E.; Topsakal, V.; Hendrickx, J.J.; Demeester, K.; Heyning, P. van de; Maki-Torkko, E.; Hannula, S.; Sorri, M.; Jensen, M.; Parving, A.; Bille, M.; Baur, M.; Pfister, M.; Bonaconsa, A.; Mazzoli, M.; Orzan, E.; Espeso, A.; Stephens, D.; Verbruggen, K.; Huyghe, J.; Dhooge, I.J.; Huygen, P.L.M.; Kremer, H.; Cremers, C.W.R.J.; Kunst, S.J.W.; Manninen, M.; Pyykko, I.; Rajkowska, E.; Pawelczyk, M.; Sliwinska-Kowalska, M.; Steffens, M.; Wienker, T.F.; Camp, G. van

    2007-01-01

    HYPOTHESIS: The common GJB2 (Connexin 26) 35delG mutation might contribute to the development of age-related hearing impairment (ARHI) and noise-induced hearing loss (NIHL). BACKGROUND: GJB2, a gene encoding a gap junction protein expressed in the inner ear, has been suggested to be involved in the

  2. Severity and pattern of bone mineral loss in endocrine causes of osteoporosis as compared to age-related bone mineral loss

    Directory of Open Access Journals (Sweden)

    D Dutta

    2016-01-01

    Full Text Available Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD loss in endocrinopathies [Graves′ disease (GD, type 1 diabetes mellitus (T1DM, hypogonadotrophic hypogonadism (HypoH, hypergonadotropic hypogonadism (HyperH, hypopituitarism, primary hyperparathyroidism (PHPT] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO, andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126 were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%, HyperH (85%, and HypoH (79.59% compared to age-related BMD loss (60.02%; P < 0.001. The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%, HyperH (85%, and HypoH (59.26% compared to PMO (49.34%; P < 0.001. Z score at LS, TF, NOF, and greater trochanter (GT was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67% and HypoH (54.55% compared to andropause (45.45%; P = 0.001. Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting.

  3. Untreated Sleep-Disordered Breathing: Links to Aging-Related Decline in Sleep-Dependent Memory Consolidation

    OpenAIRE

    Ina Djonlagic; Mengshuang Guo; Paul Matteis; Andrea Carusona; Robert Stickgold; Atul Malhotra

    2014-01-01

    Background: Increasing age is associated with a decline in cognition and motor skills, while at the same time exacerbating one's risk of developing obstructive sleep apnea (OSA). OSA-related cognitive deficits are highly prevalent and can affect various memory systems including overnight memory consolidation on a motor sequence task. Thus, the aim of our study was to examine the effect of aging on sleep-dependent motor memory consolidation in patients with and without OSA. Methods: We studied...

  4. Age-related alterations of brain network underlying the retrieval of emotional autobiographical memories: An fMRI study using independent component analysis

    Directory of Open Access Journals (Sweden)

    Ruiyang eGe

    2014-08-01

    Full Text Available Normal aging has been shown to modulate the neural underpinnings of autobiographical memory and emotion processing. Moreover, previous researches have suggested that aging produces a positivity effect in autobiographical memory. Although a few imaging studies have investigated the neural mechanism of the positivity effect, the neural substrates underlying the positivity effect in emotional autobiographical memory is unclear. To understand the age-related neural changes in emotional autobiographical memory that underlie the positivity effect, the present functional magnetic resonance imaging (fMRI study used the independent component analysis (ICA method to compare brain networks in younger and older adults as they retrieved positive and negative autobiographical events. Compared to their younger counterparts, older adults reported relatively higher positive feelings when retrieving emotional autobiographical events. Imaging data indicated an age-related reversal within the ventromedial prefrontal/anterior cingulate cortex (VMPFC/ACC and the left amygdala of the brain networks that were engaged in the retrieval of autobiographical events with different valence. The retrieval of negative events compared to positive events induced stronger activity in the VMPFC/ACC and weaker activity in the amygdala for the older adults, whereas the younger adults showed a reversed pattern. Moreover, activity in the VMPFC/ACC within the task-related networks showed a negative correlation with the emotional valence intensity. These results may suggest that the positivity effect in older adults’ autobiographical memories is potentially due to age-related changes in controlled emotional processing implemented by the VMPFC/ACC-amygdala circuit.

  5. Self-perceived memory impairment and cognitive performance in an elderly independent population with age-related white matter changes

    DEFF Research Database (Denmark)

    Miranda, B.; Madureira, S.; Verdelho, A.

    2008-01-01

    on global functioning. WMC severity was rated using the Fazekas scale. Medial temporal lobe atrophy (MTA) was scored visually and mean values were calculated. The neuropsychological battery consisted of the Mini-Mental State Examination, a modified version of the VADAS-Cog, Trail making and Stroop tests....... A question about self-perceived memory impairment was used as a measure for presence of memory complaints. Cognitive performance was analysed test-by-test and in three main domains: memory, executive functions and speed/motor control. The Geriatric Depression Scale (GDS) was used as a measure of depressive...... symptoms. RESULTS: Six hundred and thirty-eight subjects were included in this study. No association was found between memory complaints and the severity of WMC. Subjects with memory complaints (n = 399) had a higher GDS score [t((637)) = -7.15; ptests...

  6. Age-related hearing loss in dogs : Diagnosis with Brainstem-Evoked Response Audiometry and Treatment with Vibrant Soundbridge Middle Ear Implant.

    OpenAIRE

    ter Haar, G.

    2009-01-01

    Age-related hearing loss (ARHL) is the most common cause of acquired hearing impairment in dogs. Diagnosis requires objective electrophysiological tests (brainstem evoked response audiometry [BERA]) evaluating the entire audible frequency range in dogs. In our laboratory a method was developed to deliver tone bursts ranging in frequency from 1 - 32 kHz for frequency-specific assessment of the cochlea in dogs. Brainstem auditory evoked responses to a click (CS) and to 1, 2, 4, 8, 12, 16, 24, a...

  7. Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function.

    Science.gov (United States)

    Shindyapina, Anastasia V; Mkrtchyan, Garik V; Gneteeva, Tatiana; Buiucli, Sveatoslav; Tancowny, B; Kulka, M; Aliper, Alexander; Zhavoronkov, Alexander

    2014-04-01

    Age-related metastatic mineralization of soft tissues has been considered a passive and spontaneous process. Recent data have demonstrated that calcium salt deposition in soft tissues could be a highly regulated process. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Different mechanisms underlying calcium apatite accumulation are explored with these age-related disorders. In the case of atherosclerotic plaques, oxy-lipids trigger release of the pro-inflammatory cytokines and inflammation that activate calcification processes in aorta intimae. In CKD patients, renal failure alters the balance between calcium and phosphate levels usually regulated by fibroblast growth factor-23 (FGF23), Klotho, and vitamin D, and vascular smooth muscle cells (VSMCs) begin to explore an osteoblastosteoblast-like phenotype. Calcification could affect extracellular matrix along with VSMCs. Collagen is a major component of extracellular matrix and its modifications accumulate with age. The formation of cross-links between collagen fibers is regulated by the action of lysine hydroxylases and lysyl oxidase and could occur spontaneously. Oxidation-induced advanced glycation end products (AGEs) are a major type of spontaneous cross-links that accelerate with age and may result in tissue stiffness, problems with recycling, and potential accumulation of calcium apatite. Applying strategies for clearing the AGEs proposed by de Grey may be more difficult in the highly mineralized extracellular matrix. We performed bioinformatic analysis of the molecular pathways underlying calcification in atherosclerotic and CKD patients, signaling pathways of collagen cross-links formation, and bone mineralization, and we propose new potential targets and review drugs for calcification treatment.

  8. Computer-Based Cognitive Programs for Improvement of Memory, Processing Speed and Executive Function during Age-Related Cognitive Decline: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yan-kun Shao

    Full Text Available Several studies have assessed the effects of computer-based cognitive programs (CCP in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults.Six electronic databases (through October 2014 were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD and 95% confidence intervals (CI of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index.Twelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001 and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007 but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27. Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01.CCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings.

  9. The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    Science.gov (United States)

    Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

  10. Nigrostriatal rAAV-mediated GDNF Overexpression Induces Robust Weight Loss in a Rat Model of Age-related Obesity

    OpenAIRE

    Manfredsson, Fredric P; Tumer, Nihal; Erdos, Benedek; Landa, Tessa; Broxson, Christopher S; Sullivan, Layla F; Rising, Aaron C; Foust, Kevin D.; Zhang, Yi; Muzyczka, Nicholas; Gorbatyuk, Oleg S.; Scarpace, Philip J.; Mandel, Ronald J.

    2009-01-01

    Intraventricular administration of glial cell line–derived neurotrophic factor (GDNF) in primate and humans to study Parkinson's disease (PD) has revealed the potential for GDNF to induce weight loss. Our previous data indicate that bilateral continuous hypothalamic GDNF overexpression via recombinant adeno-associated virus (rAAV) results in significant failure to gain weight in young rats and weight loss in aged rats. Based on these previous results, we hypothesized that because the nigrostr...

  11. Age-related changes in neural activity during source memory encoding in young, middle-aged and elderly adults.

    Science.gov (United States)

    Cansino, Selene; Trejo-Morales, Patricia; Hernández-Ramos, Evelia

    2010-07-01

    Source memory, the ability to remember contextual information present at the moment an event occurs, declines gradually during normal aging. The present study addressed whether source memory decline is related to changes in neural activity during encoding across age. Event-related potentials (ERPs) were recorded in three groups of 14 subjects each: young (21-26 years), middle-aged (50-55 years) and older adults (70-77 years). ERPs were recorded while the subjects performed a natural/artificial judgment on images of common objects that were presented randomly in one of the quadrants of the screen (encoding phase). At retrieval, old images mixed with new ones were presented at the center of the screen and the subjects judged whether each image was new or old and, if old, were asked to indicate at which position of the screen the image was presented in the encoding session. The neurophysiological activity recorded during encoding was segregated for the study items according to whether their context was correctly retrieved or not, so as to search for subsequent memory effects (SME). These effects, which consisted of larger amplitude for items subsequently attracting a correct source judgment than an incorrect one, were observed in the three groups, but their onset was delayed across the age groups. The amplitude of the SME was similar across age groups at the frontal and central electrode sites, but was manifested more at the posterior sites in middle-aged and older adults, suggesting that source memory decline may be related to less efficient encoding mechanisms.

  12. Age-related ranges of memory, activation, and cytotoxic markers on CD4 and CD8 cells in children.

    Science.gov (United States)

    Aldhous, M C; Raab, G M; Doherty, K V; Mok, J Y; Bird, A G; Froebel, K S

    1994-09-01

    The expression of markers defining functional subpopulations on the surface of CD4 and CD8 cells changes with disease. To monitor these changes in children, it is important to establish the age-related normal changes in marker expression due to maturation of the immune system. We have studied the expression of several functionally important molecules on both CD4 and CD8 cells in 168 children (aged 0-122 months) using monoclonal antibodies and flow cytometry. Our results show that the percentage of CD4 cells decreases with age, while the CD8 percentage increases, resulting in a decrease in the CD4/CD8 ratio. The expression of CD45RO and CD29 increases with age, while CD45RA expression decreases, both on CD4 and CD8 cells. The expression of HLA-DR on both CD4 and CD8 cells, and of CD11a and CD57 on CD8 cells, is less clearly age dependent. The relationships between the marker percentages and age were not straightforward; the standard deviations and the skewness, as well as their mean values, varied as a function of age. The changes were modeled for each marker and age-specific centiles are presented.

  13. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    Science.gov (United States)

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects.

  14. Are Age-Related Differences Between Young and Older Adults in an Affective Working Memory Test Sensitive to the Music Effects?

    Directory of Open Access Journals (Sweden)

    Erika eBorella

    2014-11-01

    Full Text Available There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words, are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni, which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task were analyzed.Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni. However, as in previous studies, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences, in terms of accuracy in the processing phase of the Operation Span task, were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music.Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are less sensitive to music effects.

  15. Age-Related Benefits of Digital Noise Reduction for Short-Term Word Learning in Children with Hearing Loss

    Science.gov (United States)

    Pittman, Andrea

    2011-01-01

    Purpose: To determine the rate of word learning for children with hearing loss (HL) in quiet and in noise compared to normal-hearing (NH) peers. The effects of digital noise reduction (DNR) were examined for children with HL. Method: Forty-one children with NH and 26 children with HL were grouped by age (8-9 years and 11-12 years). The children…

  16. 利用基因芯片检测大鼠衰老相关的记忆障碍的调控基因%Identification of genes associated with age-related memory impairment in rats

    Institute of Scientific and Technical Information of China (English)

    张双; 王琳; 董素珍

    2011-01-01

    A large body of evidence indicates that memory impairment is associated with normal aging.Interestingly,some older individuals do not show any memory loss.To understand the molecular mechanisms of the age-related memory disorder,gene expression profiles of hippocampus and entorhinal cortex from 24-month-old memory-impaired and memory-unimpaired rats that were divided based on their performance in Morris water maze were examined using high-density DNA microarrays.The results demonstrated that 47 genes in the hippocampus and 37 genes in the entorhinal cortex showed dynamic changes in their expression levels.Surprisingly,the overall patterns of gene expression changes in these two brain regions were significantly different.Nevertheless,a number of key genes involved in structure organization,neurotransmission,signaling transduction,transcription,immunity and oxidative signaling were differently expressed in both brain regions.These genes and signal pathways may play essential roles in the regulation of memory.Our results provided important information for understanding the molecular mechanism of age-related memory impairment.%许多证据表明,正常衰老过程伴随着记忆力的衰退.但有些动物却不表现出这种年龄相关的记忆障碍.为了检测其中的分子机制,将24个月的老年大鼠按在水迷宫中的行为表现分成记忆损伤组和记忆未损伤组,分别取海马和内嗅皮层进行基因芯片检测.结果显示,在海马和内嗅皮层中分别有47和37个基因的表达发生了显著变化.但两个脑区的基因表达变化模式却有明显的不同.对差异表达的基因进行功能分析,主要是与结构组织、突触传递、信号转导、转录及免疫和氧化信号相关的基因.这些基因和信号通路可能在记忆的调控过程中起重要作用.该结果为进一步揭示衰老相关的记忆衰退过程的分子机制提供了重要的信息.

  17. miR-29b overexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1α signaling: Implications for age-related hearing loss

    Science.gov (United States)

    Xue, Tao; Wei, Li; Zha, Ding-Jun; Qiu, Jian-Hua; Chen, Fu-Quan; Qiao, Li; Qiu, Yang

    2016-01-01

    It has been reported that the degeneration of cochlear hair cells is the typical cause of presbycusis (or age-related hearing loss). However, the molecular mechanisms that mediate cochlear hair cell apoptosis are not yet fully understood and there is no effective treatment for this disorder. MicroRNAs (miRNAs or miRs) have been increasingly shown to be associated with age-related diseases and are emerging as promising therapeutic targets. In this study, we investigated whether miR-29b is involved in the degeneration of cochlear hair cells. To examine our hypothesis, nuclear staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) were used to quantify the hair cell counts. RT-qPCR and western blot analysis were used to examine miR-29b/sirtuin 1 (SIRT1)/proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in cochlear hair cells. We found that there was a significant degeneration of cochlear hair cells and a higher expression of miR-29b in aged C57BL/6 mice compared with young mice. There was also an age-related decrease in the expression of SIRT1 and PGC-1α. In the inner ear cell line, HEI-OC1, miR-29b overexpression (by transfection with miR-29b mimic) inhibited SIRT1 and PGC-1α expression, leading to an increase in mitochondrial dysfunction and apoptosis. Moreover, the inhibition of miR-29b (by transfection with miR-29b inhibitor) increased SIRT1 and PGC-1α expression, while it decreased apoptosis. Taken together, our findings support a link between age-related cochlear hair cell apoptosis and miR-29b/SIRT1/PGC-1α signaling, which may present an attractive pharmacological target for the development of novel drugs for the treatment of age-related hearing loss. PMID:27635430

  18. Stability against backward balance loss: Age-related modifications following slip-like perturbations of multiple amplitudes.

    Science.gov (United States)

    Martelli, Dario; Aprigliano, Federica; Tropea, Peppino; Pasquini, Guido; Micera, Silvestro; Monaco, Vito

    2017-03-01

    Falls are one of the most serious problems in the elderly. Although previous studies clearly link the increased risk of falls with ageing, the mechanisms responsible for the modifications of reactive motor behaviours in response to external perturbations are not yet fully understood. This study investigated how the stability against backward balance loss is affected by aging and intensity of perturbations. The Margin of Stability (MoS) was estimated while eight young and eight elderly adults managed three slip-like perturbations of different intensities while walking at the same normalized speed. A compensatory step was necessary to regain stability. The forward swing phase of the trailing leg was rapidly interrupted and reversed in direction. Results have shown that ageing significantly affects the time required to select the most appropriate biomechanical response: even if the characteristic of the backward step was similar between groups, elderly subjects took more time to reverse the movement of their swinging limb, thus achieving a less efficient action to counteract the backward balance loss (lower MoS both during and at the end of the early compensatory reaction). In addition, young and elderly subjects scaled their reactions with respect to the perturbations intensity in a similar way by increasing the length of their backward step, thus revealing a context-dependent tuning of the biomechanical response that was not affected by aging. These behavioural features can be helpful in identifying the causes of increased fall risk among the elderly in order to define more suited intervention in fall prevention programs.

  19. Age-related changes in frequency of mind-wandering and task-related interferences during memory encoding and their impact on retrieval.

    Science.gov (United States)

    Maillet, David; Rajah, M Natasha

    2013-01-01

    During the performance of cognitive tasks such as memory encoding, attention can become decoupled from the external environment and instead focused on internal thoughts related to the appraisal of the current task (task-related interferences; TRI), or personal thoughts unrelated to the task at hand (mind-wandering; MW). However, the association between the frequency of these thoughts experienced at encoding and retrieval accuracy in young and older adults remains poorly understood. In this study young and older adults encoded lists of words using one of two encoding tasks: judging whether words are man-made/natural (objective task), or whether they are pleasant/neutral (subjective task). We measured the frequency of TRI and MW at encoding, and related them to retrieval accuracy in both age groups. We found that encoding task influenced the type of internal thoughts experienced by young, but not older, adults: young exhibited greater MW in the subjective vs the objective task, and greater TRI in the objective vs subjective encoding task. Second, across both tasks we found marked age-related decreases in both MW and TRI at encoding, and frequency of these thoughts negatively impacted memory retrieval in young adults only. We discuss these findings in relation to current theories of ageing, attention and memory.

  20. Age-related changes in electrophysiological and neuropsychological indices of working memory, attention control, and fluid intelligence

    Directory of Open Access Journals (Sweden)

    Carrie Brumback Peltz

    2011-08-01

    Full Text Available Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span task (OSPAN, a measure of attention control is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally-distributed P300 (or P3b. Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively. To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction-time task. For both age groups (a participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life.

  1. A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice

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    Raquel Riquelme

    2010-06-01

    Full Text Available Insulin-like growth factor-I (IGF-I belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to

  2. A Comparative Study of Age-Related Hearing Loss in Wild Type and Insulin-Like Growth Factor I Deficient Mice

    Science.gov (United States)

    Riquelme, Raquel; Cediel, Rafael; Contreras, Julio; Lourdes, Rodriguez-de la Rosa; Murillo-Cuesta, Silvia; Hernandez-Sanchez, Catalina; Zubeldia, Jose M.; Cerdan, Sebastian; Varela-Nieto, Isabel

    2010-01-01

    Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or

  3. Age-Related Macular Degeneration

    Science.gov (United States)

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  4. Age-related changes in auditory and cognitive abilities in elderly persons with hearing aids fitted at the initial stages of hearing loss

    Directory of Open Access Journals (Sweden)

    C. Obuchi

    2011-03-01

    Full Text Available In this study, we investigated the relation between the use of hearing aids at the initial stages of hearing loss and age-related changes in the auditory and cognitive abilities of elderly persons. 12 healthy elderly persons participated in an annual auditory and cognitive longitudinal examination for three years. According to their hearing level, they were divided into 3 subgroups - the normal hearing group, the hearing loss without hearing aids group, and the hearing loss with hearing aids group. All the subjects underwent 4 tests: pure-tone audiometry, syllable intelligibility test, dichotic listening test (DLT, and Wechsler Adult Intelligence Scale-Revised (WAIS-R Short Forms. Comparison between the 3 groups revealed that the hearing loss without hearing aids group showed the lowest scores for the performance tasks, in contrast to the hearing level and intelligibility results. The other groups showed no significant difference in the WAIS-R subtests. This result indicates that prescription of a hearing aid during the early stages of hearing loss is related to the retention of cognitive abilities in such elderly people. However, there were no statistical significant correlations between the auditory and cognitive tasks.

  5. 1,2-Dilinoleoyl-sn-glycero-3-phosphoethanolamine ameliorates age-related spatial memory deterioration by preventing neuronal cell death

    Directory of Open Access Journals (Sweden)

    Yaguchi Takahiro

    2010-09-01

    Full Text Available Abstract Background Accumulating evidence has pointed that a variety of lipids could exert their beneficial actions against dementia including Alzheimer disease and age-related cognitive decline via diverse signaling pathways. Endoplasmic reticulum (ER stress-induced neuronal apoptosis, on the other hand, is a critical factor for pathogenesis of neurodegenerative diseases such as Alzheimer disease and Parkinson disease, senile dementia, and ischemic neuronal damage. The present study examined the effects of 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPhtEtn, a phospholipid, on ER stress-induced neuronal death and age-related cognitive disorders. Methods PC-12 cell viability was assayed before and after treatment with amyloid-β1-40 peptide or thapsigargin in the presence and absence of DLPhtEtn. A series of behavioral tests were performed for senescence-accelerated mouse-prone 8 (SAMP8 mice after 7-month oral administration with polyethylene glycol (PEG or DLPhtEtn and then, the number of hippocampal neurons was counted. Results Amyloid-β1-40 peptide or thapsigargin is capable of causing ER stress-induced apoptosis. DLPhtEtn (30 μM significantly inhibited PC-12 cell death induced by amyloid-β1-40 peptide or thapsigargin. In the water maze test, oral administration with DLPhtEtn (1 mg/kg for 7 months (three times a week significantly shortened the prolonged retention latency for SAMP8 mice. In contrast, DLPhtEtn had no effect on the acquisition and retention latencies in both the open field test and the passive avoidance test for SAMP8 mice. Oral administration with DLPhtEtn (1 mg/kg for 7 months prevented a decrease in the number of hippocampal neurons for SAMP8 mice. Conclusion The results of the present study show that DLPhtEtn ameliorates age-related spatial memory decline without affecting motor activities or fear memory, possibly by protecting hippocampal neuronal death. DLPhtEtn, thus, might exert its beneficial action against

  6. The quality of life impact of peripheral versus central vision loss with a focus on glaucoma versus age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Keith Evans

    2009-07-01

    Full Text Available Keith Evans1, Simon K Law2, John Walt3, Patricia Buchholz4, Jan Hansen31Global Health Outcomes, Wolters Kluwer Health, Chester, United Kingdom; 2Jules Stein Eye Institute, Los Angeles, CA, USA; 3Global Health Outcomes Strategy and Research, Allergan Inc., Irvine, CA, USA; 4Health Economics, Pricing, and Reimbursement, Allergan GmbH, Ettlingen, GermanyPurpose: It is well accepted that conditions that cause central vision loss (CVL have a negative impact on functional ability and quality of life (QoL, but the impact of diseases that cause peripheral vision loss (PVL is less well understood. Focusing on glaucoma and age-related macular degeneration (ARMD, the effects of CVL and PVL on QoL were compared. Methods: A systematic literature review of publications reporting QoL in patients with CVL or PVL identified 87 publications using four generic (Short-Form Health Survey-36 and -12, EuroQoL EQ-5D and Sickness Impact Profile and five vision-specific (National Eye Institute Visual Function Questionnaire-51, -39, and -25, Impact of Vision Impairment and Visual Function-14 QoL instruments; 33 and 15 publications reported QoL in ARMD and glaucoma, respectively.Results: QoL was impaired to a similar extent by diseases associated with PVL and CVL, but different domains were affected. In contrast to ARMD, mental aspects appeared to be affected more than physical aspects in patients with glaucoma.Conclusions: The differential impact upon QoL might be a function of the pathology of the diseases, for example potential for blindness and better ability to perform physical tasks due to retention of central vision may explain these observations in glaucoma.Keywords: vision loss, quality of life, glaucoma, age-related macular degeneration, diabetic macular edema, cataracts

  7. Compromised potassium recycling in the cochlea contributes to conservation of endocochlear potential in a mouse model of age-related hearing loss.

    Science.gov (United States)

    Yang, Haidi; Xiong, Hao; Huang, Qiuhong; Pang, Jiaqi; Zheng, Xuqing; Chen, Lian; Yu, Rongjun; Zheng, Yiqing

    2013-10-25

    The C57BL/6 strain is considered an excellent model to study age-related hearing loss (AHL). Aging C57BL/6 mice are characterized by profound hearing loss but conservation of the endocochlear potential (EP). Here we show 12-month-old C57BL/6 mice display a notable hearing loss at 4, 8, 16 and 32kHz while the EP is maintained at normal level. Morphological examination shows significant outer hair cells loss in the cochlear basal turn and atrophy of the stria vascularis (SV). Fluorescence immunohistochemical studies reveal that potassium channel KCNJ10 and KCNQ1 expression dramatically decreased in the SV. Concomitant with this, mRNA levels of KCNJ10 and KCNQ1 are also reduced. In addition, three other potassium transporters, including α1-Na,K-ATPase, α2-Na,K-ATPase and NKCC1, reduce their expression at mRNA levels as well. These observations suggest that conservation of the EP in aging C57BL/6 mice is attributable to the SV generating a new balance for potassium influx and efflux at a relatively lower level.

  8. Age-Related Hearing Loss

    Science.gov (United States)

    ... eardrum. The eardrum vibrates from the incoming sound waves and sends these vibrations to three tiny bones in the middle ear. ... on which key hearing structures sit. Once the vibrations cause the fluid inside the cochlea to ripple, a traveling wave forms along the basilar membrane. Hair cells—sensory ...

  9. Experience and information loss in auditory and visual memory.

    Science.gov (United States)

    Gloede, Michele E; Paulauskas, Emily E; Gregg, Melissa K

    2017-07-01

    Recent studies show that recognition memory for sounds is inferior to memory for pictures. Four experiments were conducted to examine the nature of auditory and visual memory. Experiments 1-3 were conducted to evaluate the role of experience in auditory and visual memory. Participants received a study phase with pictures/sounds, followed by a recognition memory test. Participants then completed auditory training with each of the sounds, followed by a second memory test. Despite auditory training in Experiments 1 and 2, visual memory was superior to auditory memory. In Experiment 3, we found that it is possible to improve auditory memory, but only after 3 days of specific auditory training and 3 days of visual memory decay. We examined the time course of information loss in auditory and visual memory in Experiment 4 and found a trade-off between visual and auditory recognition memory: Visual memory appears to have a larger capacity, while auditory memory is more enduring. Our results indicate that visual and auditory memory are inherently different memory systems and that differences in visual and auditory recognition memory performance may be due to the different amounts of experience with visual and auditory information, as well as structurally different neural circuitry specialized for information retention.

  10. Study of age-related changes in emotional memory%年龄相关性情绪记忆的研究

    Institute of Scientific and Technical Information of China (English)

    唐向阳; 袁良津; 汪凯

    2015-01-01

    Objective To identify age-related changes in emotional memory.Methods A neuropsychological battery was set to measure the education-matched 48 younger, 48 middle-aged and 48 normally aging adults who were given picture tasks.Results Compared with the younger [positive (67.02 ±9.70)%,neutral (60.83 ±9.18)%, negative(75.38 ±12.80)%] and middle-aged controls [positive (68.25 ±10.89),neutral (61.63 ±7.46)%, negative (72.19 ±11.34)%], the differences of the affective images recognition accuracy in the elderly [positive (61.10 ±10.06)%, neutral (49.77 ±8.35)%, negative (55.65 ±11.17)%] were statistically significant (F=6.70,F=30.17,F=38.72,P<0.05-0.01), older adults remembering positive image better than negative image (F=15.67,P<0.05).However, there was no significant difference in their rating of valence of the images. Conclusion Emotional memory is impaired in the healthy elderly people, and indicates that age-related changes in emotional memory indicates may have different neuromechanisms.%目的 探讨年龄相关性情绪记忆的情况. 方法 建立情绪记忆的神经心理学测验方法,测试教育程度相匹配的48名健康老年人、48名健康中年人和48名健康青年人的情绪记忆.结果 与青年组[正性(67.02 ±9.70)%、中性(60.83 ±9.18)%、负性(75.38 ±12.80)%]和中年组[正性(68.25 ±10.89)%、中性(61.63 ±7.46)%、负性(72.19 ±11.34)%]相比,老年组[正性(61.10 ±10.06)%、中性(49.77 ±8.35)%、负性(55.65 ±11.17)%]对情绪图片再认正确率差异均有统计学意义( F=6.70、F=30.17、F=38.72,P<0.05~0.01),且老年组对正性图片记忆好于负性图片(F=15.65,P<0.05);而对情绪图片效价评分差异无统计学意义. 结论 健康老年人存在情绪记忆的改变,推测年龄相关性情绪记忆的改变可能有不同的神经机制.

  11. Possible age-related hearing loss (presbycusis) and corresponding change in echolocation parameters in a stranded Indo-Pacific humpback dolphin.

    Science.gov (United States)

    Li, Songhai; Wang, Ding; Wang, Kexiong; Hoffmann-Kuhnt, Matthias; Fernando, Nimal; Taylor, Elizabeth A; Lin, Wenzhi; Chen, Jialin; Ng, Timothy

    2013-11-15

    The hearing and echolocation clicks of a stranded Indo-Pacific humpback dolphin (Sousa chinensis) in Zhuhai, China, were studied. This animal had been repeatedly observed in the wild before it was stranded and its age was estimated to be ~40 years. The animal's hearing was measured using a non-invasive auditory evoked potential (AEP) method. Echolocation clicks produced by the dolphin were recorded when the animal was freely swimming in a 7.5 m (width)×22 m (length)×4.8 m (structural depth) pool with a water depth of ~2.5 m. The hearing and echolocation clicks of the studied dolphin were compared with those of a conspecific younger individual, ~13 years of age. The results suggested that the cut-off frequency of the high-frequency hearing of the studied dolphin was ~30-40 kHz lower than that of the younger individual. The peak and centre frequencies of the clicks produced by the older dolphin were ~16 kHz lower than those of the clicks produced by the younger animal. Considering that the older dolphin was ~40 years old, its lower high-frequency hearing range with lower click peak and centre frequencies could probably be explained by age-related hearing loss (presbycusis).

  12. Auditory Brainstem Gap Responses Start to Decline in Middle Age Mice: A Novel Physiological Biomarker for Age-Related Hearing Loss

    Science.gov (United States)

    Williamson, Tanika T.; Zhu, Xiaoxia; Walton, Joseph P.; Frisina, Robert D.

    2014-01-01

    The CBA/CaJ mouse strain's auditory function is normal during the early phases of life and gradually declines over its lifespan, much like human age-related hearing loss (ARHL), but on a mouse life cycle “time frame”. This pattern of ARHL is relatively similar to that of most humans: difficult to clinically diagnose at its onset, and currently not treatable medically. To address the challenge of early diagnosis, CBA mice were used for the present study to analyze the beginning stages and functional onset biomarkers of ARHL. The results from Auditory Brainstem Response (ABR) audiogram and Gap-in-noise (GIN) ABR tests were compared for two groups of mice of different ages, young adult and middle age. ABR peak components from the middle age group displayed minor changes in audibility, but had a significantly higher prolonged peak latency and decreased peak amplitude in response to temporal gaps in comparison to the young adult group. The results for the younger subjects revealed gap thresholds and recovery rates that were comparable to previous studies of auditory neural gap coding. Our findings suggest that age-linked degeneration of the peripheral and brainstem auditory system is already beginning in middle age, allowing for the possibility of preventative biomedical or hearing protection measures to be implemented as a possibility for attenuating further damage to the auditory system due to ARHL. PMID:25307161

  13. Auditory brainstem gap responses start to decline in mice in middle age: a novel physiological biomarker for age-related hearing loss.

    Science.gov (United States)

    Williamson, Tanika T; Zhu, Xiaoxia; Walton, Joseph P; Frisina, Robert D

    2015-07-01

    The auditory function of the CBA/CaJ mouse strain is normal during the early phases of life and gradually declines over its lifespan, much like human age-related hearing loss (ARHL) but within the "time frame" of a mouse life cycle. This pattern of ARHL is similar to that of most humans: difficult to diagnose clinically at its onset and currently not treatable medically. To address the challenge of early diagnosis, we use CBA mice to analyze the initial stages and functional onset biomarkers of ARHL. The results from Auditory Brainstem Response (ABR) audiogram and Gap-in-noise (GIN) ABR tests were compared for two groups of mice of different ages, namely young adult and middle age. ABR peak components from the middle age group displayed minor changes in audibility but had a significantly higher prolonged peak latency and decreased peak amplitude in response to temporal gaps in comparison with the young adult group. The results for the younger subjects revealed gap thresholds and recovery rates that were comparable with previous studies of auditory neural gap coding. Our findings suggest that age-linked degeneration of the peripheral and brainstem auditory system begins in middle age, allowing for the possibility of preventative biomedical or hearing protection measures to be implemented in order to attenuate further damage to the auditory system attributable to ARHL.

  14. Auditory Memory deficit in Elderly People with Hearing Loss

    Directory of Open Access Journals (Sweden)

    Zahra Shahidipour

    2013-06-01

    Full Text Available Introduction: Hearing loss is one of the most common problems in elderly people. Functional side effects of hearing loss are various. Due to the fact that hearing loss is the common impairment in elderly people; the importance of its possible effects on auditory memory is undeniable. This study aims to focus on the hearing loss effects on auditory memory.   Materials and Methods: Dichotic Auditory Memory Test (DVMT was performed on 47 elderly people, aged 60 to 80; that were divided in two groups, the first group consisted of elderly people with hearing range of 24 normal and the second one consisted of 23 elderly people with bilateral symmetrical ranged from mild to moderate Sensorineural hearing loss in the high frequency due to aging in both genders.   Results: Significant difference was observed in DVMT between elderly people with normal hearing and those with hearing loss (P

  15. Content Analysis of Memory and Memory-Related Research Studies on Children with Hearing Loss

    Science.gov (United States)

    Dogan, Murat; Hasanoglu, Gülcihan

    2016-01-01

    Memory plays a profound role in explaining language development, academic learning, and learning disabilities. Even though there is a large body of research on language development, literacy skills, other academic skills, and intellectual characteristics of children with hearing loss, there is no holistic study on their memory processes.…

  16. Exercise May Help People Who Already Have Memory Loss

    Science.gov (United States)

    ... Videos & Tools Español You Are Here: Home → Latest Health News → Article URL of this page: https://medlineplus.gov/news/fullstory_161574.html Exercise May Help People Who Already Have Memory Loss But effects only lasted as long as activity continued, study ...

  17. Zooming in on the hippocampus in aging and age-related diseases

    NARCIS (Netherlands)

    Wisse, L.E.M.

    2014-01-01

    The hippocampal formation is a brain structure important for memory and emotion regulation. The hippocampal formation is susceptible to aging and age-related diseases, which is manifested as volume loss, visible on MRI scans. The hippocampal formation consists of several subfields with different cel

  18. Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

    Science.gov (United States)

    Bender, Andrew R.; Raz, Naftali

    2012-01-01

    Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…

  19. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to diff

  20. Medial prefrontal–hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to diff

  1. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  2. The quality of life impact of peripheral versus central vision loss with a focus on glaucoma versus age-related macular degeneration

    OpenAIRE

    Evans, Keith; Law, Simon; Walt, John; Buchholz, Patricia; Hansen,

    2009-01-01

    Keith Evans1, Simon K Law2, John Walt3, Patricia Buchholz4, Jan Hansen31Global Health Outcomes, Wolters Kluwer Health, Chester, United Kingdom; 2Jules Stein Eye Institute, Los Angeles, CA, USA; 3Global Health Outcomes Strategy and Research, Allergan Inc., Irvine, CA, USA; 4Health Economics, Pricing, and Reimbursement, Allergan GmbH, Ettlingen, GermanyPurpose: It is well accepted that conditions that cause central vision loss (CVL) have a negative impact on functional ability and quality of li...

  3. Age-related prefrontal over-recruitment in semantic memory retrieval: Evidence from successful face naming and the tip-of-the-tongue state.

    Science.gov (United States)

    Galdo-Alvarez, Santiago; Lindín, Mónica; Díaz, Fernando

    2009-09-01

    Studies that have attempted to determine the effects of aging on the brain neural sources of memory retrieval have reported two contrasting age effects: under-recruitment and over-recruitment of several prefrontal areas. However, the causes for these effects are still a matter of debate. In order to study the underlying factors that cause the effects, we compared brain activation in young and older adults, in a successful word retrieval condition, and a failed word retrieval condition: the tip-of-the-tongue state. For this, we used the event-related potentials technique and neural source estimation with low-resolution tomographies. The results showed that the older adults did not display under-recruitment in any brain area in comparison with the young adults. However, they displayed additional prefrontal activation that varied depending on the processing stage and the condition, which supports the hypothesis of selective over-recruitment in older adults.

  4. Physical activity as intervention for age-related loss of muscle mass and function: protocol for a randomised controlled trial (the LISA study)

    Science.gov (United States)

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde; Wimmelmann, Cathrine Lawaetz; Bieler, Theresa; Ziegler, Andreas Kraag; Gylling, Anne Theil; Dideriksen, Kasper Juel; Siebner, Hartwig Roman; Mortensen, Erik Lykke; Kjaer, Michael

    2016-01-01

    Introduction Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative. The primary aim of this randomised controlled trial is to compare the efficacy of two different 1 year strength training regimens on immediate and long-lasting improvements in muscle power in retirement-age individuals. Secondary aims are to evaluate the effect on muscle strength, muscle mass, physical and cognitive function, mental well-being, health-related quality of life and brain morphology. Methods and analysis The study includes 450 home-dwelling men and women (62–70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate intensity resistance training or (3) habitual physical activity (control). Changes in primary (leg extensor power) and secondary outcomes are analysed according to the intention to treat principle and per protocol at 1, 2, 4, 7 and 10 years. Ethics and dissemination The study is expected to generate new insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer-reviewed journals, in PhD theses and at public meetings. The study is approved by the Regional Ethical Committee (Capital Region, Copenhagen, Denmark, number H-3

  5. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    Science.gov (United States)

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice.

  6. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

    Science.gov (United States)

    Varela-López, Alfonso; Ochoa, Julio J.; Llamas-Elvira, José M.; López-Frías, Magdalena; Planells, Elena; Ramirez-Tortosa, MCarmen; Ramirez-Tortosa, Cesar L.; Giampieri, Francesca; Battino, Maurizio; Quiles, José L.

    2017-01-01

    During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals. PMID:28241421

  7. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

    Directory of Open Access Journals (Sweden)

    Alfonso Varela-López

    2017-02-01

    Full Text Available During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10, to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA-based diet for bone mineral density (BMD preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.

  8. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle.

    Science.gov (United States)

    Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P; Nye, Gareth A; Wells, Nicola; Giakoumaki, Ifigeneia I; Griffiths, Richard D; McArdle, Anne; Jackson, Malcolm J

    2016-11-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.-Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  9. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

    Science.gov (United States)

    Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

    2016-10-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories.

  10. The Pubmed Bibliometric Analysis of Trend in the Research on Age-related Hearing Loss%老年性聋相关研究热点Pubmed的文献计量学分析

    Institute of Scientific and Technical Information of China (English)

    郭敏; 韦焘; 纳玉萍; 江超武; 叶聪俊; 高竞逾; 杨丽珠; 纳靖; 阮标

    2015-01-01

    Objective This study aimed to define research status of age -related hearing loss ,and provide the basis and direction for future research .Methods We have retrieved all relevant literatures on age -related hearing loss from Pubmed ,and conduct an objective analysis of the existing literatures by Bibliometric analytics and co -word analysis method using co -occurrence bibliographic information mining system and SPSS22 .0 software for data analysis .Results There were a large number of articles and journals about presbycusis and age -related hearing loss .Many countries were involved in the research .Literatures and core authors were mainly from developed coun‐tries such as Europe and the United States .The quantity and quality of Chinese literatures were in a leading position in Asia .The researches focused on the common characteristics of patients ,the epidemiology ,characteristics of hear‐ing ,treatment and laboratory studies .There were some new research directions in recent 5 years ,such as factors as‐sociated with the younger ages before developing presbycusis ,standard design and use of questionnaires ,prevention and control .Conclusion Age-related hearing loss will continue to be a hot topic with growing focus on micro and macro development of multi -disciplinary cooperation .The penetration will be the trend for the future research while the prevention will become a new focus of research .%目的:了解老年性聋的研究现状,为进一步的研究提供依据和方向。方法检索Pubmed数据库中所有老年性聋相关文献,通过文献计量分析学和共词分析方法进行客观分析,使用书目信息共现挖掘系统和SPSS22.0软件进行数据分析。分析内容包括文献年代分布、期刊分布、作者分布、国家和语言分布、相关高频主题词和共词分布。结果老年性聋的研究文献数量逐年增多,期刊分布广,全球多国均参与研究,欧美等发达国家是文献数量和

  11. Hearing Loss Is Negatively Related to Episodic and Semantic Long-Term Memory but Not to Short-Term Memory

    Science.gov (United States)

    Ronnberg, Jerker; Danielsson, Henrik; Rudner, Mary; Arlinger, Stig; Sternang, Ola; Wahlin, Ake; Nilsson, Lars-Goran

    2011-01-01

    Purpose: To test the relationship between degree of hearing loss and different memory systems in hearing aid users. Method: Structural equation modeling (SEM) was used to study the relationship between auditory and visual acuity and different cognitive and memory functions in an age-hetereogenous subsample of 160 hearing aid users without…

  12. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  13. Factors affecting graded and ungraded memory loss following hippocampal lesions.

    Science.gov (United States)

    Winocur, Gordon; Moscovitch, Morris; Sekeres, Melanie J

    2013-11-01

    This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed.

  14. 14-year incidence, progression, and visual morbidity of age-related maculopathy

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Nielsen, Niels V; Vinding, Troels;

    2005-01-01

    To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss.......To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss....

  15. Longevity pathways and memory ageing

    Directory of Open Access Journals (Sweden)

    Ilias eGkikas

    2014-06-01

    Full Text Available The ageing process has been associated with numerous pathologies at the cellular, tissue, and organ level. Decline or loss of brain functions, including learning and memory, is one of the most devastating and feared aspects of ageing. Learning and memory are fundamental processes by which animals adjust to environmental changes, evaluate various sensory signals based on context and experience, and make decisions to generate adaptive behaviours. Age-related memory impairment is an important phenotype of brain ageing. Understanding the molecular mechanisms underlying age-related memory impairment is crucial for the development of therapeutic strategies that may eventually lead to the development of drugs to combat memory loss. Studies in invertebrate animal models have taught us much about the physiology of ageing and its effects on learning and memory. In this review we survey recent progress relevant to conserved molecular pathways implicated in both ageing and memory formation and consolidation.

  16. C57BL/6J小鼠听力损失与认知功能下降的相关性%Correlation between age-related hearing loss and impairment of cognition in C57BL/6J mice

    Institute of Scientific and Technical Information of China (English)

    于亚峰; 翟丰; 戴春富; 胡金家

    2011-01-01

    Objective To explore the correlation of age-related hearing loss and cognition impairment in C57BL/6J mice by observing hearing, cognitive function and synapses. Methods C57BL/6J and CBA/CaJ mice were divided into 3 groups. The hearing and cognitive functions of each animal was tested. And the ultrastructure of synapses was simultaneously observed for C57BL/6J mice. Results The 24-26-week-old C57BL/6J mice developed moderate hearing loss while the 42- 44-week-old C57BL/6J counterparts suffered profound hearing loss. Whereas excellent hearing was maintained in 3 groups of CBA/CaJ mice within 44 weeks. During cognitive test, the performance of 42 -44-week-old C57BL/6J mice was significantly worse than CBA/CaJ mice. During probe test, the number of platform crossing of 42 - 44-week-old C57BL/6J mice was smaller than that of CBA/CaJ mice(0.5 ± 0.6 vs 1.9 ± 1.6; P < 0.05 ). The 42 -44-week-old C57BL/6J mice had a wider synaptic cleft and a thinner postsynaptic density than the 24 -26-week-old C57 BL/6J counterparts [synaptic cleft: ( 19.4 ± 0.5 ) nm vs ( 1 1. 9 ± 0.7 ) nm; postsynaptic density:(15.2 ±0. 5) nm vs (27.8 ±2.0) nm; both P <0.05]. Furthermore, the degeneration of synapses in hippocampus CA3 area of C57BL/6J mice were clearly observed at 42 -44 weeks of age, but not seen in CBA/CaJ mice. Conclusion Age-related hearing loss might impact on the cognition impairment in C57 BL/6J mice.%目的 通过对老年性聋模型鼠C57BL/6J和对照组CBA/CaJ小鼠听力检测,认知行为检测以及海马CA3区突触超微结构的观察,探讨C57BL/6J小鼠年龄相关性听力损失与认知功能下降的关系。方法 将C57BL/6J小鼠根据听力随年龄的变化,按年龄分为3组:6~8周、24~26周、42~44周,每组10只。CBA/CaJ小鼠按同样的年龄也分为3组,每组9只。以TDT-Ⅲ型ABR测试仪检测听力,Morris水迷宫实验检测认知行为,透射电镜观察海马突触超微结构。结果 C57 BL/6J小鼠24~ 26

  17. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  18. Effects of a Memory Training Program in Older People with Severe Memory Loss

    Science.gov (United States)

    Mateos, Pedro M.; Valentin, Alberto; González-Tablas, Maria del Mar; Espadas, Verónica; Vera, Juan L.; Jorge, Inmaculada García

    2016-01-01

    Strategies based memory training programs are widely used to enhance the cognitive abilities of the elderly. Participants in these training programs are usually people whose mental abilities remain intact. Occasionally, people with cognitive impairment also participate. The aim of this study was to test if memory training designed specifically for…

  19. Memory decay and loss of criticality in quorum percolation

    Science.gov (United States)

    Renault, Renaud; Monceau, Pascal; Bottani, Samuel

    2013-12-01

    In this paper, we present the effects of memory decay on a bootstrap percolation model applied to random directed graphs (quorum percolation). The addition of decay was motivated by its natural occurrence in physical systems previously described by percolation theory, such as cultured neuronal networks, where decay originates from ionic leakage through the membrane of neurons and/or synaptic depression. Surprisingly, this feature alone appears to change the critical behavior of the percolation transition, where discontinuities are replaced by steep but finite slopes. Using different numerical approaches, we show evidence for this qualitative change even for very small decay values. In experiments where the steepest slopes can not be resolved and still appear as discontinuities, decay produces nonetheless a quantitative difference on the location of the apparent critical point. We discuss how this shift impacts network connectivity previously estimated without considering decay. In addition to this particular example, we believe that other percolation models are worth reinvestigating, taking into account similar sorts of memory decay.

  20. Motivation for weight loss affects recall from autobiographical memory in dieters

    DEFF Research Database (Denmark)

    Johannessen, Kim Berg; Berntsen, Dorthe

    2009-01-01

    Two studies examined the connection between motivation for weight loss and autobiographical memory by comparing characteristics of autobiographical memories between dieters and non-dieters. Study 1 involved 29 normal/overweight dieters and 48 non-dieters, and Study 2 involved 18 obese dieters...... and 18 normal weight non-dieters. Memories recalled in response to dieting-related cue words were rated as more central to the person's identity and life story and contained more body- or weight-related elements for the dieters than the non-dieters. No differences between dieters and non-dieters were...

  1. The problem of arriving at a phenomenological description of memory loss.

    Science.gov (United States)

    Moyle, W; Clinton, M

    1997-07-01

    This paper discusses a methodological difficulty that arose when uncovering the conscious experience of being nurtured as an in-patient with depression on a psychiatric ward. It considers the problem of arriving at a phenomenological description of memory loss in a patient who had undergone electroconvulsive therapy (ECT). The paper begins by describing the prevalence of depression and its significance for nurses working in in-patient settings. Examples of empirical research into memory loss in depression are used to show what researchers must set aside if they are to arrive at a phenomenological description of memory loss. The choice of a phenomenological approach to the wider study from which the methodological problem discussed here arose is then justified. The phenomena of memory is introduced to show the methodological significance of attempting to arrive at a phenomenological description of the statement made by one of the participants, a woman being treated as an in-patient for major depression. A possible description of the phenomena of memory loss based on the existential phenomenology of Sartre is offered to call into question the ability of researchers to bracket their assumptions. The significance for nurses of the wider study from which our example is taken is then described. Finally it is argued that despite the methodological difficulty described, a phenomenological perspective based on the philosophy of Husserl can point nurses in the direction of meeting the human needs of their patients.

  2. Automata Networks Model of Memory Loss Effects on the Formation of Linguistic Conventions

    CERN Document Server

    Vera, Javier

    2015-01-01

    This paper proposes an Automata Networks approach to address the influence of memory loss on the formation of shared conventions. We focus our analysis on a numerical description of the dynamics over one and two dimensional periodic lattices, through an energy function that measures the local agreement between the individuals. For the two dimensional case, it exhibits a sharp transition on the relation between the energy and the parameter defined to measure the amount of memory loss. Finally, we briefly discuss the implications for the formation of language.

  3. Memory Loss, Alzheimer’s Disease and General Anesthesia: A Preoperative Concern

    Science.gov (United States)

    Thaler, Adam; Siry, Read; Cai, Lufan; García, Paul S.; Chen, Linda; Liu, RenYu

    2012-01-01

    Background The long-term cognitive effects of general anesthesia are under intense scrutiny. Here we present 5 cases from 2 academic institutions to analyze some common features where the patient’s or the patient family member has made a request to address their concern on memory loss, Alzheimer’s disease and general anesthesia before surgery. Methods Records of anesthesia consultation separate from standard preoperative evaluation were retrieved to identify consultations related to memory loss and Alzheimer’s disease from the patient and/or patient family members. The identified cases were extensively reviewed for features in common. We used Google® (http://www. google.com/) to identify available online information using “anesthesia memory loss” as a search phrase. Results Five cases were collected as a specific preoperative consultation related to memory loss, Alzheimer’s disease and general anesthesia from two institutions. All of the individuals either had perceived memory impairment after a prior surgical procedure with general anesthesia or had a family member with Alzheimer’s disease. They all accessed public media sources to find articles related to anesthesia and memory loss. On May 2nd, 2011, searching “anesthesia memory loss” in Google yielded 764,000 hits. Only 3 of the 50 Google top hits were from peer-reviewed journals. Some of the lay media postings made a causal association between general anesthesia and memory loss and/or Alzheimer’s disease without conclusive scientific literature support. Conclusion The potential link between memory loss and Alzheimer’s disease with general anesthesia is an important preoperative concern from patients and their family members. This concern arises from individuals who have had history of cognitive impairment or have had a family member with Alzheimer disease and have tried to obtain information from public media. Proper preoperative consultation with the awareness of the lay literature can

  4. Age-related skin changes

    Directory of Open Access Journals (Sweden)

    Božanić Snežana

    2012-01-01

    Full Text Available Age-related skin changes can be induced by chronological ageing, manifested in subcutaneous fat reduction, and photo-ageing eliciting increased elastotic substance in the upper dermis, destruction of its fibrilar structure, augmented intercellular substance and moderate inflammatory infiltrate. Forty-five biopsy skin samples of the sun-exposed and sun-protected skin were analyzed. The patients were both males and females, aged from 17 to 81 years. The thickness of the epidermal layers and the number of cellular living layers is greater in younger skin. The amount of keratohyaline granules is enlarged in older skin. Dermoepidermal junction is flattened and the presence of elastotic material in the dermis is pronounced with age. The amount of inflammatory infiltrate is increased, the fibrous trabeculae are thickened in older skin and the atrophy of the hypodermis is observed. Chronological ageing alters the fibroblasts metabolism by reducing their life span, capacity to divide and produce collagen. During ageing, the enlargement of collagen fibrils diminishes the skin elasticity.

  5. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

    Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

  6. Making Physical Activity Accessible to Older Adults with Memory Loss: A Feasibility Study

    Science.gov (United States)

    Logsdon, Rebecca G.; McCurry, Susan M.; Pike, Kenneth C.; Teri, Linda

    2009-01-01

    Purpose: For individuals with mild cognitive impairment (MCI), memory loss may prevent successful engagement in exercise, a key factor in preventing additional disability. The Resources and Activities for Life Long Independence (RALLI) program uses behavioral principles to make exercise more accessible for these individuals. Exercises are broken…

  7. Memory loss versus memory distortion: the role of encoding and retrieval deficits in Korsakoff patients' false memories.

    Science.gov (United States)

    Van Damme, Ilse; d'Ydewalle, Gery

    2009-05-01

    Recent studies with the Deese/Roediger-McDermott (DRM) paradigm have revealed that Korsakoff patients show reduced levels of false recognition and different patterns of false recall compared to controls. The present experiment examined whether this could be attributed to an encoding deficit, or rather to problems with explicitly retrieving thematic information at test. In a variation on the DRM paradigm, both patients and controls were presented with associative as well as categorised word lists, with the order of recall and recognition tests manipulated between-subjects. The results point to an important role for the automatic/controlled retrieval distinction: Korsakoff patients' false memory was only diminished compared to controls' when automatic or short-term memory processes could not be used to fulfil the task at hand. Hence, the patients' explicit retrieval deficit appears to be crucial in explaining past and present data. Results are discussed in terms of fuzzy-trace and activation-monitoring theories.

  8. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD...... a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  9. Age-related changes in task related functional network connectivity.

    Directory of Open Access Journals (Sweden)

    Jason Steffener

    Full Text Available Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.

  10. Cotinine prevents memory loss and diminishes Alzheimer's disease-like pathology

    Directory of Open Access Journals (Sweden)

    Laura Catalina Charry

    2015-05-01

    Full Text Available Alzheimer's disease (AD affects millions of people around the world and currently there are no effective therapies. Cotinine, a metabolite of nicotine, has been shown to be neuroprotective, prevent memory loss and reduce amyloid-β (Aβ plaque pathology in transgenic AD mice. The beneficial effect that cotinine has on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β. These pro-apoptotic factors promote neuronal survival and the synaptic plasticity processes underlying learning and memory in the hippocampus and cortex of wild type and AD mice. Cotinine has also shown to diminish depressive-like behavior in normal and chronically stressed mice. Additionally, the use of this compound in studies has resulted in an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices. It can be observed in multiple studies, that daily treatment of mice with cotinine reduced Aβ levels and plaque formation compared with vehicle treated mice, which had higher memory loss and depressive behavior. The beneficial effects of cotinine on brain function and good safety profile, suggest that it may be a potential new therapeutic agent against Alzheimer's disease.

  11. What drives sleep-dependent memory consolidation: greater gain or less loss?

    Science.gov (United States)

    Fenn, Kimberly M; Hambrick, David Z

    2013-06-01

    When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

  12. Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

    Directory of Open Access Journals (Sweden)

    Carl-Johan Boraxbekk

    2015-07-01

    Full Text Available Objective: It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods: 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results: Episodic memory performance improved significantly (p = 0.010 after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA. Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions: Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity.

  13. Modulation of working memory function by motivation through loss-aversion.

    Science.gov (United States)

    Krawczyk, Daniel C; D'Esposito, Mark

    2013-04-01

    Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered.

  14. Exercise enhances memory consolidation in the aging brain

    OpenAIRE

    Shikha eSnigdha; Christina ede Rivera; Milgram, Norton W.; Carl eCotman

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition...

  15. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  16. A rare functional haplotype of the P2RX4 and P2RX7 genes leads to loss of innate phagocytosis and confers increased risk of age-related macular degeneration.

    Science.gov (United States)

    Gu, Ben J; Baird, Paul N; Vessey, Kirstan A; Skarratt, Kristen K; Fletcher, Erica L; Fuller, Stephen J; Richardson, Andrea J; Guymer, Robyn H; Wiley, James S

    2013-04-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in Western countries and is diagnosed by the clinical appearance of yellow subretinal deposits called drusen. Genetic changes in immune components are clearly implicated in the pathology of this disease. We have previously shown that the purinergic receptor P2X7 can act as a scavenger receptor, mediating phagocytosis of apoptotic cells and insoluble debris. We performed a genetic association study of functional polymorphisms in the P2RX7 and P2RX4 genes in a cohort of 744 patients with AMD and 557 age-matched Caucasian control subjects. The P2X4 Tyr315Cys variant was 2-fold more frequent in patients with AMD compared to control subjects, with the minor allele predicting susceptibility to disease. Pairwise linkage disequilibrium was observed between Tyr315Cys in the P2RX4 gene and Gly150Arg in the P2RX7 gene, and these two minor alleles formed a rare haplotype that was overrepresented in patients with AMD (n=17) compared with control subjects (n=3) (odds ratio 4.05, P=0.026). Expression of P2X7 (wild type or variant 150Arg) in HEK293 cells conferred robust phagocytosis toward latex beads, whereas coexpression of the P2X7 150Arg with P2X4 315Cys variants almost completely inhibited phagocytic capacity. Fresh human monocytes harboring this heterozygous 150Arg-315Cys haplotype showed 40% reduction in bead phagocytosis. In the primate eye, immunohistochemistry indicated that P2X7 and P2X4 receptors were coexpressed on microglia and macrophages, but neither receptor was seen on retinal pigment epithelial cells. These results demonstrate that a haplotype including two rare variants in P2RX7 and P2RX4 confers a functional interaction between these two variant receptors that impairs the normal scavenger function of macrophages and microglia. Failure of this P2X7-mediated phagocytic pathway may impair removal of subretinal deposits and predispose individuals toward AMD.

  17. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Shan Duan; Haraldur Sigurdsson; Hjorvar Petursson; Zhenglin Yang; Yu Zhao; Bernstein, Paul S.; Jian Ge; Fridbert Jonasson; Einar Stefansson; Gudleif Helgadottir; Norman A Zabriskie; Thorlakur Jonsson; Asgeir Björnsson; Theodora Thorlacius

    2005-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in t...

  18. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    Science.gov (United States)

    Maillet, David; Schacter, Daniel L

    2016-01-08

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes.

  19. Age-Related Enhancement of a Protein Synthesis-Dependent Late Phase of LTP Induced by Low Frequency Paired-Pulse Stimulation in Hippocampus

    Science.gov (United States)

    Huang, Yan-You; Kandel, Eric R.

    2006-01-01

    Protein synthesis-dependent late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation (HFS). This form of L-LTP is reduced in the aged animal and is positively correlated with age-related memory loss. Here we report a novel form of protein synthesis-dependent late phase of LTP in the CA1 region of hippocampus induced by…

  20. Sarcopenia and Age-Related Endocrine Function

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2012-01-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

  1. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  2. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  3. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular diseas

  4. Recovering and Preventing Loss of Detailed Memory: Differential Rates of Forgetting for Detail Types in Episodic Memory

    Science.gov (United States)

    Sekeres, Melanie J.; Bonasia, Kyra; St-Laurent, Marie; Pishdadian, Sara; Winocur, Gordon; Grady, Cheryl; Moscovitch, Morris

    2016-01-01

    Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired,…

  5. For patients with age -related hearing loss of hearing aid fit ing method is analyzed%对于老年性听力损失患者助听器的验配方法进行分析

    Institute of Scientific and Technical Information of China (English)

    朱美林

    2014-01-01

    objective:focus for senile patients with hearing loss of hearing aid fit ing method and ef ect.Methods:to select the research object is early January to the end of December 2013,2012 during accept hearing -aid with 60 cases of senile patients with hearing loss,al patients were accepted hearing -aid,and strengthen the rehabilitation training.Results:the fit ing ef ect for only 1 case with poor fit ing ef ect for a total of 9 cases,good fit ing ef ect for a total of 50 cases,was as high as 98.33%.Conclusion:the light of the specific conditions of the patients with hearing loss,for patients to choose the appropriate hearing AIDS fit ing,and strengthen the rehabilitation training,to improve success rate of hearing aid fit ing.%目的:重点探索老年性听力损失患者助听器的验配方法及效果。方法:选取的研究对象是2012年1月初至2013年12月底期间接受助听器验配的60例老年性听力损失患者,所有患者均接受助听器验配,并加强康复训练。结果:验配效果为差的仅有1例,验配效果为良的总共有9例,验配效果为优的总共有50例,优良率高达98.33%。结论:结合听力损失患者的具体情况,为患者选择合适的助听器进行验配,并加强康复训练,有利于提高助听器验配成功率。

  6. When Planning Results in Loss of Control: Intention-Based Reflexivity and Working-Memory

    Directory of Open Access Journals (Sweden)

    Nachshon eMeiran

    2012-05-01

    Full Text Available In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed intention-based reflexivity. The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand. When the plans are practiced, intention based reflexivity depends on the prior availability of response codes in long-term memory. When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working memory limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared, proactive control tends to be relatively rigid.

  7. When planning results in loss of control: intention-based reflexivity and working-memory

    Science.gov (United States)

    Meiran, Nachshon; Cole, Michael W.; Braver, Todd S.

    2012-01-01

    In this review, the authors discuss the seemingly paradoxical loss of control associated with states of high readiness to execute a plan, termed “intention-based reflexivity.” The review suggests that the neuro-cognitive systems involved in the preparation of novel plans are different than those involved in preparation of practiced plans (i.e., those that have been executed beforehand). When the plans are practiced, intention-based reflexivity depends on the prior availability of response codes in long-term memory (LTM). When the plans are novel, reflexivity is observed when the plan is pending and the goal has not yet been achieved. Intention-based reflexivity also depends on the availability of working-memory (WM) limited resources and the motivation to prepare. Reflexivity is probably related to the fact that, unlike reactive control (once a plan is prepared), proactive control tends to be relatively rigid. PMID:22586382

  8. X-82 to Treat Age-related Macular Degeneration

    Science.gov (United States)

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  9. Genes, inflammation, and age-related diseases

    OpenAIRE

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying gen...

  10. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    María eLlorens-Martín

    2014-05-01

    Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  11. Selective alterations of neurons and circuits related to early memory loss in Alzheimer’s disease

    Science.gov (United States)

    Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

    2014-01-01

    A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits. PMID:24904307

  12. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  13. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  14. Results of submacular surgery in age-related macula degeneration

    OpenAIRE

    Laue, Jessica

    2010-01-01

    Due to a disruption of barrier function of the membrane Bruch and a change of the phagocities retinal pigment epithelial (rpe), exists possibility for progress of pathologist invasion of new vessels from the choroidea under the retina. On the position of the macula it will cause quick loss of central visual acuity. The most frequent cause for a choroidal neovascular membrane (CNV) is age-related macula degeneration (AMD); further causes are based on idiopathic or postinflammable reasons. ...

  15. A complement-microglial axis drives synapse loss during virus-induced memory impairment.

    Science.gov (United States)

    Vasek, Michael J; Garber, Charise; Dorsey, Denise; Durrant, Douglas M; Bollman, Bryan; Soung, Allison; Yu, Jinsheng; Perez-Torres, Carlos; Frouin, Arnaud; Wilton, Daniel K; Funk, Kristen; DeMasters, Bette K; Jiang, Xiaoping; Bowen, James R; Mennerick, Steven; Robinson, John K; Garbow, Joel R; Tyler, Kenneth L; Suthar, Mehul S; Schmidt, Robert E; Stevens, Beth; Klein, Robyn S

    2016-06-22

    Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Here we show that viral infection of adult hippocampal neurons induces complement-mediated elimination of presynaptic terminals in a murine WNV neuroinvasive disease model. Inoculation of WNV-NS5-E218A, a WNV with a mutant NS5(E218A) protein leads to survival rates and cognitive dysfunction that mirror human WNV neuroinvasive disease. WNV-NS5-E218A-recovered mice (recovery defined as survival after acute infection) display impaired spatial learning and persistence of phagocytic microglia without loss of hippocampal neurons or volume. Hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning show increased expression of genes that drive synaptic remodelling by microglia via complement. C1QA was upregulated and localized to microglia, infected neurons and presynaptic terminals during WNV neuroinvasive disease. Murine and human WNV neuroinvasive disease post-mortem samples exhibit loss of hippocampal CA3 presynaptic terminals, and murine studies revealed microglial engulfment of presynaptic terminals during acute infection and after recovery. Mice with fewer microglia (Il34(-/-) mice with a deficiency in IL-34 production) or deficiency in complement C3 or C3a receptor were protected from WNV-induced synaptic terminal loss. Our study provides a new murine model of WNV-induced spatial memory impairment, and identifies a potential mechanism underlying neurocognitive impairment in patients recovering from WNV neuroinvasive disease.

  16. Age-related changes in triathlon performances.

    Science.gov (United States)

    Lepers, R; Sultana, F; Bernard, T; Hausswirth, C; Brisswalter, J

    2010-04-01

    The aim of this study was two-fold: i) to analyse age-related declines in swimming, cycling, and running performances for Olympic and Ironman triathlons, and ii) to compare age-related changes in these three disciplines between the Olympic and Ironman triathlons. Swimming, cycling, running and total time performances of the top 10 males between 20 and 70 years of age (in 5 years intervals) were analysed for two consecutive world championships (2006 and 2007) for Olympic and Ironman distances. There was a lesser age-related decline in cycling performance (ptriathlon in cycling (>55 years) and running (>50 years), respectively. In contrast, an age-related decline in swimming performance seemed independent of triathlon distance. The age-related decline in triathlon performance is specific to the discipline, with cycling showing less declines in performance with age than swimming and running. The magnitude of the declines in cycling and running performance at Ironman distance is greater than at Olympic distance, suggesting that task duration exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  17. Mechanism of apoptosis of hair cell in the cochlea of age-related hearing loss%年龄相关听力损失小鼠耳蜗毛细胞的凋亡抑制剂治疗研究

    Institute of Scientific and Technical Information of China (English)

    张正民; 李胜利

    2011-01-01

    目的:观察年龄相关听力损失耳蜗毛细胞的死亡方式,探讨防治老年性耳聋的分子机制.方法:将NMF308nmf/nmf小鼠做为年龄相关听力损失动物模型,每组随机选择7只28d,30d和60d的NMF308nmf/nmf小鼠,用ABR和DPOAE测定听觉功能,用免疫荧光染色组织化学技术TUNEL,Caspase-3和PI(碘化丙啶)染色标记耳蜗毛细胞.结果:NMF308nmf/nmf小鼠从1月龄开始发生听力减退和毛细胞功能改变,到2月龄时出现明显的TUNEL阳性标记,是毛细胞凋亡的最早表现;Caspase-3激活表达的毛细胞凋亡现象稍晚出现;PI标记可见毛细胞细胞核固缩和碎片出现的时间从2月龄开始;到3月龄时该种小鼠听力基本丧失,耳蜗毛细胞严重缺失.结论:在老年性耳聋早期,首先出现DNA单链断裂,随后有Caspase-3信号途径的激活,导致耳蜗毛细胞凋亡是老年性耳聋的主要分子机制.%Objective: Age-related hearing loss (Presbycusis) is the most common type of sensory impairment in human being. However, the molecular mechanisms of the presbycusis remain unclear. Apoptosis of outer hair cells (OHCs) in the cochlea has been found in aging animals. Methods: In this study,we investigated the apoptosis of hair cell in the cochlea of age-related hearing loss generated by ENU mutagenesis. Results: The results showed that the nmf308 mice with progressive hair cell loss along a base to apex gradientwith age-related hearing loss. The cochlear OHCs reduced from 5-10% at 1 month to 100% at 3 month in the basal region. Substantial amounts of TUNEL-postive OHCs nuclei appeared at 1 month age. And activated caspase-3 labeling demonstrated that most OHCs appeared at 2 months age. Conclusion; These result suggest that DNA single strand break is attributed primarily to apoptosis of cochlear lesion, whereas the later stage of lesion expansion leads to activation of caspase-3 activity reduced with further progression of nuclear condensation in age-related

  18. ROLE OF AUTOPHAGY IN AGE-RELATED MUSCLE LOSS

    OpenAIRE

    Lo Verso, Francesca

    2014-01-01

    Autophagy is an ubiquitous degradation system, that is conserved through species. Cells activate autophagy to degrade long-lived proteins, damaged organelles or portions of cytoplasm, that are engulfed in double-membrane vesicles called autophagosomes, that ultimately fuse to lysosomes, where the cargo is degraded and breakdown products are recycled to sustain cellular energetic demands. Skeletal muscle is the most abundant tissue in mammals and controls 80% of the blood glucose. We have r...

  19. Vision rehabilitation of persons with age related macular degeneration.

    Science.gov (United States)

    Siemsen, Dennis W; Brown, William L

    2011-05-01

    As the population of the United States ages, there is an increase in the number of persons with age related macular degeneration (ARMD). Even as new prevention and treatment techniques are developed, the vision loss associated with ARMD may lead to loss of independence and quality of life. Low vision is a rehabilitative process designed to improve visual function and restore independence. This paper is a review of the current research related to low vision in the areas of magnification, contrast and illumination, reading, training, driving and outcomes assessment.

  20. Ingredient Losses during Melting Binary Ni-Ti Shape Memory Alloys

    Institute of Scientific and Technical Information of China (English)

    S.K. Sadrnezhaad; S. Badakhshan Raz

    2005-01-01

    Losses of the alloying elements during vacuum induction melting of the binary NiTi alloys were evaluated by visual observation and chemical analysis of the NiTi melted specimens and the scalp formed on the internal surface of the crucible. The results indicated that the major sources of the losses were (a) evaporation of the metals, (b) formation of the NiTi scalp and (c) the sprinkling drops splashed out of the melt due to the exothermic reactions occurring between Ni and Ti to form the NiTi parent phase. Quantitative evaluations were made for the metallic losses by holding the molten alloy for 0.5, 3, 5, 10 and 15 min at around 100℃ above the melting point inside the crucible.Chemical analysis showed that there existed an optimum holding time of 3 min during which the alloying elements were only dropped to a predictable limit. Microstructure, chemical composition, shape memory and mechanical properties of the cast metal ingots were determined to indicate the appropriate achievements with the specified 3 min optimum holding time.

  1. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  2. [Pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  3. Progressive memory loss for one year and visual changes for three months

    Directory of Open Access Journals (Sweden)

    Si-yuan FAN

    2014-08-01

    Full Text Available A 49-year-old Chinese male presented with memory loss and vision disturbances. Neurological examination revealed bilateral positive Babinski signs. Cognitive assessments showed cognitive impairments. Neuroimaging studies showed high-intensity signals on bilateral parietal lobes, occipital lobes, temporal lobes, the splenium of the corpus callosum, and pyramidal tracts. Plasma very long chain fatty acids (VLCFA assay was ordered and demonstrated abnormally high concentrations of C26:0, and abnormally high ratios of C24:0 and C26:0 to C22:0. This diagnosis was also supported by the pathogenic mutation detected in the ACBD1 gene. There was no significant adrenal insufficiency, so replacement therapy was not initiated. doi: 10.3969/j.issn.1672-6731.2014.08.018

  4. Memory

    Science.gov (United States)

    ... it has to decide what is worth remembering. Memory is the process of storing and then remembering this information. There are different types of memory. Short-term memory stores information for a few ...

  5. Folate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

    Aging is associated with increased risk of cardiovascular and neurodegenerative disorders and an increase in their risk factors, such as decreased concentrations of folate and increased concentrations of homocysteine. The association of folate and homocysteine with age-related disease and, most impo

  6. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  7. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  8. Age-Related Deficits in Conjunctive Representation of Complex Objects

    Science.gov (United States)

    Scheerer, Nichole; Marrone, Diano F.

    2014-01-01

    Although some evidence is consistent with the notion that distinct cortical systems support memory and perception, mounting evidence supports a representational-hierarchical view of cognition, which posits that distinctions lie in simple feature representations versus more complex conjunctive representations of many stimulus features simultaneously. Thus, typical memory tasks engage different regions from typical perception tasks because they inherently test information on opposing ends of this continuum. Memory deficits are reliably reported with age, but the tasks used to make these conclusions predominantly rely on conjunctive representations. To test the extent to which age-related deficits may be accounted for by perceptual processing, this study investigated discriminations involving conjunctive representations in older adults. Results show that adults aged 50 to 77 are impaired, relative to their younger counterparts, on discriminations requiring feature conjunctions, but not simple feature representations. These findings support recent data showing an agerelated decline in the ability to form conjunctive representations. Furthermore, these data suggest that some ‘mnemonic’ deficits associated with age may in fact be the result of deficits in perception rather than memory. PMID:25308561

  9. Nitroxide Pharmaceutical Development for Aging-Related Degeneration & Disease

    Directory of Open Access Journals (Sweden)

    Jacob A. Zarling

    2015-11-01

    Full Text Available Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP, Tempol Hydroxylamine (TP-H, and TP-H prodrug (OT-551 are evaluated in (1 nonsmokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2 elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3 elderly smoker or nonsmoker Age-related Macular Degeneration (AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and reducing low luminance deficit and night vision loss in dry AMD smokers and non-smoker patients. Topical, oral or injectable drug formulations are discussed.

  10. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra;

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  11. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  12. Depression in Age-Related Macular Degeneration

    OpenAIRE

    Casten,Robin; Rovner,Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depressio...

  13. Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit.

    Science.gov (United States)

    Aggleton, John P; Pralus, Agathe; Nelson, Andrew J D; Hornberger, Michael

    2016-07-01

    It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer's disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer's disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer's disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer's disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer's disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer's disease.

  14. 谷胱甘肽S-转移酶GSTT1、GSTM1基因多态性与老年性耳聋遗传易感性的关联性分析%Association analysis of GSTT1 and GSTM1 genes with hereditary susceptibility to age-related hearing loss among Chinese

    Institute of Scientific and Technical Information of China (English)

    朱玉华; 戴朴; 袁慧军; 翟所强

    2011-01-01

    Objective To determine the relationship between GSTM1 and GSTT1 genetic polymorphisms and hereditary susceptibility to age-related hearing loss. Methods Specimens in this study were selected from the database at the Deafness Molecular Diagnosis Center, Institute of Otorhinolaryngology, Chinese PLA General Hospital for genomic DNA extraction. The genetic polymorphisms of GSTM1 and GSTT1 were detected by multiplex polymerase chain reaction. The results were compared to the control and x2 test was used to determine the frequency and association of genotype of GSTM1 and GSTT1. Results This study included 224 specimens, including those from cases of age-related hearing loss (n= 110, PTA = 51 ± 11 dB HL) and from age-matched controls(n= 114, PTA = 18±4dB HL) All subjects were between 60° to 80 years of age. The average age of the age related hearing loss group (77 males and 33 females) was 72.93 ± 5.08 years, and that of the control group (76 males and 38 females) was 73.10 ± 5.787 years. Cenotyping and statistical analysis revealed no difference between patients with age related hearing loss and the controls regarding GSTM1, GSTT1 genotype positive rate and frequencies of GSTT1+/GSTW+, GSTT1+/GSTM1-, GSTT1-/GSTT1+ and GSTT1-/GSTM1- genotypes (P> 0.05). Conclusion We are unable to detect a strong association between GSTM1, GSTT1 gene and age related hearing loss in this Chinese population.%目的 探讨谷胱甘肽S-转移酶(glutathione S-transferase,GST)GSTT1和GSTM1基因多态性是否与老年性耳聋遗传易感性相关.方法 在解放军总医院耳鼻咽喉科研究所聋病分子诊断中心样本库中选取本研究的研究对象,提取基因组DNA;利用多重PCR(Polymerase chain reaction,PCR)的方法 同时扩增所有研究对象GSTT/GSTM基因编码区并进行GSTM1和GSTT1基因多态性的分型;通过病例-对照关联性分析方法 进行统计学分析,明确GSTT1和GSTM1的多态性和老年性耳聋遗传易感性是否相关.结果

  15. 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.

  16. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  17. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    Science.gov (United States)

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  18. Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Tapia-Rojas, Cheril; Aranguiz, Florencia; Varela-Nallar, Lorena; Inestrosa, Nibaldo C

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities, and the appearance of amyloid plaques composed of the amyloid-β peptide (Aβ) and neurofibrillary tangles formed of tau protein. It has been suggested that exercise might ameliorate the disease; here, we evaluated the effect of voluntary running on several aspects of AD including amyloid deposition, tau phosphorylation, inflammatory reaction, neurogenesis and spatial memory in the double transgenic APPswe/PS1ΔE9 mouse model of AD. We report that voluntary wheel running for 10 weeks decreased Aβ burden, Thioflavin-S-positive plaques and Aβ oligomers in the hippocampus. In addition, runner APPswe/PS1ΔE9 mice showed fewer phosphorylated tau protein and decreased astrogliosis evidenced by lower staining of GFAP. Further, runner APPswe/PS1ΔE9 mice showed increased number of neurons in the hippocampus and exhibited increased cell proliferation and generation of cells positive for the immature neuronal protein doublecortin, indicating that running increased neurogenesis. Finally, runner APPswe/PS1ΔE9 mice showed improved spatial memory performance in the Morris water maze. Altogether, our findings indicate that in APPswe/PS1ΔE9 mice, voluntary running reduced all the neuropathological hallmarks of AD studied, reduced neuronal loss, increased hippocampal neurogenesis and reduced spatial memory loss. These findings support that voluntary exercise might have therapeutic value on AD.

  19. Age-related perspectives and emotion processing.

    Science.gov (United States)

    Lynchard, Nicholas A; Radvansky, Gabriel A

    2012-12-01

    Emotion is processed differently in younger and older adults. Older adults show a positivity effect, whereas younger adults show a negativity effect. Socioemotional selectivity theory suggests that these effects can be elicited in any age group when age-related perspectives are manipulated. To examine this, younger and older adults were oriented to actual and age-contrasting possible selves. Emotion activations were assessed using lexical decision. In line with socioemotional selectivity theory, shifts in emotion orientation varied according to perspective, with both younger and older adults showing a negativity effect when a younger adult perspective was taken and a positivity effect when an older adult perspective was taken.

  20. [Age-related macular degeneration (AMD)].

    Science.gov (United States)

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  1. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Toft, Ulla; Linneberg, Allan;

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD....

  2. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  3. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  4. "Lose ten lbs in two weeks" Motivation for weight loss affects autobiographical memory in dieters

    DEFF Research Database (Denmark)

    Johannessen, Kim Berg; Berntsen, Dorthe

      The purpose of the present study was to examine the connection between motivation and autobiographical memories. Autobiographical memories recalled in response to dieting related versus neutral cue words were compared between a dieting and non-dieting group. Memories recalled in response...... higher on Beck's depression scale and had more recall errors in terms of overgeneral memories than the non-dieting group. The results can be seen to support the concept of current concerns (Klinger, 1978) and the theory of the working self (Conway & Pleydell-Pearce, 2000)....

  5. Age-related decline in associative learning in healthy Chinese adults.

    Science.gov (United States)

    Lee, Annie; Archer, Jo; Wong, Caroline Kai Yun; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2013-01-01

    Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.

  6. New approaches and potential treatments for dry age-related macular degeneration.

    Science.gov (United States)

    Damico, Francisco Max; Gasparin, Fabio; Scolari, Mariana Ramos; Pedral, Lycia Sampaio; Takahashi, Beatriz Sayuri

    2012-01-01

    Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  7. Meditation effects on cognitive function and cerebral blood flow in subjects with memory loss: a preliminary study.

    Science.gov (United States)

    Newberg, Andrew B; Wintering, Nancy; Khalsa, Dharma S; Roggenkamp, Hannah; Waldman, Mark R

    2010-01-01

    This preliminary study determined if subjects with memory loss problems demonstrate changes in memory and cerebral blood flow (CBF) after a simple 8-week meditation program. Fourteen subjects with memory problems had an IV inserted and were injected with 250 MBq of Tc-99m ECD while listening to a neutral stimulus CD. They then underwent a pre-program baseline SPECT scan. Then subjects were guided through their first meditation session with a CD, during which they received an injection of 925 MBq ECD, and underwent a pre-program meditation scan. Subjects completed an 8-week meditation program and underwent the same scanning protocol resulting in a post-program baseline and meditation scan. A region of interest (ROI) template obtained counts in each ROI normalized to whole brain to provide a CBF ratio. Baseline and meditation scans and neuropsychological testing were compared before and after the program. The meditation program resulted in significant increases (pmemory showed improvements after training. This preliminary study evaluated whether an 8-week meditation program resulted in improvements in neuropsychological function and differences in CBF in subjects with memory loss. While the findings are encouraging, there are a number of limitations that can be addressed in future studies with more participants and more detailed analyses.

  8. Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice.

    Science.gov (United States)

    Grizzell, J Alex; Iarkov, Alexandre; Holmes, Rosalee; Mori, Takahashi; Echeverria, Valentina

    2014-07-15

    Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint. Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests. These antidepressant and nootropic effects of cotinine were associated with an increase in the synaptophysin expression, a commonly used marker of synaptic density, in the hippocampus as well as the prefrontal and entorhinal cortices of restrained mice. The beneficial effects of cotinine in preventing various consequences of chronic stress were underscored by the inhibition of the glycogen synthase kinase 3 β in the hippocampus and prefrontal cortex. Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse.

  9. Motivation for Weight Loss affects recall from Autobiographical Memory in Dieters

    DEFF Research Database (Denmark)

    Johannessen, Kim Berg; Berntsen, Dorthe

    2008-01-01

    Two studies examined the connection between motivation and autobiographical memories. We expected memories recalled in response to dieting-related cue words to be more central to the person's identity and life story and to contain more body and weight related elements for dieters than for non...... the concept of current concerns and the theory of the working self....

  10. “Not Promising a Landfall …”: An Autotopographical Account of Loss of Place, Memory and Landscape

    Directory of Open Access Journals (Sweden)

    Jones, Owain

    2015-05-01

    Full Text Available This paper contributes to discussions about landscape and place and how they are practised in relation to time, displacement, memory and loss. I develop a multi-dimensional account of how landscape is generated in the moment by spatio-temporal topologies and topographies in which memory, movement and materiality play full parts. I consider absence, loss and displacement and how they operate within self-landscape practice, and how particular forms of materiality (in this case, large bridges become charged with all sorts of emotions relating to personal history (how bridges can be psychogeographical “hotspots”. Displacement from, or loss of, home/land/place/nature—driven by one means or another (economic, conflict, environmental degradations—can be a looming presence in everyday life. Resulting emotions and affective traces can suffuse through and cleave to materiality, and materiality patterned into landscape, in contingent, unexpected and unaccountable ways, which, as articulated through everyday affective life, are hard to represent in (academic language. Questions are raised about the relationships between self, time, memory, materiality and place, using a non-representational, creative approach, based on image and textual collage.

  11. Age-Related Factors That Influence Fertility

    Science.gov (United States)

    ... can be found at the NICHD Pregnancy Loss topic page . Committee on Gynecologic Practice of American College of ... 2012, from http://www.nichd.nih.gov/health/topics/pregnancyloss/researchinfo/Pages/default.aspx [top] « Lifestyle Factors That Influence Fertility ...

  12. Inflammation and its role in age-related macular degeneration.

    Science.gov (United States)

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.

  13. Update on Clinical Trials in Dry Age-related Macular Degeneration

    OpenAIRE

    Ibrahim Taskintuna; M.E. A. Abdalla Elsayed; Patrik Schatz

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age.related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age.Related Eye Disease Study 2 (AREDS2), implantable miniatu...

  14. Raspberry supplementation alleviates age-related motor dysfunction in select populations

    Science.gov (United States)

    Age-related declines in balance, muscle strength and coordination often lead to a higher incidence of falling. Among older adults, falls are the leading cause of distress, pain, injury, loss of confidence, and ultimately, loss of independence and death. Previous studies in our laboratory have demons...

  15. Exploring age-related brain degeneration in meditation practitioners.

    Science.gov (United States)

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  16. Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys

    OpenAIRE

    Patrick A Forcelli; Palchik, Guillermo; Leath, Taylor; DesJardin, Jacqueline T.; Gale, Karen; Malkova, Ludise

    2014-01-01

    Although the hippocampus has a well-documented role for spatial navigation across species, its role for spatial memory in nonnavigational tasks is uncertain. Thus, when monkeys are tested in tasks that do not require navigation through space, spatial memory seems unaffected by hippocampal lesions. However, the interpretation of these results is compromised by long-term compensatory adaptation occurring in the days and weeks after lesions. To preclude long-term compensation, we transiently ina...

  17. Vision Loss, Sudden

    Science.gov (United States)

    ... of age-related macular degeneration. Spotlight on Aging: Vision Loss in Older People Most commonly, vision loss ... Some Causes and Features of Sudden Loss of Vision Cause Common Features* Tests Sudden loss of vision ...

  18. Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline.

    Science.gov (United States)

    Shi, Qiaoqiao; Colodner, Kenneth J; Matousek, Sarah B; Merry, Katherine; Hong, Soyon; Kenison, Jessica E; Frost, Jeffrey L; Le, Kevin X; Li, Shaomin; Dodart, Jean-Cosme; Caldarone, Barbara J; Stevens, Beth; Lemere, Cynthia A

    2015-09-23

    The complement system is part of the innate immune response responsible for removing pathogens and cellular debris, in addition to helping to refine CNS neuronal connections via microglia-mediated pruning of inappropriate synapses during brain development. However, less is known about the role of complement during normal aging. Here, we studied the role of the central complement component, C3, in synaptic health and aging. We examined behavior as well as electrophysiological, synaptic, and neuronal changes in the brains of C3-deficient male mice (C3 KO) compared with age-, strain-, and gender-matched C57BL/6J (wild-type, WT) control mice at postnatal day 30, 4 months, and 16 months of age. We found the following: (1) region-specific and age-dependent synapse loss in aged WT mice that was not observed in C3 KO mice; (2) age-dependent neuron loss in hippocampal CA3 (but not in CA1) that followed synapse loss in aged WT mice, neither of which were observed in aged C3 KO mice; and (3) significantly enhanced LTP and cognition and less anxiety in aged C3 KO mice compared with aged WT mice. Importantly, CA3 synaptic puncta were similar between WT and C3 KO mice at P30. Together, our results suggest a novel and prominent role for complement protein C3 in mediating aged-related and region-specific changes in synaptic function and plasticity in the aging brain. Significance statement: The complement cascade, part of the innate immune response to remove pathogens, also plays a role in synaptic refinement during brain development by the removal of weak synapses. We investigated whether complement C3, a central component, affects synapse loss during aging. Wild-type (WT) and C3 knock-out (C3 KO) mice were examined at different ages. The mice were similar at 1 month of age. However, with aging, WT mice lost synapses in specific brain regions, especially in hippocampus, an area important for memory, whereas C3 KO mice were protected. Aged C3 KO mice also performed better on

  19. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome.

    Directory of Open Access Journals (Sweden)

    Alessandro Ghezzo

    Full Text Available Down Syndrome (DS is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years, from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier in DS persons, i.e. at an age where interventions can have the greatest efficacy.

  20. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

    Directory of Open Access Journals (Sweden)

    Cristiano Chiapinotto Spiazzi

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL or distilled water was administered via intracerebroventricular (i.c.v. injection. Selenofuranoside (5 mg/kg or vehicle (canola oil was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM and step-down passive-avoidance (SDPA tests. Antioxidant defenses along with reactive species (RS were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

  1. Nut consumption and age-related disease.

    Science.gov (United States)

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  2. The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource.

    Science.gov (United States)

    Rönnberg, Jerker; Hygge, Staffan; Keidser, Gitte; Rudner, Mary

    2014-01-01

    The UK Biobank offers cross-sectional epidemiological data collected on >500,000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138,098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task) and visuospatial, episodic long-term memory (i.e., a prospective memory task), with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.

  3. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  4. Nitroxide pharmaceutical development for age-related degeneration and disease.

    Science.gov (United States)

    Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.

  5. 绿茶多酚预防老龄C57 B L/6J小鼠学习记忆功能衰退实验研究%Green Tea Polyphenols Prevents the Age-related Decline of Learning and Memory Ability of C57BL/6J Mice

    Institute of Scientific and Technical Information of China (English)

    李琼; 李勇

    2009-01-01

    To investigate the effect of Green Tea Polyphenols (GTP) on the degeneration of learning and memory ability in aged C57BL/6J mice,14 month old C57BL/6J mice were randomly divided into aged control group and three GTP administration groups GTP was dissolved into the drinking water with a concentration of 0.025%,0.05% and 0.1%(W/V),respectively.After six months,the learning and memory abilities of the mice were checked by Morris water maze and step-down test.Thereafter,the serum of the mice was collected to measure the levels of SOD and GSH-Px.The protein levels of post synaptic density protein 95 (PSD95) and Ca~(2+)/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) were examined using Western blot 0.05% and 0.1% GTP administration can significantly shorten the escape latencies and swim distances of the mice in a place navigation test,increase the time spending in the target quadrant and the crossing numbers in a spatial probe test,and increase the latency to step down in the step-down test.It is shown,0.5% and 0.1% GTP administrations have significantly raised the activities of SOD and GSH-P_x in the serum and prevented the age-related reductions of two representative post synaptic density proteins PSD95 and CaMKⅡ.0.05% and 0.1% GTP in the drinking water can significantly prevent the decline of learning and memory ability in aged C57BL/6J mice.Besides its antioxidant ability,GTP may also regulate some learning and memory related proteins.%为了研究绿茶多酚对自然衰老的C57BL/6J小鼠学习记忆衰退的预防作用,将14月龄的C57BL/6J小鼠60只随机分为老年对照组和绿茶多酚低、中、高剂量干预组,绿茶多酚掺入小鼠饮水中,剂量分别为0.025%、0.05%和0.1%(W/V),另设1月龄青年对照组.干预6个月后,运用Morris水迷宫、跳台实验检测小鼠的空间学习记忆能力和被动回避记忆能力.结果发现,在Morris水迷宫实验中,0.05%和0.1%剂量的绿茶多酚干预能够明显缩短老年小鼠定

  6. Flying Blind: Aeromedical Certification and Undiagnosed Age-Related Macular Degeneration

    Science.gov (United States)

    2011-09-01

    or becomes worse over time Vision loss may be severe and rapid with wet AMD compared to dry AMD Distorted vision (i.e., metamorphopsia) - A grid of...Although.vision.loss.can.occur,.it. is.usually.minimal.and.progresses.slowly.(12) . The.“ wet ”.form.of.macular.degeneration.is.responsible. for.10...564-72 . 14 .. Michels. S,. Kurz-Levin. M .. [Age-related. macu- lar. degeneration. ( AMD )]. Ther Umsch .. 2009. Mar;66(3):189-95 . 15 .. Age-Related

  7. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

    Full Text Available The positivity effect refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather & Carstensen, 2005 scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision-making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people.

  8. Chronic intracerebroventricular administration of dimethyl sulfoxide attenuates streptozotocin-iduced memory loss in rats

    Directory of Open Access Journals (Sweden)

    Esmaeil Akbari

    2013-02-01

    Conclusion: Taken together, the results suggest that DMSO may be appropriate as adjuvant therapies for the prevention of memory impairment in the experimental models of AD. Therefore, use of DMSO as a solvent in AD animal studies should be considered having beneficial effects on cognitive function.

  9. PTEN, Longevity and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Izak S. Tait

    2013-12-01

    Full Text Available Since the discovery of PTEN, this protein has been shown to be an effective suppressor of cancer and a contributor to longevity. This report will review, in depth, the associations between PTEN and other molecules, its mutations and regulations in order to present how PTEN can be used to increase longevity. This report will collect recent research of PTEN and use this to discuss PTEN’s role in caloric restriction, antioxidative defense of DNA-damage and the role it plays in suppressing tumors. The report will also discuss that variety of ways that PTEN can be compromised, through mutations, complete loss of alleles and its main antagonist, the PI3K/AKT pathway.

  10. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

    Directory of Open Access Journals (Sweden)

    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  11. Action Mechanisms of Transcranial Direct Current Stimulation in Alzheimer’s Disease and Memory Loss

    OpenAIRE

    Hansen, Niels

    2012-01-01

    The pharmacological treatment of Alzheimer’s disease (AD) is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilita...

  12. Cognitive impairment and memory loss associated with histoplasmosis: a case study.

    Science.gov (United States)

    Loughan, Ashlee R; Perna, Robert; Hertza, Jeremy

    2014-01-01

    Histoplasmosis is a rare disease caused by inhalation of the fungus Histoplasma capsulatum. It can spread via cerebral circulation to the central nervous system as a manifestation of a disseminated infection; particularly in patients with immune suppression, which can result in isolated ring-enhancing lesions and inflammation in the brain. Of the reported disseminated histoplasmosis cases (approximately 1 in 2000 per year), only 5-20% have evidence of central nervous system involvement. This paper reviews a single case study of a 57-year-old female diagnosed with disseminated CNS histoplasmosis. Patient's complaints included reduced short-term memory, word-finding problems, and difficulty organizing, making decisions, getting lost while driving, recalling names, retaining information while reading, and slowed processing speed. There was also a history of mild depression and anxiety. Direct testing revealed deficits in multiple cognitive domains including complex attention, processing speed, semantic fluency, visual scanning, motor speed, set-shifting, naming, nonverbal memory, and verbal memory. Neuropsychological deficits suggest cortical and subcortical brain dysfunction, including anterior, temporal, and mesial-temporal regions. This case illustrates the need for neuropsychologists to understand histoplasmosis, the related pathophysiology, and the neuropsychological impact; particularly with the potential for delayed progression.

  13. New approaches and potential treatments for dry age-related macular degeneration

    OpenAIRE

    Francisco Max Damico; Fabio Gasparin; Mariana Ramos Scolari; Lycia Sampaio Pedral; Beatriz Sayuri Takahashi

    2012-01-01

    Emerging treatments for dry age-related macular degeneration (AMD) and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, ...

  14. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... Resources (3 links) BrightFocus Foundation: Macular Degeneration Treatment Macular Degeneration Partnership: Low Vision Rehabilitation Prevent Blindness America: Age-Related Macular Degeneration (AMD) ...

  15. Action mechanisms of transcranial direct current stimulation in Alzheimer´s disease and memory loss

    Directory of Open Access Journals (Sweden)

    Niels eHansen

    2012-05-01

    Full Text Available The pharmacological treatment of Alzheimer´s disease (AD is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS, a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson´s disease and stroke. TDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. Neurobiological mechanisms of AD comprise changes in neuronal activity and the cerebral blood flow caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation by degeneration of modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i neuronal activity and (ii human cerebral blood flow, (iii has synaptic and non-synaptic after-effects (iv, can modify neurotransmitters polarity-dependently, (v and alter oscillatory brain activity and (vi functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it might prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable to identify its therapeutic validity in other types of demential disorders.

  16. The memory remains: application of historical DNA for scaling biodiversity loss

    DEFF Research Database (Denmark)

    Eg Nielsen, Einar; Bekkevold, Dorte

    2012-01-01

    in the Columbia River, but also underpins the general significance of shifting baselines in conservation biology, and how to assess loss of genetic biodiversity. The results clearly illustrate the huge and versatile potential of using historical DNA in population and conservation genetics. Because...... now, no ‘smoking gun’ in terms of direct genetic evidence of the loss of a salmon ESU has been produced. In this issue of Molecular Ecology, Iwamoto et al. (2012) use microsatellite analysis of historical scale samples of Columbia River sockeye salmon (Oncorhynchus nerka) from 1924 (Fig. 1) to ask...

  17. Stereotactic radiotherapy in neovascular age-related macular degeneration

    Science.gov (United States)

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  18. Effect of NCAM on aged-related deterioration in vision.

    Science.gov (United States)

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging.

  19. Oxidative modification of proteins: age-related changes.

    Science.gov (United States)

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  20. Treatment of neovascular age-related macular degeneration: Current therapies

    Directory of Open Access Journals (Sweden)

    Albert J Augustin

    2009-01-01

    Full Text Available Albert J Augustin, Stefan Scholl, Janna KirchhofDepartment of Ophthalmology, Klinikum Karlsruhe, GermanyAbstract: Choroidal neovascularization (CNV secondary to age-related macular degeneration (AMD is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition.Keywords: wet AMD, neovascularization, PDT, steroids, anti-angiogenesis

  1. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  2. Mechanism of inflammation in age-related macular degeneration.

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  3. Gender differences in episodic memory and visual working memory including the effects of age.

    Science.gov (United States)

    Pauls, Franz; Petermann, Franz; Lepach, Anja Christina

    2013-01-01

    Analysing the relationship between gender and memory, and examining the effects of age on the overall memory-related functioning, are the ongoing goals of psychological research. The present study examined gender and age group differences in episodic memory with respect to the type of task. In addition, these subgroup differences were also analysed in visual working memory. A sample of 366 women and 330 men, aged between 16 and 69 years of age, participated in the current study. Results indicate that women outperformed men on auditory memory tasks, whereas male adolescents and older male adults showed higher level performances on visual episodic and visual working memory measures. However, the size of gender-linked effects varied somewhat across age groups. Furthermore, results partly support a declining performance on episodic memory and visual working memory measures with increasing age. Although age-related losses in episodic memory could not be explained by a decreasing verbal and visuospatial ability with age, women's advantage in auditory episodic memory could be explained by their advantage in verbal ability. Men's higher level visual episodic memory performance was found to result from their advantage in visuospatial ability. Finally, possible methodological, biological, and cognitive explanations for the current findings are discussed.

  4. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  5. Wet age related macular degeneration management and follow-up.

    Science.gov (United States)

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  6. Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Marielza Andrade Nunes

    Full Text Available The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd20Lms/2J and their non-transgenic litter mate genetic controls were treated with lithium carbonate (0.25mg/Kg/day in drinking water for 16 or 8 months starting at two and ten months of age, respectively [corrected]. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer's disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained.

  7. Spin pumping and inverse spin Hall effect in platinum: the essential role of spin-memory loss at metallic interfaces.

    Science.gov (United States)

    Rojas-Sánchez, J-C; Reyren, N; Laczkowski, P; Savero, W; Attané, J-P; Deranlot, C; Jamet, M; George, J-M; Vila, L; Jaffrès, H

    2014-03-14

    Through combined ferromagnetic resonance, spin pumping, and inverse spin Hall effect experiments in Co|Pt bilayers and Co|Cu|Pt trilayers, we demonstrate consistent values of ℓsfPt=3.4±0.4  nm and θSHEPt=0.056±0.010 for the respective spin diffusion length and spin Hall angle for Pt. Our data and model emphasize the partial depolarization of the spin current at each interface due to spin-memory loss. Our model reconciles the previously published spin Hall angle values and explains the different scaling lengths for the ferromagnetic damping and the spin Hall effect induced voltage.

  8. An intervention to maximize medication management by caregivers of persons with memory loss: Intervention overview and two-month outcomes.

    Science.gov (United States)

    Lingler, Jennifer H; Sereika, Susan M; Amspaugh, Carolyn M; Arida, Janet A; Happ, Mary E; Houze, Martin P; Kaufman, Robert R; Knox, Melissa L; Tamres, Lisa K; Tang, Fengyan; Erlen, Judith A

    2016-01-01

    Overseeing medication-taking is a critical aspect of dementia caregiving. This trial examined a tailored, problem-solving intervention designed to maximize medication management practices among caregivers of persons with memory loss. Eighty-three community-dwelling dyads (patient + informal caregiver) with a baseline average of 3 medication deficiencies participated. Home- and telephone-based sessions were delivered by nurse or social worker interventionists and addressed basics of managing medications, plus tailored problem solving for specific challenges. The outcome of medication management practices was assessed using the Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and an investigator-developed Medication Deficiency Checklist (MDC). Linear mixed modeling showed both the intervention and usual care groups had fewer medication management problems as measured by the MedMaIDE (F = 6.91, p importance of medication adherence, there may be benefit.

  9. The essential role of spin-memory loss at 3d/5d metallic interfaces in spin pumping

    Science.gov (United States)

    Jaffres, Henri

    2015-03-01

    I will present a review of experiments and theory of spin-pumping in Co/(Cu)/Pt 3d/5d metallic systems in the ferromagnetic resonance (FMR) regime of spin injection. By combining i) FMR analyses of the resonance linewidth of the Co spectra in contact with the Pt (or Cu/Pt) reservoir and ii) detection of the inverse spin-hall effect signal vs. Pt thickness, we were able to evidence two different lengthscales for the spin-current profile generated or absorbed at the interfaces. The first lenghscale, extracted from FMR analyses and of the order of 2 nm, represents a typical interface length characteristic of a spin memory loss at the Co/Pt and Co/Cu/Pt interfaces. This represent a typical region of spin-current dissipation by which almost 60-70 % of the total current generated is lost before conversion in bulk Pt. The second lengthscale, roughly equal to 3.4 nm, like determined by Inverse Spin Hall Effect (ISHE) transverse voltage measurement, is more characteristic of the spin-diffusion length of the bulk Pt that governs a part of the spin-to-charge conversion efficiency by ISHE. After careful analyses, we determined a spin-hall angle of 5.6 % for Pt and an intrinsic spin hall conductivity of 3200 (Ohm.cm)-1 for our corresponding Pt resistivity. In the end, I will focus on the physical description of our experiments within a derived Valet-Fert model describing the spin transport/relaxation in a diffusive approach and using relevant boundary conditions for spin-pumping (constant spin accumulation in the ferromagnet). The origin of the spin-memory loss and spin-current discontinuity, also proposed in a very recent work, will be explained in terms of atomic intermixing at interfaces or possible Rashba-split states at Co/Pt interfaces.

  10. Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women.

    Science.gov (United States)

    Rubin, Leah H; Meyer, Vanessa J; J Conant, Rhoda; Sundermann, Erin E; Wu, Minjie; Weber, Kathleen M; Cohen, Mardge H; Little, Deborah M; Maki, Pauline M

    2016-08-01

    Deficits in verbal learning and memory are a prominent feature of neurocognitive function in HIV-infected women, and are associated with high levels of perceived stress. To understand the neurobiological factors contributing to this stress-related memory impairment, we examined the association between stress, verbal memory, and brain volumes in HIV-infected women. Participants included 38 HIV-infected women (Mean age=43.9years) from the Chicago Consortium of the Women's Interagency HIV Study (WIHS). Participants underwent structural magnetic resonance imaging (MRI) and completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10; PSS-10). Brain volumes were evaluated in a priori regions of interest, including the medial temporal lobe (MTL) and prefrontal cortex (PFC). Compared to HIV-infected women with lower stress (PSS-10 scores in lower two tertiles), HIV-infected women with higher stress (scores in the top tertile), performed worse on measures of verbal learning and memory and showed smaller volumes bilaterally in the parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus (p'slearning and memory performance. Prefrontal cortical atrophy is associated with stress-related deficits in verbal learning and memory in HIV-infected women. The time course of these volume losses in relation to memory deficits has yet to be elucidated, but the magnitude of the volumetric differences between women with higher versus lower stress suggests a prolonged vulnerability due to chronic stress and/or early life trauma.

  11. The rapidly evolving diagnosis and treatment of age-related macular degeneration.

    Science.gov (United States)

    2009-02-01

    Breakthrough research on age-related macular degeneration is stimulating the development of treatments, improving diagnosis, facilitating prevention through proper nutrition, and providing long-sought documentation on the effectiveness of low vision rehabilitation.Optometrists must take the lead in ensuring that patients reap the benefits. The February observance of Age-Related Macular Degeneration (AMD)/Low Vision Awareness Month provides a good time for optometrists to review their approach to age-related vision loss,ensure that they are ready to provide, or refer patients for, the best possible care, and prepare to conduct education efforts to ensure that their patients, communities, and other healthcare providers are aware of recent advancements.

  12.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  13. Attenuating age-related learning deficits: emotional valenced feedback interacts with task complexity.

    Science.gov (United States)

    Gorlick, Marissa A; Giguère, Gyslain; Glass, Brian D; Nix, Brittany N; Mather, Mara; Maddox, W Todd

    2013-04-01

    Previous research reveals that older adults sometimes show enhanced processing of emotionally positive stimuli relative to negative stimuli, but that this positivity bias reverses to become a negativity bias when cognitive control resources are less available. In this study, we test the hypothesis that emotionally positive feedback will attenuate well-established age-related deficits in rule learning whereas emotionally negative feedback will amplify age deficits-but that this pattern will reverse when the task involves a high cognitive load. Experiment 1 used emotional face feedback and revealed an interaction among age, valence of the feedback, and task load. When the task placed minimal load on cognitive control resources, happy-face feedback attenuated age-related deficits in initial rule learning and angry-face feedback led to age-related deficits in initial rule learning and set shifting. However, when the task placed a high load on cognitive control resources, we found that angry-face feedback attenuated age-related deficits in initial rule learning and set shifting whereas happy-face feedback led to age-related deficits in initial rule learning and set shifting. Experiment 2 used less emotional point feedback and revealed age-related deficits in initial rule learning and set shifting under low and high cognitive load for point-gain and point-loss conditions. The research presented here demonstrates that emotional feedback can attenuate age-related learning deficits-but only positive feedback for tasks with a low cognitive load and negative feedback for tasks with high cognitive load.

  14. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    Directory of Open Access Journals (Sweden)

    Bruce eCrosson

    2015-05-01

    Full Text Available The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  15. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease.

    Science.gov (United States)

    Crosson, Bruce; McGregor, Keith M; Nocera, Joe R; Drucker, Jonathan H; Tran, Stella M; Butler, Andrew J

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  16. Effects of Electroacupuncture at Tinggong and Yifeng on MDA Expression in Auditory Center of Guinea Pigs with Age-related Hearing Loss by D-galactose%电针耳穴对D-半乳糖致年龄相关性听力损失豚鼠听觉中枢丙二醛表达的影响

    Institute of Scientific and Technical Information of China (English)

    谢仕津; 殷泽登; 李君梅; 赖丹; 欧小毅; 黎万荣

    2012-01-01

    Objective To investigate the effects of maiondiaidchydc (MDA) , and the effects and mechanisms of clcctroacupuncturc on auditory center of guinea pigs with age-related hearing loss (AHL) by D-galactosc. Methods Thirty of 2- month -old guinea pigs were divided into 3 groups. The guinea pigs of the D - galactosc and clcctroacupuncturc (DE, n=10), and D-galactosc groups (n=10) were subcutancously injected D-galactosc (300 mg/kg. Day) , and the DE group were clcctroacupuncturcd at Tingggong and Yifcng for 6wccks. The control group (CG, n=10) was injected the same dose of physiological saline. The fourth group included 10 of 2-year -old guinea pigs. After 6 weeks, ABR were tested, and MDA expression in auditory cortex, inferior colliculus and cochlcar nucleus of all guinea pigs were quantitatcd by the TBA method. The data were analyzed using analysis of variance. Results 1. There was a significant increase in the average latent period of the third wave of ABR of the DG (P<0. 05 , compared with the CG) , and decrease in the DEG (P<0. 05 , compared with the DG). 2. There was an increase in MDA expression of the auditory cortex, inferior colliculus and cochlcar nucleus in the DG and 2 - year -old group (P<0. 05 , compared with the CG) , a decrease in the DEG (P<0. 05 , compared with the DG) , and nosignificant changes in the 2-year -old group (P<0. 05 , compared with the DG). Conclusion The aging of the auditory center would be related with the lipid pcroxidation induced by the increase of MDA. Klcctroacupuncturc at Tingggong and Yifcng of the guinea pig maybe effective partly inhibit the aging process of the auditory center.%目的 探讨丙二醛在豚鼠年龄相关性听力损失发病中的作用和电针对年龄相关性听力损失的防治作用及机制.方法 4月龄豚鼠30只分为三组,每组10只,D-半乳糖模型组:豚鼠颈背部皮下注射D-半乳糖300 mg·kg-1·d-1,每日1次,连续注射6周;D-半乳糖+电针组:D-半乳糖的用法用量同模型

  17. The Effects of Electroacupuncture at Tinggong and Yifeng on β-catenin Expression in Auditory Center of Guinea Pig with Age-related Hearing Loss%电针耳穴对年龄相关性听力损失豚鼠听觉中枢β-catenin表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘淑云; 邓力强; 杨烨; 殷泽登

    2016-01-01

    目的:探讨电针耳穴对D -半乳糖所致的年龄相关性听力损失豚鼠模型听觉中枢β-链蛋白(β-catenin)表达的影响。方法取3月龄豚鼠30只,随机分成三组:D -半乳糖模型组、D -半乳糖+电针组和对照组,每组各10只;18月龄豚鼠10只作为自然老化组。D-半乳糖模型组给予D -半乳糖(300 mg · kg -1· d-1)颈背部皮下注射,每天1次,连续6周;对照组给予等量生理盐水注射相同部位、相同频次、持续相同时间;D -半乳糖+电针组给予相同剂量的D -半乳糖颈背部皮下注射,30 min后给予电针听宫穴和翳风穴治疗15分钟,每日1次,共6周。自然老化组豚鼠常规饲养。上述实验结束后采用蛋白质印迹(Western blot)方法检测四组豚鼠下丘和听皮层β-catenin蛋白的表达变化。结果①与对照组相比,D-半乳糖模型组和自然老化组豚鼠下丘β-catenin蛋白表达量下降;与D-半乳糖模型组相比,D -半乳糖+电针组下丘β-catenin蛋白表达量增加;②D -半乳糖模型和自然老化组豚鼠听皮层β-catenin蛋白表达量下降,D-半乳糖+电针组其表达量增加。结论β-catenin蛋白可能通过Wnt/β-catenin信号通路,调控细胞生长、分化及凋亡,参与下丘和听皮层的老化过程;电针听宫穴和翳风穴可能通过增加下丘和听皮层β-catenin蛋白表达,经Wnt/β-catenin信号通路延缓豚鼠年龄相关性听力损失的发生。%Objective To explore the effects of the application of electroacupuncture at Tinggong and Yifeng to theβ-catenin expression in auditory center of guinea pigs with age -related hearing loss (AHL) induced by D -galactose .Methods There were four groups .Thirty 3 -month -old guinea pigs were randomly divided into three groups including the D -galactose group (DG ,n=10) ,D-galactose and electroacupuncture group (DEG ,n=10) , and

  18. C57 BL/6J小鼠听力及耳蜗毛细胞活性的年龄相关性研究%Study of the Correction between the Age Related Hearing Loss and the Cytoactivity Factors of the Cochlear Hair Cell in C57BL/6J Mice

    Institute of Scientific and Technical Information of China (English)

    周良强; 吴绍苓; 王燕; 褚汉启; 崔永华

    2009-01-01

    Objective To establish the mice model of AHL, to investigate the relationship between AHL and the cytoactive factors of the cochlear hair cells in C57BL/6J mice, and to classify the presbycusis models of the C57BL/6J mice. Methods C57BL/6J mice were divided into 6 experimental groups by age (A: 3 months old(m), B: 8 m, C: 9 m, D: 10 m, F: 17 m, G: 18 m) . The auditory functions mice were measured by auditory brainstem response (ABR) with the stimulus click and toneburst at 6 kHz and 8 kHz. 3 months later, Groups C , G, E and H were tested again for ABR. After ABR testing, the cytoactive of the hair cells was detected by succinate dehydrogenase staining and surface preparation technique(two mice from each group except groups C and G). Results The ABR thresholds elevated with age, and the marked change of the cochlea was the degeneration of the cytoactive of the cochlear hair cells, especially those of the outer hair cells. In the beginning, the basement of the basal membrane suffered from the mitochondrion degeneration in the outer hair cells, then it spread to the top region. Subsequently, the inner hair cells were involved. Conclusion C57BL/6J mouse was a typical animal model for the AHL,and the main change of the cochlea was the degeneration of the hair cells, especially the outer hair cells. Thus, C57BL/6J mice can be used as a suitable animal model for the study of presbycusis.%目的 建立年龄相关性听力损失(age-related hearing loss,AHL)的小鼠动物模型,探讨C57BL/6J小鼠发生AHL与毛细胞活性变化的关系,并初步对C57BL/6J小鼠AHL模型进行AHL的病理分类.方法 按3、8、9、10、17、18月龄段分6组培育C57BL/6J小鼠,各组分别进行听性脑干反应(ABR)测试,对耳蜗毛细胞行琥珀酸脱氢酶染色并作基底膜硬铺片,观察各年龄段小鼠内外毛细胞线粒体琥珀酸脱氢酶的活性.结果 C57BL/6J小鼠随年龄增大,ABR阈值明显增高,在3月龄到9月龄期间ABR平均反应阈值增大

  19. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    Science.gov (United States)

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  20. New approaches and potential treatments for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  1. Session III: Mechanisms of age-related cognitive change and targets for intervention: inflammatory, oxidative, and metabolic processes.

    Science.gov (United States)

    Craft, Suzanne; Foster, Thomas C; Landfield, Philip W; Maier, Steven F; Resnick, Susan M; Yaffe, Kristine

    2012-06-01

    There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults.

  2. The potential effects of meditation on age-related cognitive decline: a systematic review.

    Science.gov (United States)

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  3. Auditory training can improve working memory, attention and communication in adverse conditions for adults with hearing loss

    Directory of Open Access Journals (Sweden)

    Melanie Ann Ferguson

    2015-05-01

    Full Text Available Auditory training (AT helps compensate for degradation in the auditory signal. A series of three high-quality training studies are discussed, (i a randomized controlled trial (RCT of phoneme discrimination in quiet that trained adults with mild hearing loss (n=44, (ii a repeated measures study that trained phoneme discrimination in noise in hearing aid (HA users (n=30, and (iii a double-blind RCT that directly trained working memory (WM in HA users (n=57. AT resulted in generalized improvements in measures of self-reported hearing, competing speech and complex cognitive tasks that all index executive functions. This suggests that for AT related benefits, the development of complex cognitive skills may be more important than the refinement of sensory processing. Furthermore, outcome measures should be sensitive to the functional benefits of auditory training. For WM training, lack of far-transfer to untrained outcomes suggests no generalized benefits to real-world listening abilities. We propose that combined auditory-cognitive training approaches, where cognitive enhancement is embedded within auditory tasks, are most likely to offer generalized benefits to the real-world listening abilities of adults with hearing loss.

  4. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects.

    Science.gov (United States)

    Mormino, E C; Kluth, J T; Madison, C M; Rabinovici, G D; Baker, S L; Miller, B L; Koeppe, R A; Mathis, C A; Weiner, M W; Jagust, W J

    2009-05-01

    Although beta-amyloid (Abeta) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via 'Pittsburgh Compound-B' (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Abeta and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Abeta deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Abeta deposition as the primary event in this cascade. This pattern suggests that declining EM in older individuals may be caused by Abeta-induced hippocampus atrophy.

  5. Quantifying age-related differences in information processing behaviors when viewing prescription drug labels.

    Directory of Open Access Journals (Sweden)

    Raghav Prashant Sundar

    Full Text Available Adverse drug events (ADEs are a significant problem in health care. While effective warnings have the potential to reduce the prevalence of ADEs, little is known about how patients access and use prescription labeling. We investigated the effectiveness of prescription warning labels (PWLs, small, colorful stickers applied at the pharmacy in conveying warning information to two groups of patients (young adults and those 50+. We evaluated the early stages of information processing by tracking eye movements while participants interacted with prescription vials that had PWLs affixed to them. We later tested participants' recognition memory for the PWLs. During viewing, participants often failed to attend to the PWLs; this effect was more pronounced for older than younger participants. Older participants also performed worse on the subsequent memory test. However, when memory performance was conditionalized on whether or not the participant had fixated the PWL, these age-related differences in memory were no longer significant, suggesting that the difference in memory performance between groups was attributable to differences in attention rather than differences in memory encoding or recall. This is important because older adults are recognized to be at greater risk for ADEs. These data provide a compelling case that understanding consumers' attentive behavior is crucial to developing an effective labeling standard for prescription drugs.

  6. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss

    Directory of Open Access Journals (Sweden)

    J. Schmitz

    2016-05-01

    Conclusions: These results demonstrate that although sustained weight loss improves systemic glucose homeostasis, primarily through improved inflammation and insulin action in liver, a remarkable obesogenic memory can confer long-term increases in adipose tissue inflammation and insulin resistance in mice as well as in a significant subpopulation of obese patients.

  7. Slowing down: age-related neurobiological predictors of processing speed

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    Mark A Eckert

    2011-03-01

    Full Text Available Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-relatedcognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed - dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging.

  8. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  9. Structural invariance and age-related performance differences in face cognition.

    Science.gov (United States)

    Hildebrandt, Andrea; Sommer, Werner; Herzmann, Grit; Wilhelm, Oliver

    2010-12-01

    Perceiving and memorizing faces swiftly and correctly are important social competencies. The organization of these interpersonal abilities and how they change across the life span are still poorly understood. We investigated changes in the mean and covariance structure of face cognition abilities across the adult life span. A sample of 448 participants, with age ranging from 18 to 88 years, completed a battery of 15 face cognition tasks. After establishing a measurement model of face cognition that distinguishes between face perception, face memory, and the speed of face cognition, we used multiple group models and age-weighted measurement models to explore age-related changes. The modeling showed that the loadings and intercepts of all measures are age invariant. The factor means showed substantial decrements with increasing age. Age-related decrements in performance were strongest for the speed of face cognition but were also salient for face perception and face memory. The onset of age decrements is apparent in the 60s for face perception, in the late 40s for face memory, and in the early 30s for speed of face cognition. Implications of these findings on a theoretical and methodological level are discussed, and potential consequences for applied settings are considered.

  10. Oxidative stress, innate immunity, and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE. These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD or choroidal neovascularization (CNV, or wet AMD. Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory

  11. Oxidative stress, innate immunity, and age-related macular degeneration.

    Science.gov (United States)

    Shaw, Peter X; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  12. The Difference that Age Makes: Cultural Factors that Shape Older Adults' Responses to Age-Related Macular Degeneration

    Science.gov (United States)

    Mogk, Marja

    2008-01-01

    This article suggests that approaching vision loss from age-related macular degeneration from a sociocultural perspective, specifically considering perceptions of aging, blindness, disability, and generational viewpoints and norms, may be critical to understanding older adults' responses to vision loss and visual rehabilitation.

  13. Influence of Age-Related Versus Non-Age-Related Renal Dysfunctionon Survival in Patients with Left Ventricular Dysfunction

    Science.gov (United States)

    Testani, Jeffrey M.; Brisco, Meredith A.; Han, Gang; Laur, Olga; Kula, Alexander J.; Cheng, Susan J.; Tang, W. H. Wilson; Parikh, Chirag R.

    2013-01-01

    Normal aging results in a predictable decline in glomerular filtration rate (GFR) and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age related declines in estimated GFR (eGFR) carry the same prognostic importance as disease attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337). The primary analysis focused on determining if the eGFR mortality relationship differed by the extent the eGFR was consistent with normal ageing. Mean eGFR was 65.7 ± 19.0ml/min/1.73m2. Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73m2 per year (95% CI 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted HR=1.0 per 10 ml/min/1.73m2, 95% CI 0.97–1.1, p=0.53) whereas a disease attributable decrease in eGFR above the median carried significant risk (adjusted HR=2.8, 95% CI 1.6–4.7, p<0.001). In conclusion, in the setting of LV dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID:24216124

  14. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  15. Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

    Science.gov (United States)

    Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

    2014-11-19

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.

  16. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

    OpenAIRE

    Aniruddha Agarwal; Kanika Aggarwal; Vishali Gupta

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have...

  17. Economic Burden of Bilateral Neovascular Age-Related Macular Degeneration: Multi-Country Observational Study

    OpenAIRE

    Alan F. Cruess; Gergana Zlateva; Xiao Xu; Gisele Soubrane; Daniel Pauleikhoff; Andrew Lotery; Jordi Mones; Ronald Buggage; Caroline Schaefer; Tyler Knight; Goss, Thomas F

    2008-01-01

    Background: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. Objective: To document the economic burden of bilateral NV-AMD, th...

  18. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    OpenAIRE

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anythin...

  19. Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

    OpenAIRE

    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-01-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch’s membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflam...

  20. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans

    OpenAIRE

    Othman Al Gwairi; Lyna Thach; Wenhua Zheng; Narin Osman; Little, Peter J

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch’s membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of d...

  1. Age-related differences in recall for words using semantics and prosody.

    Science.gov (United States)

    Sober, Jonathan D; VanWormer, Lisa A; Arruda, James E

    2016-01-01

    The positivity effect is a developmental shift seen in older adults to be increasingly influenced by positive information in areas such as memory, attention, and decision-making. This study is the first to examine the age-related differences of the positivity effect for emotional prosody. Participants heard a factorial combination of words that were semantically positive or negative said with either positive or negative intonation. Results showed a semantic positivity effect for older adults, and a prosody positivity effect for younger adults. Additionally, older adults showed a significant decrease in recall for semantically negative words said in an incongruent prosodically positive tone.

  2. The andropause and memory loss: is there a link between androgen decline and dementia in the aging male?

    Institute of Scientific and Technical Information of China (English)

    Robert S. Tan; Shou-Jin Pu

    2001-01-01

    Studies demonstrate a decline in androgens with age and this results in the andropause. The objective of this paper is to review the literature on hormonal changes that occur in the aging males and determine if there are associations between decreased testosterone, dehydroepiandrosterone (DHEA) and decreased cognitive function. Trials of androgen replacement and its impact on cognitive function will also be analyzed. Method of analysis will be by a thorough search of articles on MEDLINE, the Intemet and major abstract databases. Results of the author's own research in 302 men of the association of memory loss as a symptom in the andropause will be presented. In addition, the authors open trial of testosterone replacement in hypogonadic men with Alzheimer's disease will also be presented. The results of the author's trial will be compared with other investigators. High endogenous testosterone level predicted better performance on visual spatial tests in several studies, but not in all studies. Likewise, testosterone replacement in hypogonadic patients improved cognitive functions in some but not all studies. Testosterone has also been shown to improve cognitive function in eugonadal men. Several studies have shown that declines in DHEA may contribute to Alzheimer's disease and the results of double blind studies with DHEA replacement and its effect on cognition will also be presented. In summary, there is still no consensus that androgen replacement is beneficial in cognitive decline but this option may prove promising in some patients.

  3. Age-related structural and functional changes in the cochlear nucleus.

    Science.gov (United States)

    Frisina, Robert D; Walton, Joseph P

    2006-01-01

    Presbycusis - age-related hearing loss - is a key communication disorder and chronic medical condition of our aged population. The cochlear nucleus is the major site of projections from the auditory portion of the inner ear. Relative to other levels of the peripheral and central auditory systems, relatively few studies have been conducted examining age-related changes in the cochlear nucleus. The neurophysiological investigations suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons from old animals relative to young adults. Biochemical investigations of glycine inhibition in the cochlear nucleus are consistent with the functional aging declines of this inhibitory neurotransmitter system that affect complex sound processing. Anatomical reductions in neurons of the cochlear nucleus and their output pathways can occur due to aging changes in the brain, as well as due to age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea, particularly from the basal, high-frequency regions. Novel preventative and curative biomedical interventions in the future aimed at alleviating the hearing loss that comes with age, will likely emanate from increasing our knowledge and understanding of its neural and molecular bases. To the extent that this sensory deficit resides in the central auditory system, including the cochlear nucleus, future neural therapies will be able to improve hearing in the elderly.

  4. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  5. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  6. Pharmacogenetics and nutritional supplementation in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hampton BM

    2015-05-01

    Full Text Available Blake M Hampton, Jaclyn L Kovach, Stephen G Schwartz Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: The Age-Related Eye Disease Study (AREDS recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available. Keywords: Age-Related Eye Disease Study (AREDS, age-related macular degeneration, age-related maculopathy susceptibility 2 (ARMS2, complement factor H (CFH, pharmacogenetics, randomized clinical trial (RCT

  7. Age-related macular degeneration: current treatment and future options.

    Science.gov (United States)

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  8. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  9. Assessing age-related patterns in strategy selection on a mathematical problem-solving task.

    Science.gov (United States)

    Lamson, Nina; Rogers, Wendy A

    2008-05-01

    We examined age-related differences in strategy-choice behavior in 27 younger and 28 older adults. Participants solved 4 two-digit by two-digit multiplication problems. We expected them to initially calculate the answers but eventually switch to a retrieval strategy, recalling answers from memory. Three groups emerged: younger adults who met the criterion (20 consecutive, correct, retrieval trials selected and answered in time), older adults who met the criterion, and older adults who did not meet the criterion. Younger and older adults who met the criterion had similar performance patterns. Some older adults who did not meet the criterion were slower to learn, whereas others seemed to be averse to the retrieval strategy. Thus, older adult patterns in strategy choice are considerably more varied than younger adult patterns, suggesting different explanations for differences in memory performance.

  10. Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for neovascular age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Cihan; ünlü; Gurkan; Erdogan; Betul; Onal; Gunay; Betul; Ilkay; Sezgin; Akcay; Esra; Kardes

    2015-01-01

    <正>Dear Sir,Iam Dr.Cihanünlü,from the Department of Opthalmology,ümraniye Training and Research Hospital,Istanbul,Turkey.I write to present our study findings on subfoveal choroidal thickness(SFCT)changes after intravitreal bevacizumab(IVB)therapy for neovascular age-related macular degeneration(AMD).AMD is the leading cause of severe visual loss in adults older than 60y[1].Visual loss in late stages of AMD may be the result of one of the two processes:geographic atrophy(GA)or choroidal neovascularization(CNV).Many types of

  11. Developmental improvement and age-related decline in unfamiliar face matching.

    Science.gov (United States)

    Megreya, Ahmed M; Bindemann, Markus

    2015-01-01

    Age-related changes have been documented widely in studies of face recognition and eyewitness identification. However, it is not clear whether these changes arise from general developmental differences in memory or occur specifically during the perceptual processing of faces. We report two experiments to track such perceptual changes using a 1-in- 10 (experiment 1) and 1-in-1 (experiment 2) matching task for unfamiliar faces. Both experiments showed improvements in face matching during childhood and adult-like accuracy levels by adolescence. In addition, face-matching performance declined in adults of the age of 65 years. These findings indicate that developmental improvements and aging-related differences in face processing arise from changes in the perceptual encoding of faces. A clear face inversion effect was also present in all age groups. This indicates that those age-related changes in face matching reflect a quantitative effect, whereby typical face processes are engaged but do not operate at the best-possible level. These data suggest that part of the problem of eyewitness identification in children and elderly persons might reflect impairments in the perceptual processing of unfamiliar faces.

  12. Remembering with gains and losses: effects of monetary reward and punishment on successful encoding activation of source memories.

    Science.gov (United States)

    Shigemune, Yayoi; Tsukiura, Takashi; Kambara, Toshimune; Kawashima, Ryuta

    2014-05-01

    The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment.

  13. Age-Related Differences in Worry and Related Processes

    Science.gov (United States)

    Basevitz, Paul; Pushkar, Dolores; Chaikelson, June; Conway, Michael; Dalton, Connie

    2008-01-01

    This study investigated the hypothesis that older adults would show age-related reductions in the tendency to worry in both their retrospective accounts and through cross-sectional age comparisons with a sample of younger adults. We also sought to determine whether age differences would be evident in psychological processes associated with a…

  14. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved...

  15. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine;

    2014-01-01

    Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and...

  16. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  17. Oxidation stress role in age-related cataractogenesis

    Directory of Open Access Journals (Sweden)

    Žorić Lepša

    2010-01-01

    Full Text Available Introduction. Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress. Oxidation stress and its form caused by ultraviolet light-photo-oxidative stress - are considered to be crucial in the etiopatho­genesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens posses a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  18. Age-related differences in women's foot shape

    NARCIS (Netherlands)

    Ansuategui Echeita, Jone; Hijmans, Juha M.; Smits, Sharon; Van der Woude, Lucas H. V.; Postema, Klaas

    2016-01-01

    Purpose: Describe age-related differences in women's foot shape using a wide range of measurements and ages. Study design: Cross-sectional, observational study. Main outcome measurements: Six foot-shape measurements of each foot: foot lengths, ball widths, ball circumferences, low instep circumferen

  19. The Experience of Age-Related Macular Degeneration

    Science.gov (United States)

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  20. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  1. Age-related differences in Second Language Acquisition

    Institute of Scientific and Technical Information of China (English)

    严爽

    2016-01-01

    There are many factors affecting second language acquisition such as motivation, personality, intelligence, ap-titude, learning styles and so on. This paper focuses on one crucial factor-age. The author tries to explore the age-related differences among second language learners. The main reasons behind the differences and the implications are also discussed.

  2. A Context for Teaching Aging-Related Public Policy.

    Science.gov (United States)

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  3. Age-related maculopathy: A genetic and epidemiological approach

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline)

    2000-01-01

    textabstractIn the 19th century, age-related maculopathy (ARM) was described for the first time as an agerelated abnormality of the macula lutea. ARM consists of a variety of clinical signs, from the early stages with soft distinct drusen, indistinct drusen and pigment alterations up to the late st

  4. Loss Of Memory

    Institute of Scientific and Technical Information of China (English)

    高利平

    2005-01-01

    Many of us believe that a person's mind becomes less active as he grows older.But this is not .true,according to Dr.Lissy F.Jarvik,professor of psychiatry (精神病学)at the University of Califomia,Los Angeles,and a board member of the New Center for Aging at the Veterans Hospital.She has studied the mental functioning of aging person for several years.

  5. Status of memory loss.

    LENUS (Irish Health Repository)

    Iyer, Parameswaran Mahadeva

    2012-01-01

    A 72-year-old woman presented with first onset of seizure with no prior history of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus. MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy showed acute neuronal necrosis and astrocyte hyperplasia together with extensive amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial hyperplasia was present. Postmortem examination revealed extensive plaque and tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left temporal area. The presence of focal perivascular oligodendroglial hyperplasia in the left temporal cortex, combined with extensive plaque and tangle disease may have contributed to the focal status epilepticus in this patient. Although the presence of focal perivascular oligodendroglial hyperplasia has been reported in cases of temporal lobe epilepsy, it has not been reported as a cause of seizure in patients with Alzheimer\\'s disease previously. Further studies for clinical-pathologic correlation would be required to confirm this hypothesis.

  6. Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

    DEFF Research Database (Denmark)

    Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob;

    2015-01-01

    Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed...

  7. Running throughout middle-age improves memory function, hippocampal neurogenesis and BDNF levels in female C57Bl/6J mice.

    NARCIS (Netherlands)

    M.W. Marlatt; M.C. Potter; P.J. Lucassen; H. van Praag

    2012-01-01

    Age-related memory loss is considered to commence at middle-age and coincides with reduced adult hippocampal neurogenesis and neurotrophin levels. Consistent physical activity at midlife may preserve brain-derived neurotrophic factor (BDNF) levels, new cell genesis and learning. In the present study

  8. Classification of wet aged related macular degeneration using optical coherence tomographic images

    Science.gov (United States)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  9. Kihi-to, a herbal traditional medicine, improves Abeta(25–35-induced memory impairment and losses of neurites and synapses

    Directory of Open Access Journals (Sweden)

    Joyashiki Eri

    2008-08-01

    Full Text Available Abstract Background We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Methods Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Aβ(25–35-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Results Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Aβ(25–35-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Aβ(25–35 treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H and microtubule-associated protein (MAP2-positive neurites. Aβ(25–35-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP are substrates of calpain, and calpain is known to be involved in Aβ-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Aβ(25–35-evoked increase in

  10. Age Differences in Brain Activity during Emotion Processing: Reflections of Age-Related Decline or Increased Emotion Regulation?

    OpenAIRE

    2011-01-01

    Despite the fact that physical health and cognitive abilities decline with aging, the ability to regulate emotion remains stable and in some aspects improves across the adult life span. Older adults also show a positivity effect in their attention and memory, with diminished processing of negative stimuli relative to positive stimuli compared with younger adults. The current paper reviews functional magnetic resonance imaging studies investigating age-related differences in emotional processi...

  11. Ageism, age relations, and garment industry work in Montreal.

    Science.gov (United States)

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  12. Mitochondrial aging and age-related dysfunction of mitochondria.

    Science.gov (United States)

    Chistiakov, Dimitry A; Sobenin, Igor A; Revin, Victor V; Orekhov, Alexander N; Bobryshev, Yuri V

    2014-01-01

    Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

  13. Humanin and Age-related diseases: A new link?

    Directory of Open Access Journals (Sweden)

    Zhenwei eGong

    2014-12-01

    Full Text Available Humanin (HN is 24-amino acid mitochondria-associated peptide. Since its initial discovery over a decade ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response and response to stressors such as oxidative stress, ischemia and starvation. HN and its potent analogs have been shown to have beneficial effects in many age-related diseases including Alzheimer’s disease (AD, stroke, diabetes, myocardial ischemia and reperfusion (MI-R, atherosclerosis, amyotrophic lateral sclerosis (ALS and certain types of cancer both in vitro and in vivo. More recently, an association between HN levels, growth hormone/ insulin-like growth factor-1 (GH/IGF axis and life span was demonstrated using various mouse models with mutations in the GH/IGF axis. The goal of this review is to summarize the current understanding of the role of HN in aging and age-related diseases.

  14. Mechanisms of age-related macular degeneration and therapeutic opportunities.

    Science.gov (United States)

    van Lookeren Campagne, Menno; LeCouter, Jennifer; Yaspan, Brian L; Ye, Weilan

    2014-01-01

    As the age of the population increases in many nations, age-related degenerative diseases pose significant socioeconomic challenges. One of the key degenerative diseases that compromise quality of life is age-related macular degeneration (AMD). AMD is a multi-faceted condition that affects the central retina, which ultimately leads to blindness in millions of people worldwide. The pathophysiology and risk factors for AMD are complex, and the symptoms manifest in multiple related but distinct forms. The ability to develop effective treatments for AMD will depend on a thorough understanding of the underlying pathophysiology, risk factors, and driver molecular pathways, as well as the ability to develop useful animal models. This review provides an overview of the aforementioned aspects in AMD.

  15. An Immunologic Study on Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted...

  16. Stereotactic radiotherapy in neovascular age-related macular degeneration

    OpenAIRE

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

  17. The role of epigenetics in age-related macular degeneration

    OpenAIRE

    Gemenetzi, M; Lotery, A.J.

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research fo...

  18. The Burden of Age-Related Macular Degeneration

    OpenAIRE

    Jordana K. Schmier; Mechelle L. Jones; Halpern, Michael T.

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, bo...

  19. Binocular Refraction in Patients with Age-Related Macular Degeneration

    OpenAIRE

    Skrbek, Matěj

    2013-01-01

    We’ve been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used ...

  20. Vitreomacular traction and age-related macular degeneration.

    Science.gov (United States)

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  1. Mitochondrial sirtuins as therapeutic targets for age-related disorders.

    Science.gov (United States)

    Shih, Jennifer; Donmez, Gizem

    2013-03-01

    Sirtuins are a class of histone deacetylases that have a wide range of regulatory roles in the cell. Three sirtuins, SIRT3 to SIRT5, localize to and function within the mitochondria. Mitochondrial dysfunction is thought to be the underlying mechanism of several age-related diseases, such as metabolic syndrome, cancer, and neurodegeneration. This review examines current evidence that mitochondrial sirtuins are involved in regulating mitochondrial function and pathogenesis.

  2. Smoking and Age-Related Macular Degeneration: Review and Update

    Science.gov (United States)

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  3. Present and Possible Therapies for Age-Related Macular Degeneration

    OpenAIRE

    Muhammad Khan; Ketan Agarwal; Mohamed Loutfi; Ahmed Kamal

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment ...

  4. Smoking and Age-Related Macular Degeneration: Review and Update

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  5. Telomere length variations in aging and age-related diseases.

    Science.gov (United States)

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  6. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  7. Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

    Science.gov (United States)

    Rabbitt, Patrick; Ibrahim, Said; Lunn, Mary; Scott, Marietta; Thacker, Neil; Hutchinson, Charles; Horan, Michael; Pendleton, Neil; Jackson, Alan

    2008-01-01

    Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell "Culture Fair" Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses.

  8. Caffeine protects against memory loss induced by high and non-anxiolytic dose of cannabidiol in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Nazario, Luiza Reali; Antonioli, Régis; Capiotti, Katiucia Marques; Hallak, Jaime Eduardo Cecílio; Zuardi, Antonio Waldo; Crippa, José Alexandre S; Bonan, Carla Denise; da Silva, Rosane Souza

    2015-08-01

    Cannabidiol (CBD) has been investigated in a wide spectrum of clinical approaches due to its psychopharmacological properties. CBD has low affinity for cannabinoid neuroreceptors and agonistic properties to 5-HT receptors. An interaction between cannabinoid and purinergic receptor systems has been proposed. The purpose of this study is to evaluate CBD properties on memory behavioral and locomotor parameters and the effects of pre-treatment of adenosine receptor blockers on CBD impacts on memory using adult zebrafish. CBD (0.1, 0.5, 5, and 10mg/kg) was tested in the avoidance inhibitory paradigm and anxiety task. We analyzed the effect of a long-term caffeine pre-treatment (~20mg/L - four months). Also, acute block of adenosine receptors was performed in co-administration with CBD exposure in the memory assessment. CBD promoted an inverted U-shaped dose-response curve in the anxiety task; in the memory assessment, CBD in the dose of 5mg/Kg promoted the strongest effects without interfering with social and aggressive behavior. Caffeine treatment was able to prevent CBD (5mg/kg) effects on memory when CBD was given after the training session. CBD effects on memory were partially prevented by co-treatment with a specific A2A adenosine receptor antagonist when given prior to or after the training session, while CBD effects after the training session were fully prevented by adenosine A1 receptor antagonist. These results indicated that zebrafish have responses to CBD anxiolytic properties that are comparable to other animal models, and high doses changed memory retention in a way dependent on adenosine.

  9. On the definition of age-related norms for visual function testing.

    Science.gov (United States)

    Johnson, M A; Choy, D

    1987-04-15

    Cross-sectional psychophysical and electrophysiologic studies of aging indicate that visual function declines only slightly or not at all until age 50-60, at which time the decline in visual function rapidly accelerates. This accelerated loss of function may reflect an increased rate of natural cellular degradation, or it may reflect an increased proportion of subclinical pathology in the presumed normal older population. This paper provides a critical review of the changes in visual function that occur with age. The results of this review have implications for both the definition of age-matched control groups and for early detection of age-related pathology.

  10. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

    Science.gov (United States)

    Butterfield, D A; Kanski, J

    2001-07-15

    Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

  11. [Progression of treatment and researches in dry age related macular degeneration].

    Science.gov (United States)

    Zhang, Kaiyan; Tang, Shibo

    2015-03-01

    Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

  12. Exercise enhances memory consolidation in the aging brain

    Directory of Open Access Journals (Sweden)

    Shikha eSnigdha

    2014-02-01

    Full Text Available Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise, post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 minutes on a treadmill on memory consolidation in aged canines both right after, an hour after, and twenty-four hours after acute exercise training in concurrent discrimination, object location memory (OLM and novel object recognition (NOR tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at twenty-four hour post exercise and not right after or one hour after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days on OLM or till criterion were reached (for reversal learning task. We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  13. Exercise enhances memory consolidation in the aging brain.

    Science.gov (United States)

    Snigdha, Shikha; de Rivera, Christina; Milgram, Norton W; Cotman, Carl W

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long-term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 min on a treadmill) on memory consolidation in aged canines both right after, an hour after, and 24 h after acute exercise training in concurrent discrimination, object location memory (OLM), and novel object recognition tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at 24 h post-exercise and not right after or 1 h after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days) on OLM or till criterion were reached (for reversal learning task). We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  14. The role of epigenetics in age-related macular degeneration.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  15. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies.

  16. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  17. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  18. Nutritional Modulation of Age-Related Macular Degeneration

    OpenAIRE

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 20...

  19. Binocular refraction in patients with age-related macular degeneration.

    Science.gov (United States)

    Skrbek, Matej

    2013-04-01

    We've been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used to prismatic correction was spontaneous and non-problematic. Based on these results we expect to find possibly the most effective rehabilitation of vision in patients suffering from ARMD.

  20. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  1. Future Therapies of Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

  2. Age-Related Deficits of Dual-Task Walking: A Review

    Directory of Open Access Journals (Sweden)

    Rainer Beurskens

    2012-01-01

    Full Text Available This review summarizes our present knowledge about elderly people's problems with walking. We highlight the plastic changes in the brain that allow a partial compensation of these age-related deficits and discuss the associated costs and limitations. Experimental evidence for the crucial role of executive functions and working memory is presented, leading us to the hypothesis that it is difficult for seniors to coordinate two streams of visual information, one related to navigation through visually defined space, and the other to a visually demanding second task. This hypothesis predicts that interventions aimed at the efficiency of visuovisual coordination in the elderly will ameliorate their deficits in dual-task walking.

  3. Neuroprotective effects of behavioural training and nicotine on age-related deficits in spatial learning.

    Science.gov (United States)

    Carrasco, Carmen; Vicens, Paloma; Redolat, Rosa

    2006-09-01

    Studies in humans and animals show a clear decline in spatial memory with age and several approaches have been adopted to alleviate this impairment. The purpose of our review is to assess the studies that have suggested the possible neuroprotective actions of behavioural training and nicotine-applied both independently and in conjunction-on age-related deficits in spatial learning. Both spatial pretraining and nonspatial experiences influence an animal's performance in spatial tasks. In aged rats, the experience of training in the water maze task increases the number of newly generated neurons in the hippocampus. The neuroprotective effects of nicotine have been demonstrated in both in-vitro and in-vivo models, although the molecular mechanisms underlying these actions are not yet fully understood. It had been concluded in different studies that nicotine can improve, impair or have no effect on performance in the water maze. Neurobiological data also suggest an interaction between nicotine and prior experience in complex tasks, although few studies have raised the question of whether nicotine treatment and training in spatial tasks may contribute in an interactive manner to alleviate spatial cognition impairment associated with the ageing process. Different findings suggest that past experience could be a confounding variable in longitudinal studies that aim to evaluate the neuroprotective effects of nicotine on age-related deficits in spatial learning.

  4. [Age-related macular degeneration: paradigm shift from recent findings].

    Science.gov (United States)

    Yanagi, Yasuo

    2015-03-01

    This review describes recent advances in age-related macular degeneration (AMD), based mainly on our own research findings. First, we investigated the effect of choroidal abnormality and found that choroidal hyperpermeability was observed more often in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD; however, even in eyes with typical AMD, substantial proportion of eyes showed hyperpermeability. Exudative AMD eyes with choroidal hyperpermeability showed thickened choroid more widely than previously demonstrated, and there were more frequent abnormalities with fundus autofluorescence examination. Thus, rather than classifying exudative AMD into PCV and typical AMD, AMD classification by choroidal hyperpermeability may be useful in illustrating the difference of certain clinical characteristics. Second, we investigated the importance of vitreomacular adhesion in the treatment outcome of exudative AMD. The currently prevailing hypothesis is that premacular VEGF concentration is lower in eyes with posterior vitreous detachment (PVD) than in eyes without PVD, thus leading to good treatment outcomes; however, in the current study, we showed that not only VEGF but also anti-angiogenic factor, interferon-inducible protein 10 (IP-10), is affected according to PVD. These results suggest that the effect of PVD on the intraocular environment is more complicated than previously thought, and may have diverse functions. Last, we explained the mechanism of AMD progression based mainly on our basic research. Our research showed that age-related decline of autophagic activity may, at least partly, contribute to the precursor lesion of AMD.

  5. Age-related changes to the production of linguistic prosody

    Science.gov (United States)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  6. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    Full Text Available BACKGROUND: Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms. METHODS AND FINDINGS: Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice. CONCLUSIONS: Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  7. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  8. Short-term blueberry-enriched antioxidant diet prevents and reverses object recognition memory loss in aged rats

    Science.gov (United States)

    Objective Previously, four months of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aged rats. Experiment 1 determined whether one and two-month BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the d...

  9. Age-related hearing decline in individuals with and without occupational noise exposure

    Directory of Open Access Journals (Sweden)

    Christina Hederstierna

    2016-01-01

    Full Text Available This study was conducted to compare the pattern of age-related hearing decline in individuals with and without self-reported previous occupational noise exposure. This was a prospective, population-based, longitudinal study of individuals aged 70-75 years, from an epidemiological investigation, comprising three age cohorts. In total there were 1013 subjects (432 men and 581 women. Participants were tested with pure tone audiometry, and they answered a questionnaire to provide information regarding number of years of occupational noise exposure. There were no significant differences in hearing decline, at any frequency, for those aged 70-75 years between the noise-exposed (N= 62 men, 22 women and the nonexposed groups (N = 96 men, 158 women. This study supports the additive model of noise-induced hearing loss (NIHL and age-related hearing loss (ARHL. The concept of different patterns of hearing decline between persons exposed and not exposed to noise could not be verified.

  10. Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.

    Science.gov (United States)

    Agosta, Elisa; Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Di Desidero, Teresa; Sartini, Maria Sole; Nardi, Marco; Danesi, Romano; Bocci, Guido

    2012-07-01

    Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

  11. Age-related changes in neural control of posture

    NARCIS (Netherlands)

    Papegaaij, Selma

    2016-01-01

    As we get older many physiological functions decline, including muscle strength, flexibility, and memory. Also in the aging brain there are changes, such as shrinkage of its volume. Since we need our brain to keep our balance while standing, it seems likely that these changes also affect our balance

  12. Age-related macular degeneration: a guide for the primary care physician.

    Science.gov (United States)

    Hazin, Ribhi; Freeman, P David; Kahook, Malik Y

    2009-02-01

    Age-related macular degeneration (AMD) is the leading cause of visual loss in Americans over the age of 50 years. AMD often results in profound disability due to the disease destroying the macula, the part of the retina responsible for central visual acuity and color vision. Risk factors for AMD include age greater than 50, female gender, Caucasian race, cigarette smoking, and family history of AMD. African Americans and other racial or ethnic groups can be affected by AMD. Although there is no cure for AMD, early diagnosis and treatment may slow disease progression and minimize irreversible visual dysfunction. Individuals suffering from central vision loss from AMD often retain peripheral vision. These affected individuals can benefit from low vision therapy, visual rehabilitation, or both to maintain or enhance activities of daily living.

  13. Trypanosomiasis-Induced B Cell Apoptosis Results in Loss of Protective Anti-Parasite Antibody Responses and Abolishment of Vaccine-Induced Memory Responses

    Science.gov (United States)

    Radwanska, Magdalena; Guirnalda, Patrick; De Trez, Carl; Ryffel, Bernard; Black, Samuel; Magez, Stefan

    2008-01-01

    cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas. PMID:18516300

  14. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2008-05-01

    -cell independent IgM(+MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas.

  15. Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses.

    Science.gov (United States)

    Radwanska, Magdalena; Guirnalda, Patrick; De Trez, Carl; Ryffel, Bernard; Black, Samuel; Magez, Stefan

    2008-05-30

    -cell independent IgM(+)MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas.

  16. Aging related erectile dysfunction—potential mechanism to halt or delay its onset

    Science.gov (United States)

    Gonzalez-Cadavid, Nestor F.; Rajfer, Jacob

    2017-01-01

    Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one’s genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40’s, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient’s age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from “leaking” out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with

  17. Effect of an Enhanced Nose-to-Brain Delivery of Insulin on Mild and Progressive Memory Loss in the Senescence-Accelerated Mouse.

    Science.gov (United States)

    Kamei, Noriyasu; Tanaka, Misa; Choi, Hayoung; Okada, Nobuyuki; Ikeda, Takamasa; Itokazu, Rei; Takeda-Morishita, Mariko

    2017-03-06

    Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia. The pharmacological actions of insulin were investigated at different stages of memory impairment using a senescence-accelerated mouse-prone 8 (SAMP8) model. The results of spatial learning tests suggested that chronic intranasal administration of insulin with l-penetratin to SAMP8 slowed the progression of memory loss in the early stage of memory impairment. However, contrary to expectations, this strategy using penetratin was ineffective in recovering the severe cognitive dysfunction in the progressive stage, which involves brain accumulation of amyloid β (Aβ). Immunohistological examination of hippocampal regions of samples from SAMP8 in the progressive stage suggested that accelerated nose-to-brain insulin delivery had a partial neuroprotective function but unexpectedly increased Aβ plaque deposition in the hippocampus. These findings suggest that the efficient nose-to-brain delivery of insulin combined with noncovalent CPP strategy has different effects on dementia during the mild and progressive stages of cognitive dysfunction.

  18. Perceptual and Social Attributes Underlining Age-Related Preferences for Faces.

    Science.gov (United States)

    Kiiski, Hanni S M; Cullen, Brendan; Clavin, Sarah L; Newell, Fiona N

    2016-01-01

    , led to more positive evaluations of competence. The results are discussed within the context of an age-related decline in the differentiation of faces in memory. Our findings have important implications for a better understanding of age-related perceptual factors and cognitive determinants of social interactions with unfamiliar others across the adult lifespan.

  19. Perceptual and social attributes underlining age-related preferences for faces

    Directory of Open Access Journals (Sweden)

    Hanni SM Kiiski

    2016-08-01

    with older aged faces, led to more positive evaluations of competence. The results are discussed within the context of an age-related decline in the differentiation of faces in memory. Our findings have important implications for a better understanding of age-related perceptual factors and cognitive determinants of social interactions with unfamiliar others across the adult lifespan.

  20. Memory loss risk assessment for the students nearby high-voltage power lines-a case study.

    Science.gov (United States)

    Ghadamgahi, Mojgan; Monazzam, Mohammad Reza; Hosseini, Monireh

    2016-06-01

    With increasing sources of alternating current electromagnetic fields (EMFs) in everyday life, their possible harmful effects on human health are a main area of concern in many countries. Given that children are the most valuable assets of each country, it is of utmost importance to study the effect(s) of EMF exposure on various health aspects of members within this age group. The present research is the first systematic study of the effects of exposure to electric substations on the memory status of male students in the age group of 10 to 12 years. The flux density values of extremely low frequency magnetic field were measured at four elementary schools in Tehran in accordance with IEEE std 644-1994. The device was 3-axis (X, Y, and Z) Gauss Meter, model: TES-1394. The students from two schools nearby a high voltage electricity substation (at distances of 30 and 50 m) were selected as the exposed group, and the students of two other schools at further distances of 1390 and 610 m were considered as the control group. To determine the status of working memory in the students, the questionnaire was adapted from Wechsler Intelligence Scale for Children (WISC-IV). The completed questionnaires were analyzed by t test and chi-square using SPSS 20. The average magnetic flux density was 0.245 μT at case schools and 0.164 μT at control schools, P < 0.01. The demographic characteristics of the students in the two groups were not statistically different. However, the difference in working memory was significant at the level of 5 %. The results of the questionnaire data showed that students in the control group had better working memory compared to students in case group. The findings revealed a reverse correlation between magnetic flux density and working memory of students (R = -0.255). It is concluded that extremely low frequency magnetic field exposure may have a negative impact on the working memory of children, but further studies are necessary to reach a

  1. Age-related differences in attentional bias for emotional faces.

    Science.gov (United States)

    Tomaszczyk, Jennifer C; Fernandes, Myra A

    2014-01-01

    Past research suggests an aging-related positivity effect in orienting to faces. However, these studies have eschewed direct comparison of orienting when positive and negative faces are presented simultaneously, thereby potentially underestimating the degree to which emotional valence influences such effects. In the current study younger and older adults viewed face pairs for 1000 ms, and upon face-pair offset indicated the location of a dot that appeared in the former location of one of the faces, to assess attentional orienting. When shown negative-neutral pairs, both age groups were biased to attend to negative faces, but when shown positive-negative pairs only younger adults showed a bias toward negative; older adults showed a lack of orienting toward either emotional face. Results suggest younger adults have a negativity bias in attention orienting regardless of the valence of nearby stimuli, whereas older adults show an absence of this bias when positive information is present.

  2. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  3. [Etiology and pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Herrmann, P; Holz, F G; Charbel Issa, P

    2013-04-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in Germany. Due to the demographic development a further increase of affected patients is to be expected. Improved understanding of AMD pathogenesis resulted from the molecular biological approaches in recent years and showed an association of genetic factors with AMD. The complement factor H gene and the second high-risk locus ARMS2 in particular were found to contribute a significant risk for development of the disease. Ageing and environmental factors, such as smoking, modulate the individual genetic risk profile. A detailed understanding of the complex AMD pathogenesis is also relevant in ophthalmological practice to understand new treatment strategies. In this review we aim to give an overview of the interplay of ageing, external environmental factors and genetic risk variants leading to AMD.

  4. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

    Full Text Available Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  5. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... stem cells (MSCs) that are present in the bone marrow and are able to differentiate into cell types such as osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like cells. Because of the ease of their isolation and their extensive differentiation potential, MSCs are among the first...

  6. Metalloproteinases and metalloproteinase inhibitors in age-related diseases.

    Science.gov (United States)

    Gargiulo, Simona; Gamba, Paola; Poli, Giuseppe; Leonarduzzi, Gabriella

    2014-01-01

    Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS). This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

  7. The genetics of age-related macular degeneration.

    Science.gov (United States)

    Guymer, Robyn

    2001-07-01

    AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.

  8. AMO Teledioptric System for age-related macular degeneration

    Science.gov (United States)

    Chou, Jim-Son; Ting, Albert C.

    1994-05-01

    A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

  9. [Future methods of treatment in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.

  10. Wearable diagnostic system for age-related macular degeneration.

    Science.gov (United States)

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  11. Age-related differences in arithmetic strategy sequential effects.

    Science.gov (United States)

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  12. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    Visual selection of illusory ‘Kanizsa’ figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form – an instance of ‘global precedence’ in visual processing....... Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global....... Electrophysiologically, this effect was accompanied by an early (150-225 ms) ‘positivity posterior contralateral’ (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing...

  13. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith;

    2015-01-01

    , a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5 mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard...... for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.......OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  14. Nutritional modulation of age-related macular degeneration.

    Science.gov (United States)

    Weikel, Karen A; Chiu, Chung-Jung; Taylor, Allen

    2012-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.

  15. Traumatic pasts and the historical imagination: Symptoms of loss, postcolonial suffering, and counter-memories among African migrants.

    Science.gov (United States)

    Beneduce, Roberto

    2016-06-01

    This work aims to rethink the relationship between anthropology and cultural psychiatry from a historical perspective, through reflections on the dynamics of forgetting and remembering in the context of migration. While migrants' symptoms often bear cultural hallmarks of suffering, they also reveal images of a traumatic history, which resurface in moments of danger, uncertainty, and crisis. I claim these symptoms are allegories of a dispossessed past, and can be interpreted as counter-memories, as "palimpsests" of an eclipsed script. Trauma symptoms keep returning to a collective past, and thus can be considered a particular form of historical consciousness. Psychiatric diagnoses may obscure these counter-memories. In particular, the diagnostic category of posttraumatic stress disorder that is commonly attached to traumatic experiences in current clinical practice recognizes the truth of individual traumatic events, but at the same time contributes to concealing the political, racial, and historical roots of suffering.

  16. Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss.

    Directory of Open Access Journals (Sweden)

    Stéphane Richard

    2005-12-01

    Full Text Available The Src substrate associated in mitosis of 68 kDa (Sam68 is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive. Herein we report the generation of Sam68-null mice by homologous recombination. Aged Sam68-/- mice preserved their bone mass, in sharp contrast with 12-month-old wild-type littermates in which bone mass was decreased up to approximately 75%. In fact, the bone volume of the 12-month-old Sam68-/- mice was virtually indistinguishable from that of 4-month-old wild-type or Sam68-/- mice. Sam68-/- bone marrow stromal cells had a differentiation advantage for the osteogenic pathway. Moreover, the knockdown of Sam68 using short hairpin RNA in the embryonic mesenchymal multipotential progenitor C3H10T1/2 cells resulted in more pronounced expression of the mature osteoblast marker osteocalcin when differentiation was induced with bone morphogenetic protein-2. Cultures of mouse embryo fibroblasts generated from Sam68+/+ and Sam68-/- littermates were induced to differentiate into adipocytes with culture medium containing pioglitazone and the Sam68-/- mouse embryo fibroblasts shown to have impaired adipocyte differentiation. Furthermore, in vivo it was shown that sections of bone from 12-month-old Sam68-/- mice had few marrow adipocytes compared with their age-matched wild-type littermate controls, which exhibited fatty bone marrow. Our findings identify endogenous Sam68 as a positive regulator of adipocyte differentiation and a negative regulator of osteoblast differentiation, which is consistent with Sam68 being a modulator of bone marrow mesenchymal cell differentiation, and hence bone metabolism, in aged mice.

  17. Stuck in gear: age-related loss of variable gearing in skeletal muscle.

    Science.gov (United States)

    Holt, Natalie C; Danos, Nicole; Roberts, Thomas J; Azizi, Emanuel

    2016-04-01

    Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (Pmuscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age.

  18. [Treating age-related hearing loss: hearing aids are not very popular

    NARCIS (Netherlands)

    Snik, A.F.M.; Leijendeckers, J.M.; Marres, H.A.M.

    2013-01-01

    Presbycusis means the deterioration of hearing resulting from the ageing process. Presbycusis can greatly affect one's quality of life; impaired hearing restricts communication and untreated presbycusis could result in social isolation and even depression. Nevertheless, only a minority of elderly wi

  19. Age-related loss of calcium binding proteins in rabbit hippocampus

    NARCIS (Netherlands)

    deJong, GI; Naber, PA; VanderZee, EA; Thompson, LT; Disterhoft, JF; Luiten, PGM

    1996-01-01

    Using immunocytochemistry hippocampal levels of the calcium binding proteins calbindin 28K (CB) and parvalbumin (PV) was studied in young (1 month) to very old (60 month) Albino rabbits. Young (3 month) and senescent (30 month) Wistar rats were also examined to compare the distribution and age depen

  20. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

    Directory of Open Access Journals (Sweden)

    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  1. SATB2-Nanog axis links age-related intrinsic changes of mesenchymal stem cells from craniofacial bone

    Science.gov (United States)

    Xu, Rongyao; Ge, Jie; Fu, Yu; Zhang, Yuchao; Du, Yifei; Ye, Jinhai; Cheng, Jie; Jiang, Hongbing

    2016-01-01

    Bone mesenchymal stem cells (BMSCs) senescence contributes to age-related bone loss. The alveolar bone in jaws originates from neural crest cells and possesses significant site- and age-related properties. However, such intrinsic characteristics of BMSCs from alveolar bone (AB-BMSCs) and the underlying regulatory mechanisms still remain unknown. Here, we found that the expression of special AT-rich binding protein 2 (SATB2) in human AB-BMSCs significantly decreased with aging. SATB2 knockdown on AB-BMSCs from young donors displayed these aging-related phenotypes in vitro. Meanwhile, enforced SATB2 overexpression could rejuvenate AB-BMSCs from older donors. Importantly, satb2 gene- modified BMSCs therapy could prevent the alveolar bone loss during the aging of rats. Mechanistically, the stemness regulator Nanog was identified as the direct transcriptional target of SATB2 in BMSCs and functioned as a downstream mediator of SATB2. Collectively, our data reveal that SATB2 in AB-BMSCs associates with their age-related properties, and prevents AB-BMSCs senescence via maintaining Nanog expression. These findings highlight the translational potential of transcriptional factor-based cellular reprogramming for anti-aging therapy. PMID:27632702

  2. Age-related differences in attention and memory toward emotional stimuli.

    Science.gov (United States)

    Bi, Dandan; Han, Buxin

    2015-09-01

    From the perspectives of time perception and motivation, socioemotional selectivity theory (SST) postulates that in comparison with younger adults, older adults tend to prefer positive stimuli and avoid negative stimuli. Currently the cross-cultural consistency of this positivity effect (PE) is still not clear. While empirical evidence for Western populations is accumulating, the validation of the PE in Asians is still rare. The current study compared 28 younger and 24 older Chinese adults in the processing of emotional information. Eye-tracking and recognition data of participants in processing pictures with positive, negative, or neutral emotional information sampled from the International Affection Picture System were collected. The results showed less negative bias for emotional attention in older adults than in younger adults, whereas for emotional recognition, only younger adults showed a negative bias while older adults showed no bias between negative and positive emotional information. Overall, compared with younger adults, emotional processing was more positive in older adults. It was concluded that Chinese older adults show a PE.

  3. Age-related changes in antisaccade task performance: Inhibitory control or working-memory engagement?

    NARCIS (Netherlands)

    R.M. Eenshuistra; M.W. van der Molen; K.R. Ridderinkhof

    2004-01-01

    In antisaccade tasks, subjects are required to generate a saccade in the direction opposite to the location of a sudden-onset target stimulus. Compared to young adults, older adults tend to make more reflex-like eye movements towards the target, and/or show longer saccadic onset latencies on correct

  4. Intraoperative performance and longterm outcome of phacoemulsification in age-related cataract.

    Directory of Open Access Journals (Sweden)

    Dholakia Sheena

    2004-01-01

    Full Text Available PURPOSE: To evaluate intraoperative performance and longterm surgical outcome after phacoemulsification of age-related cataracts. METHODS: Prospective, observational, non-comparative study of 165 consecutive eyes undergoing phacoemulsification with nuclear sclerosis Grade I to III (Scale I to V. Preoperative evaluation included specular microscopy. Phacoemulsification was performed by a single surgeon using a standardised surgical technique under topical anaesthesia. Intraoperatively, effective phaco time (EPT, wound site thermal injury (WSTI, serious complications (eg. vitreous loss, posterior capsule rupture, zonulolysis and intraoperative posterior capsule opacification (plaque were evaluated. Postoperatively, posterior capsule opacification (PCO, Neodymium:YAG (Nd:YAG laser posterior capsulotomy rate, corneal endothelial count, best corrected visual acuity and cystoid macular oedema were evaluated. Eyes were examined at 6 months and then yearly for 3 years. RESULTS: Mean ages of 78 males and 87 females were 59.12 +/- 8.56 and 58.34 +/- 7.45 years respectively. EPT was 36 +/- 19 seconds and WSTI occurred in 7 eyes (4.7%. No serious intraocular complications occurred. Intraoperative posterior capsule opacification (plaque was present in 21 eyes (13.93%. Postoperatively, PCO occurred in 8 eyes (4.84% and Nd:YAG laser posterior capsulotomy was performed in 3 eyes (1.8%. Endothelial cell loss was 7.1% at 3 years follow-up. At the end of 3 years follow-up, 146 eyes (88.89% maintained a best corrected visual acuity of > or = 6/12. Cystoid macular oedema did not occur in any eye at 1 and 6 months′ follow-up. CONCLUSION: PCO rates and endothelial cell loss were acceptable. Consistent and reproducible outcome can be obtained after phacoemulsification of age related cataracts (grade I to III.

  5. A PROSPECTIVE CLINICAL STUDY TO EVALUATE RISK FACTORS FOR AGE RELATED MACULAR DEGENERATION IN CENTRAL INDIA

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    Kavita

    2013-10-01

    Full Text Available Age related macular degeneration (AMD is a leadi ng cause of irreversible blindness among the elderly worldwide affecting 30 - 50 million individuals. AMD is more common in developed world. AMD is characterized by central visual loss. Advanced AMD can be classified in broadly into two types: dry and wet fo rm. Several clear risk factors for the development and progression of age related macular degeneration have been established are advancing age, genetic factors, history of smoking ,white race, obesity, high dietary intake of vegetable fat, low dietary inta ke of antioxidants and zinc. This prospective non - interventional study was conducted from February 2011 to October 2012 in the Regional Institute of Ophthalmology, Hamidia Hospital, Bhopal, included patients who attended the eye OPD, retina clinic and eye ward and were diagnosed as a case of AMD. Present study included 174 patients out of which patients 79(45.39% were above the age of 70 years, with 51 (29.31% patients between 61 - 70 years and 44 cases (25.28% in the sixth decade. Male: female ratio was 0 .75: 1. 21 (12.06% patients have a positive family history of AMD. Most common risk factor identified in our study was chronic sun exposure (49.42% followed by hypertension in 41.8% patients. 25.26% cases gave history of smoking and raised serum cholest erol levels were seen in 14.28% cases. History of alcoholism was positive in 19.54% patients. Of the 174 cases in our present study 90 patients (51.72% were hypermetropic. Conclusion: Age related macular degeneration is a disease of elderly with risk fact ors, most of them are preventable. If timely proper measures are taken, a major cause of blindness can be prevented in elderly age group.

  6. Age-related decline in white matter tract integrity and cognitive performance: a DTI tractography and structural equation modeling study.

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    Voineskos, Aristotle N; Rajji, Tarek K; Lobaugh, Nancy J; Miranda, Dielle; Shenton, Martha E; Kennedy, James L; Pollock, Bruce G; Mulsant, Benoit H

    2012-01-01

    Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.

  7. Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits.

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    Sokolowski, Katie; Obiorah, Maryann; Robinson, Kelsey; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2013-12-01

    The developing brain is particularly sensitive to exposures to environmental contaminants. In contrast to the adult, the developing brain contains large numbers of dividing neuronal precursors, suggesting that they may be vulnerable targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature neurons in the CA1-3 region as well as neural stem cells (NSC) in the dentate gyrus (DG) hilus, which actively produce new neurons that migrate to the granule cell layer (GCL). Using this well-characterized NSC population, we examined the impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and subsequent adolescent learning and memory behavior. Assessing a range of exposures, we found that a single subcutaneous injection of 0.6 µg/g MeHg in P7 rats induced caspase activation in proliferating NSC of the hilus and GCL. This acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the hilus by 22% and the GCL by 27%, as well as reductions in neural precursor proliferation by 25%. In contrast, non-proliferative CA1-3 pyramidal neuron cell number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an adolescent spatial memory deficit as assessed by Morris water maze. These results suggest that environmentally relevant levels of MeHg exposure may decrease NSC populations and, despite ongoing neurogenesis, the brain may not restore the hippocampal cell deficits, which may contribute to hippocampal-dependent memory deficits during adolescence.

  8. Age-related macular degeneration: beyond anti-angiogenesis.

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    Kent, David L

    2014-01-06

    Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate

  9. What associates Charles Bonnet syndrome with age-related macular degeneration?

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    Vojniković, Bozo; Radeljak, Sanja; Dessardo, Sandro; Zarković-Palijan, Tija; Bajek, Goran; Linsak, Zeljko

    2010-04-01

    Charles Bonnet syndrome (CBS) is a condition related to patients with visual loss due to age related macular degeneration or glaucoma that are having complex visual hallucinations. The CBS was first described by Swiss physician Charles Bonnet in 1760. Affected patients, who are otherwise mentally healthy people with significant visual loss, have vivid, complex recurrent visual hallucinations (VHs). One characteristic of these hallucinations is that they usually are "Lilliputian hallucinations" as patients experience micropsia (hallucinations in which the characters or objects are distorted and much smaller than normal). The prevalence of Charles Bonnet Syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. The high incidence of non-reported CBS is thought to be as a result of patient's fear to report the symptoms as they could be labeled as mentally insane since those type of visual hallucinations could be found in variety of psychiatric and neurological disorders such as drug or alcohol abuse (delirium tremens), Alice in Wonderland syndrome (AIWS), psychosis, schizophrenia, dementia, narcolepsy, epilepsy, Parkinson disease, brain tumors, migraine, as well as, in long term sleep deprivation. VHs can also be presented as the initial sign of the Epstein-Barr virus infection in infectious mononucleosis. Patients who suffer from CBS usually possess insight into the unreality of their visual experiences, which are commonly pleasant but may sometimes cause distress. The hallucinations consist of well-defined, organized, and clear images over which the subject has little control. It is believed that they represent release phenomena due to deafferentiation of the visual association areas of the cerebral cortex, leading to a form of phantom vision. Cognitive defects, social isolation, and sensory deprivation have also been implicated in the etiology of this condition. This study was conducted on 350 patients

  10. Role of intravitreal Bevacizumab Injection for Management of Neovascular Age Related Macular Degeneration

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    Neha K Desai

    2016-06-01

    Full Text Available Background: Age related macular degeneration ( ARMD is the major cause of severe visual loss in older adults. Different treatment modalities are available such as: Laser photocoagulation, photodynamic therapy,transpupillary thermotherapy,submacular surgery and anti-veg. Aims and Objectives: The aim of our study was to evaluate the efficacy and safety of intravitreally administered Bevacizumab a humanized monoclonal anti and ndash;VEGF in Neovascular Age related Macular Degeneration. Methodology: This non randomized, prospective study was carried out on 75 eyes of 75 patients attending the OPD at M and J Institute Of Ophthalmology and diagnosed as having Neovascular ARMD confirmed on FFA and SD-OCT . After taking written informed consent all patients were injected with intravitreal Bevacizumab 1.25 mg/0.05 ml. Follow up visits were scheduled one week, one month post procedure and every monthly thereafter. Results: 75 eyes of 75 patients were included in this non randomized prospective study. and 29.33% patients required 2 injections. Visual acuity is improved more than 3 lines from baseline in 21.33% patient, 64% patient have 2-3 lines gain and 6.66% patients showed 0-1 line gain in snellen's visual acuity. 5.33% patients have a loss of 1 line from baseline and 2.66% patients showed loss of 2-3 lines. Central foveal thickness decreased more than 200 microns from baseline in 52% patients, 28% patients have decreased of 100-200 microns and 20% patients have decreased of less than 100 microns. Discussion: Approximately 10 % of ARMD patients manifest the neovascular form of the disease. 12 weeks. Our study showed that 80% patients had decrease in central foveal thickness more than 100 microns from baseline at the end of one year. 85% patients had gain of 2 or more lines on Snellen's visual acuity chart from baseline.No patient had any serious local or systemic adverse reactions.Limitations of our study is small number of patients,ICG not done

  11. Age-related neuroinflammatory changes negatively impact on neuronal function

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    Marina A Lynch

    2010-01-01

    Full Text Available Neuroinflammatory changes, characterized by an increase in microglial activation and often accompanied by upregulation of inflammatory cytokines like interleukin-1β (IL-1β, are common to many, if not all, neurodegenerative diseases. Similar, though less dramatic neuroinflammatory changes are also known to occur with age. Among the consequences of these changes is an impairment in synaptic function and the evidence suggests that inflammatory cytokines may be the primary contributory factor responsible for the deficits in synaptic plasticity which have been identified in aged rodents. Specifically a decrease in the ability of aged rats to sustain long-term potentiation (LTP in perforant path-granule cells of the hippocampus is associated with increased microglial activation. This review considers the evidence which suggests a causal relationship between these changes and the factors which contribute to the age-related microglial activation, and reflects on data which demonstrate that agents which inhibit microglial activation also improve ability of rats to sustain LTP.

  12. The Chromospheric Activity-Age Relation for M Dwarf Stars

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    Silvestri, N. M.; Oswalt, T. D.; Hawley, S. L.

    2000-12-01

    We present preliminary results from our study in which we use moderate resolution spectroscopy to determine the correlation between the chromospheric activity and age of M dwarf stars in wide binary systems. We have observed ~50 M dwarf stars from our sample with the Apache Point Observatory 3.5-m telescope. We measure the ratio of Hα luminosity to the bolometric luminosity (LHα /Lbol) of the M dwarf---a measure of activity that is proven to correlate well with age. This project is unique in that it will extend the chromospheric activity-age relation of low-mass main sequence stars beyond the ages provided by cluster methods. The ages so determined are also independent of the uncertainties in cluster age determinations. The technique has the potential to improve by at least a factor of two the precision and the range over which ages can currently be determined for main sequence stars. Work on this project is supported by the NASA Graduate Student Researchers Program grant NGT-50290 (N.M.S.).

  13. eNOS-uncoupling in age-related erectile dysfunction

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    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  14. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

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    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  15. Fundus Autofluorescence in Age-related Macular Degeneration

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    Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  16. Age-related changes in the efficacy of crystalloid cardioplegia.

    Science.gov (United States)

    Magovern, J A; Pae, W E; Waldhausen, J A

    1991-09-01

    Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10 degrees C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means +/- standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 +/- 8.2 and 66.2 +/- 7.7%) than in the 6- and 8-week hearts (93.0 +/- 6.4 and 97.6 +/- 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations.

  17. Age-Related Changes in Trabecular Meshwork Imaging

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    Mark E. Gold

    2013-01-01

    Full Text Available Purpose. To evaluate the normal aging effects on trabecular meshwork (TM parameters using Fourier domain anterior segment optical coherence tomography (ASOCT images. Patients and Methods. One eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18–40, 41–60, and 61–80. Measurements were compared using stepwise regression analysis. Results. The average TM parameters were 0.0487 (±0.0092 mm2 for TM area, 0.5502 (±0.1033 mm for TM length, 0.1623 (±0.341 mm2 for TM interface shadow area, and 0.7755 (±0.1574 mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length to 0.82 (TM area. TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters. Conclusion. Although the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function.

  18. Age-related changes in skin topography and microcirculation.

    Science.gov (United States)

    Li, Li; Mac-Mary, Sophie; Marsaut, David; Sainthillier, Jean Marie; Nouveau, Stéphanie; Gharbi, Tijani; de Lacharriere, Olivier; Humbert, Philippe

    2006-03-01

    Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

  19. Ocular Surface Temperature in Age-Related Macular Degeneration

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    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  20. Breed- and age-related differences in canine mammary tumors.

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    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  1. Predicting intentions to consume functional foods and supplements to offset memory loss using an adaptation of protection motivation theory.

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    Cox, D N; Koster, A; Russell, C G

    2004-08-01

    The widespread use of dietary supplements and so-called 'functional foods' is thought to be partially motivated by self-control of health. However, whilst consumers want foods associated with well-being or disease prevention, they are unlikely to be willing to compromise on taste or technology. This presents a dilemma for promoters of functional foods. Middle-aged consumers' intentions to consume functional foods or supplements that may improve memory were tested within an adaptation of Protection Motivation theory (PMT). Participants evaluated text descriptions of four products described as: having an unpleasant bitter taste (Natural-FF); having 'additives' to reduce bitterness (Sweetened-FF); being genetically modified to enhance function (GM-FF) and Supplements. Participants were recruited as being of high and low perceived vulnerability to memory failure. In total, 290 middle-aged consumers (aged 40-60 years) participated in the study. Motivations to consume the GM-FF were the lowest. There were gender differences between intention to consume the supplements, Natural-FF and Sweetened-FF and product differences within genders. Women were less favourable than men in their attitudes towards genetic modification in general. Regression analyses indicated that PM predictors of intention to consume functional foods or supplements explained 59-63% of the variance (R2). Overall, perceived 'efficacy' (of the behaviour) and self-efficacy were the most important predictors of intentions to consume.

  2. A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

    Science.gov (United States)

    Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

    2015-09-01

    A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders.

  3. Update on clinical trials in dry Age-related macular degeneration

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    Ibrahim Taskintuna

    2016-01-01

    Full Text Available This review article summarizes the most recent clinical trials for dry age.related macular degeneration (AMD, the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age.Related Eye Disease Study 2 (AREDS2, implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  4. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    Science.gov (United States)

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  5. An overview on age related macular degeneration and recent advances in its management

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    SOBIA N.

    2014-03-01

    Full Text Available Age-related macular degeneration (AMD is a condition characterized, in the early stages, by slow development and progression, absence of symptoms over a number of years, and extensive retinal deposits called drusen, often associated with pigmentary abnormalities (early AMD.There is strong and consistent evidence that increasing age, family history, obesity/high body mass index, and cataract surgery are associated with late AMD. Smoking is the strongest and most consistently found modifiable risk factor for late AMD.Age-related macular degeneration remains one of the most severe and profound disabilities encountered in medicine, particularly due to the loss of the central vision and the high economic burden it places on patients and societies.Recent advances in management of AMD is anti-angiogenic drugs. The identification of the crucial role played by vascular endothelial growth factor (VEGF in the pathogenesis of wet AMD hasallowed the development of VEGF-blocking agents such as bevacizumab, pegaptanib and ranibizumab.

  6. Loss of attentional inhibition in older adults--Does it really exist? An experimental dissociation of inhibitory and memory retrieval processes.

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    Giesen, Carina; Eberhard, Maike; Rothermund, Klaus

    2015-06-01

    It is commonly assumed that attentional inhibitory functioning decreases with age, even though empirical evidence is mixed. These inconsistencies possibly stem from methodological artifacts: distractor inhibition is typically assessed with the negative priming paradigm, which confounds inhibition and episodic retrieval. In the present study, we investigated age differences in a sequential distractor repetition paradigm (Giesen, Frings, & Rothermund, 2012) that provides independent estimates of distractor inhibition and episodic retrieval processes. Older (60+ yrs) and younger (below 30 years) adults identified target letters that were flanked by distractors (JKJ). Inhibitory processes were preserved in older adults, who showed reliable distractor repetition benefits resulting from persistent distractor inhibition; however, a significant loss of inhibition was apparent for the older subgroup of participants (65+ yrs) compared with a subgroup of young-old participants (60 to 64 years). No age differences were found for episodic retrieval processes of stimulus-response bindings that were indexed by an interaction of distractor repetition and response relation. Findings highlight the importance of dissociating between distractor inhibition and retrieval processes that are differently implicated in age-related cognitive change.

  7. Age-related increases in false recognition: The role of perceptual and conceptual similarity

    Directory of Open Access Journals (Sweden)

    Laura M. Pidgeon

    2014-10-01

    Full Text Available Older adults are more likely to falsely recognize novel events than young adults, and recent behavioral and neuroimaging evidence points to a reduced ability to distinguish overlapping information due to decline in hippocampal pattern separation. However, other data suggest a critical role for semantic similarity. Koutstaal et al. [(2003. False recognition of abstract versus common objects in older and younger adults: Testing the semantic categorization account, J. Exp Psychol. Learn, 29(4, 499-510] reported that older adults were only vulnerable to false recognition of items with pre-existing semantic representations. We replicated Koutstaal et al.’s (2003 second experiment and examined the influence of independently rated perceptual and conceptual similarity between stimuli and lures. At study, young and older adults judged the pleasantness of pictures of abstract (unfamiliar and concrete (familiar items, followed by a surprise recognition test including studied items, similar lures, and novel unrelated items. Experiment 1 used dichotomous ‘old/new’ responses at test, while in Experiment 2 participants were also asked to judge lures as ‘similar’, to increase explicit demands on pattern separation. In both experiments, older adults showed a greater increase in false recognition for concrete than abstract items relative to the young, replicating Koutstaal et al.’s (2003 findings. However, unlike in the earlier study, there was also an age-related increase in false recognition of abstract lures when multiple similar images had been studied. In line with pattern separation accounts of false recognition, older adults were more likely to misclassify concrete lures with high and moderate, but not low degrees of rated similarity to studied items. Results are consistent with the view that older adults are particularly susceptible to semantic interference in recognition memory, and with the possibility that this reflects age-related decline

  8. Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2010-05-01

    Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

  9. Age-related declines in distortion product otoacoustic emissions utilizing pure tone contralateral stimulation in CBA/CaJ mice.

    Science.gov (United States)

    Varghese, George I; Zhu, Xiaoxia; Frisina, Robert D

    2005-11-01

    One role of the medial olivocochlear (MOC) auditory efferent system is to suppress cochlear outer hair cell (OHC) responses when presented with a contralateral sound. Using distortion product otoacoustic emissions (DPOAEs), the effects of active changes in OHC responses due to the MOC as a function of age can be observed when contralateral stimulation with a pure tone is applied. Previous studies have shown that there are age-related declines of the MOC when broad band noise is presented to the contralateral ear. In this study, we measured age-related changes in CBA/CaJ mice by comparing DPOAE generation with and without a contralateral pure tone at three different frequencies (12, 22, and 37 kHz). Young (n = 16), middle (n = 10) and old-aged (n = 10) CBA mice were tested. DPOAE-grams were obtained using L1 = 65 and L2 = 50 dB SPL, F1/F2 = 1.25, using eight points per octave covering a frequency range from 5.6-44.8 kHz. The pure tone was presented contralaterally at 55 dB SPL. DPOAE-grams and ABR levels indicated age-related hearing loss in the old mice. In addition, there was an overall change in DPOAEs in the middle-aged and old groups relative to the young. Pure tone stimulation was not as effective as a suppressor compared to broadband noise. An increase in pure tone frequency from 12 to 22 kHz induced greater suppression of DPOAEs, but the 37 kHz was least effective. These results indicate that as the mouse ages, there are significant changes in the efficiency of the suppression mechanism as elicited by contralateral narrowband stimuli. These findings reinforce the idea that age-related changes in the MOC or the operating points of OHCs play a role in the progression of presbycusis - age-related hearing loss in mammals.

  10. Loss of cyclin-dependent kinase 5 from parvalbumin interneurons leads to hyperinhibition, decreased anxiety, and memory impairment.

    Science.gov (United States)

    Rudenko, Andrii; Seo, Jinsoo; Hu, Ji; Su, Susan C; de Anda, Froylan Calderon; Durak, Omer; Ericsson, Maria; Carlén, Marie; Tsai, Li-Huei

    2015-02-11

    Perturbations in fast-spiking parvalbumin (PV) interneurons are hypothesized to be a major component of various neuropsychiatric disorders; however, the mechanisms regulating PV interneurons remain mostly unknown. Recently, cyclin-dependent kinase 5 (Cdk5) has been shown to function as a major regulator of synaptic plasticity. Here, we demonstrate that genetic ablation of Cdk5 in PV interneurons in mouse brain leads to an increase in GABAergic neurotransmission and impaired synaptic plasticity. PVCre;fCdk5 mice display a range of behavioral abnormalities, including decreased anxiety and memory impairment. Our results reveal a central role of Cdk5 expressed in PV interneurons in gating inhibitory neurotransmission and underscore the importance of such regulation during behavioral tasks. Our findings suggest that Cdk5 can be considered a promising therapeutic target in a variety of conditions attributed to inhibitory interneuronal dysfunction, such as epilepsy, anxiety disorders, and schizophrenia.

  11. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

    Science.gov (United States)

    Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  12. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  13. Age-related decline in global form suppression.

    Science.gov (United States)

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution.

  14. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  15. The burden of age-related macular degeneration.

    Science.gov (United States)

    Schmier, Jordana K; Jones, Mechelle L; Halpern, Michael T

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

  16. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  17. Systemic complement activation in age-related macular degeneration.

    Science.gov (United States)

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (pAMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  18. Age related macular degeneration and drusen: neuroinflammation in the retina.

    Science.gov (United States)

    Buschini, Elisa; Piras, Antonio; Nuzzi, Raffaele; Vercelli, Alessandro

    2011-09-15

    Inflammation protects from dangerous stimuli, restoring normal tissue homeostasis. Inflammatory response in the nervous system ("neuroinflammation") has distinct features, which are shared in several diseases. The retina is an immune-privileged site, and the tight balance of immune reaction can be disrupted and lead to age-related macular disease (AMD) and to its peculiar sign, the druse. Excessive activation of inflammatory and immunological cascade with subsequent induction of damage, persistent activation of resident immune cells, accumulation of byproducts that exceeds the normal capacity of clearance giving origin to a chronic local inflammation, alterations in the activation of the complement system, infiltration of macrophages, T-lymphocytes and mast-cells from the bloodstream, participate in the mechanisms which originate the drusen. In addition, aging of the retina and AMD involve also para-inflammation, by which immune cells react to persistent stressful stimuli generating low-grade inflammation, aimed at restoring function and maintaining tissue homeostasis by varying the set point in relation to the new altered conditions. This mechanism is also seen in the normal aging retina, but, in the presence of noxious stimuli as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy may provide new insights to understand AMD pathology, due to its contribution in the removal of defective proteins. Therefore, the AMD retina can represent a valuable model to study neuroinflammation, its mechanisms and therapy in a restricted and controllable environment. Targeting these pathways could represent a new way to treat and prevent both exudative and dry forms of AMD.

  19. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  20. Nutrition in the age-related disablement process

    NARCIS (Netherlands)

    Inzitari, M.; Doets, E.L.; Bartali, B.; Bari, Di M.; Visser, M.; Volpato, S.; Gambassi, G.; Topinkova, E.; Groot, de C.P.G.M.; Salva, A.

    2011-01-01

    The transition from independence to disability in older adults is characterized by detectable changes in body composition and physical function. Epidemiologic studies have shown that weight loss, reduced caloric intake and the reduced intake of specific nutrients are associated with such changes. Th

  1. Neural correlates of age-related decline and compensation in visual attention capacity

    DEFF Research Database (Denmark)

    Wiegand, Iris; Töllner, Thomas; Dyrholm, Mads

    2014-01-01

    -individual differences in K. Moreover, both parameters were selectively related to two further ERP waves in older age: The anterior N1 was reduced for older participants with lower processing speed, indicating that age-related loss of attentional resources slows encoding. An enhanced right-central positivity (RCP......We identified neural correlates of declined and preserved basic visual attention functions in aging individuals based on Bundesen’s ‘Theory of Visual Attention’ (TVA). In an inter-individual difference approach, we contrasted electrophysiology of higher- and lower-performing younger and older......) was found only for older participants with high storage capacity, suggesting compensatory recruitment for retaining vSTM performance. Together, our results demonstrate that attentional capacity in older age depends on both preservation and successful reorganization of the underlying brain circuits...

  2. New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Verma Lalit

    2000-01-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

  3. Genetics of immunological and inflammatory components in age-related macular degeneration.

    Science.gov (United States)

    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-02-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD.

  4. Autophagy regulating kinases as potential therapeutic targets for age-related macular degeneration.

    Science.gov (United States)

    Kaarniranta, Kai; Kauppinen, Anu; Blasiak, Janusz; Salminen, Antero

    2012-11-01

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly in the developed countries. The number of AMD patients will double during the next decades due to increasing number of aged people. Chronic oxidative stress, inflammation and accumulation of protein-rich deposits both in the retinal pigment epithelium lysosomes and under the retinal pigment epithelium herald the onset of AMD. The disease can be divided into dry and wet AMD forms. The dry form of the disease is more prevalent accounting for up to 90% of all cases. Continued intraocular injections are the current treatment strategy to prevent progression of wet AMD. It is a major challenge to develop new drugs that could prevent or at least ease the symptoms of the increasing population of AMD patients. Since AMD pathology is clearly associated with accumulated protein deposits, the autophagy clearance system might represent a potential future therapeutic target for AMD as is thoroughly discussed here.

  5. Estrogen signalling in the pathogenesis of age-related macular degeneration.

    Science.gov (United States)

    Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

    2015-02-01

    Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

  6. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    Science.gov (United States)

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  7. Physical activity patterns in patients with early and late age-related macular degeneration

    DEFF Research Database (Denmark)

    Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    best-corrected visual acuity in the best-seeing and the worse-seeing eye was associated with less engagement in physical activities that would work up sweat and a lower number of steps taken daily. Patients with bilateral vision loss from late AMD engaged in physical activities that were more......INTRODUCTION: Age-related macular degeneration (AMD) leads to visual impairment that affects visual functioning and thereby the ability to be physically active. We investigated physical activity patterns in patients with AMD. METHODS: Patients with early and late AMD and elderly controls were...... recruited for this hospital-based cross-sectional study. All participants had their best-corrected visual acuity measured and were interviewed about their physical activity based on questions that covered regular physical activity, physical activity that would work up sweat, climbing the stairs and time...

  8. Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Alzheimer's disease (AD and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

  9. Young child with severe brain volume loss easily passes the word memory test and medical symptom validity test: implications for mild TBI.

    Science.gov (United States)

    Carone, Dominic A

    2014-01-01

    The Word Memory Test (WMT) and Medical Symptom Validity Test (MSVT) are two commonly used free-standing measures of test-taking effort. The use of any test as a measure of effort is enhanced when evidence shows that it can be easily passed by patients with severe neurological conditions. The opportunity arose to administer the WMT and MSVT to a 9-year-old girl (referred to as CJ) with severe congenital bilateral brain tissue loss (shown via a compelling brain MRI image), chronic epilepsy, an extremely low Full Scale IQ, extremely low adaptive functioning, developmental delays, numerous severe cognitive impairments, and treatment with multiple high-dose benzodiazepines. She received extensive early intervention services and numerous academic accommodations. Despite this set of problems, CJ passed the WMT and MSVT at perfect to near perfect levels. Implications for failure on these tests among patients with known or alleged mild traumatic brain injury are discussed.

  10. Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice

    Directory of Open Access Journals (Sweden)

    Dustin H Brewton

    2016-11-01

    Full Text Available Age-related changes in inhibitory neurotransmission in sensory cortex may underlie deficits in sensory function. Perineuronal nets (PNNs are extracellular matrix components that ensheath some inhibitory neurons, particularly parvalbumin positive (PV+ interneurons. PNNs may protect PV+ cells from oxidative stress and help establish their rapid spiking properties. Although PNN expression has been well characterized during development, possible changes in aging sensory cortex have not been investigated. Here we tested the hypothesis that PNN+, PV+ and PV/PNN co-localized cell densities decline with age in the primary auditory cortex (A1. This hypothesis was tested using immunohistochemistry in two strains of mice (C57BL/6 and CBA/CaJ with different susceptibility to age-related hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old. We report that PNN+ and PV/PNN co-localized cell densities decline significantly with age in A1 in both mouse strains. In the PNN+ cells that remain in the old group, the intensity of PNN staining is reduced in the C57 strain, but not the CBA strain. PV+ cell density also declines only in the C57, but not the CBA, mouse suggesting a potential exacerbation of age-effects by hearing loss in the PV/PNN system. Taken together, these data suggest that PNN deterioration may be a key component of altered inhibition in the aging sensory cortex, that may lead to altered synaptic function, susceptibility to oxidative stress and processing deficits.

  11. Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration.

    Science.gov (United States)

    Katz, Martin L

    2002-01-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in developed countries. The vision loss associated with AMD is the result of degenerative changes in the central region of the retina called the macula. Maintenance of normal structure and function of the macular retina, and of the remainder of the retina as well, is critically dependent on the supporting role of the adjacent retinal pigment epithelium (RPE). Impairment of normal RPE functions is known to result in retinal degeneration and loss of visual function. Thus, it has been hypothesized that the retinal degeneration that characterizes AMD is secondary to age-related deterioration in RPE support functions. Like many other postmitotic cell types, the RPE accumulates autofluorescent lysosomal storage bodies (lipofuscin) during senescence. In human eyes, lipofuscin comes to occupy a substantial fraction of the RPE cytoplasmic volume in the elderly. Does this lipofuscin accumulation contribute to the development of AMD? This question is a specific case of the broader question of whether lipofuscin accumulation in general is detrimental to cells. Unfortunately, definitive data do not exist to allow these questions to be answered. Although a correlation between RPE lipofuscin content and AMD has been reported, a cause-and-effect relationship between RPE lipofuscin accumulation and the development of this disease has not been established. It has been reported that a mutation in a gene encoding a photoreceptor-specific protein results in massive RPE lipofuscin accumulation and early-onset macular degeneration. However, again the accelerated RPE lipofuscin accumulation has not been shown to be the cause of the accompanying macular degeneration. The lack of a definitive link between RPE lipofuscin accumulation and AMD illustrates one of the biggest challenges remaining in lipofuscin research-determining whether lipofuscin accumulation per se has an impact on cell function.

  12. Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Silène T Wavre-Shapton

    Full Text Available The retinal pigment epithelium (RPE is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1. REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox, Tyr-Cre+. Transmission electron microscopy (TEM was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox, Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

  13. Profile of ranibizumab: efficacy and safety for the treatment of wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Chen Y

    2012-07-01

    Full Text Available Youxin Chen, Fei HanDepartment of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaAbstract: Wet age-related macular degeneration (AMD causes severe vision loss due to the development of choroidal neovascularization (CNV. The critical role of vascular endothelial growth factor in the pathogenesis of CNV is well understood. Ranibizumab plays an inhibitory role with CNV and reduces vascular permeability by binding to vascular endothelial growth factor. Intravitreal ranibizumab reduces the risk of visual acuity (VA loss and increases the chance of VA gain compared with no treatment or photodynamic therapy for CNV in AMD. Some high-quality research has shown that the optimal timing for ranibizumab treating wet AMD is the first 3 months. It is recommended that ranibizumab is intravitreally injected monthly in the initiation for at least 3 months. Subsequent managing of regimens should be made dependent on the VA change, fundus examination, and image of optical coherence topography. An individualized strategy or combined method with photodynamic therapy is beneficial to the active lesion in the consecutive treatment of ranibizumab for CNV, and may be a good choice in order to decrease injection times. Regarding the safety profile, ranibizumab has been well tolerated in clinical trials. The principal ocular adverse event detected in clinical trials is a low frequency of ocular inflammation. Key serious ocular adverse events occurred in <5% of ranibizumab-treated patients in large-scale clinical trials. It appears unlikely that treatment with ranibizumab increases the risk of vascular events significantly. Less frequent injections on an as-needed schedule, based on monthly monitoring may have the most optimal risk:benefit ratio.Keywords: age-related macular degeneration, choroidal neovascularization, ranibizumab, efficacy, safety

  14. Association of Chronic Obstructive Pulmonary Disease With Increased Confusion or Memory Loss and Functional Limitations Among Adults in 21 States, 2011 Behavioral Risk Factor Surveillance System

    Directory of Open Access Journals (Sweden)

    Kurt J. Greenlund, PhD

    2016-01-01

    Full Text Available Introduction Chronic obstructive pulmonary disease (COPD is associated with cognitive impairment, but consequences of this association on a person’s functional limitations are unclear. We examined the association between COPD and increased confusion and memory loss (ICML and functional limitations among adults with COPD. Methods We studied adults aged 45 years or older in 21 states who participated in the 2011 Behavioral Risk Factor Surveillance System (n = 102,739. Presence of COPD was based on self-reported physician diagnosis. ICML was based on self-report that confusion or memory loss occurred more often or worsened during the prior year. ICML-associated difficulties were defined as giving up household chores and former activities, decreased ability to work or engage in social activities, or needing help from family or friends during the prior year due to ICML. General limitations were defined as needing special equipment as a result of a health condition, having had activity limitations for 2 weeks or more in the prior month, or being unable to work. Multivariable models were adjusted for demographics, health behaviors or conditions, and frequent mental distress. Results COPD was reported by 9.3% of adults. ICML was greater among those with COPD than among those without COPD (25.8% vs 11%; adjusted prevalence ratio [aPR], 1.48; 95% confidence interval [CI], 1.32%–1.66%. People with COPD, either with or without ICML, were more likely than those without COPD to report general functional limitations. Among people reporting ICML, those with COPD were more likely to report interference with work or social activities than those without COPD (aPR, 1.17; 95% CI, 1.01%–1.36%. Conclusion Functional limitations were greater among those with COPD than among those without, and ICML may further affect these limitations. Results from our study can inform future studies of self- management and functional limitations for people with COPD.

  15. Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.

    Science.gov (United States)

    Kobayashi, Keiji; Nojiri, Hidetoshi; Saita, Yoshitomo; Morikawa, Daichi; Ozawa, Yusuke; Watanabe, Kenji; Koike, Masato; Asou, Yoshinori; Shirasawa, Takuji; Yokote, Koutaro; Kaneko, Kazuo; Shimizu, Takahiko

    2015-03-16

    Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to bone tissue. The number of living osteocytes and canalicular networks declines in an age-dependent manner. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated mice lacking mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Like an aged bone, Sod2 depletion in the osteocytes positively enhanced the production of cellular superoxide in vivo. A bone morphological analysis demonstrated that the Sod2-deficient femurs showed remarkable bone loss in an age-dependent manner. Interestingly, Sod2 loss induced markedly disorganized osteocytic canalicular networks and decreased the number of live osteocytes. Furthermore, Sod2 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-κB ligand (RANKL). In vitro experiments also revealed that treatment with paraquat, a superoxide inducer in mitochondria, promoted the RANKL expression via, in part, ERK phosphorylation. These findings demonstrate that the mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age-related bone loss due to the impairment of canalicular networks and bone metabolism via the deregulation of the sclerostin and RANKL expression.

  16. Age-related differences in adaptive decision making

    Directory of Open Access Journals (Sweden)

    Irwin P. Levin

    2007-08-01

    Full Text Available While previous research has found that children make more risky decisions than their parents, little is known about the developmental trajectory for the ability to make advantageous decisions. In a sample of children, 5--11 years old, we administered a new risky decision making task in which the relative expected value (EV of the risky and riskless choice options was varied over trials. Younger children (age 5--7 showed significantly less responsiveness to EV differences than their parents on both trials involving risky gains and trials involving risky losses. For older children (age 8--11 this deficit was smaller overall but was greater on loss trials than on gain trials. Children of both ages made more risky choices than adults when risky choices were disadvantageous. We further analyzed these results in terms of children's ability to utilize probability and outcome information, and discussed them in terms of developing brain structures vital for decision making under uncertainty.

  17. The role of education and verbal abilities in altering the effect of age-related gray matter differences on cognition.

    Directory of Open Access Journals (Sweden)

    Jason Steffener

    Full Text Available Evidence suggests that individual variability in lifetime exposures influences how cognitive performance changes with advancing age. Brain maintenance and cognitive reserve are theories meant to account for preserved performance despite advancing age. These theories differ in their causal mechanisms. Brain maintenance predicts more advantageous lifetime exposures will reduce age-related neural differences. Cognitive reserve predicts that lifetime exposures will not directly reduce these differences but minimize their impact on cognitive performance. The present work used moderated-mediation modeling to investigate the contributions of these mechanisms at explaining variability in cognitive performance among a group of 39 healthy younger (mean age (standard deviation 25.9 (2.92 and 45 healthy older adults (65.2 (2.79. Cognitive scores were computed using composite measures from three separate domains (speed of processing, fluid reasoning, and memory, while their lifetime exposures were estimated using education and verbal IQ measures. T1-weighted MR images were used to measure cortical thickness and subcortical volumes. Results suggest a stronger role for cognitive reserve mechanisms in explaining age-related cognitive variability: even with age-related reduced gray matter, individuals with greater lifetime exposures could perform better given their quantity of brain measures.

  18. Loss of multi-epitope specificity in memory CD4(+ T cell responses to B. pertussis with age.

    Directory of Open Access Journals (Sweden)

    Wanda G H Han

    Full Text Available Pertussis is still occurring in highly vaccinated populations, affecting individuals of all ages. Long-lived Th1 CD4(+ T cells are essential for protective immunity against pertussis. For better understanding of the limited immunological memory to Bordetella pertussis, we used a panel of Pertactin and Pertussis toxin specific peptides to interrogate CD4(+ T cell responses at the epitope level in a unique cohort of symptomatic pertussis patients of different ages, at various time intervals after infection. Our study showed that pertussis epitope-specific T cell responses contained Th1 and Th2 components irrespective of the epitope studied, time after infection, or age. In contrast, the breadth of the pertussis-directed CD4(+ T cell response seemed dependent on age and closeness to infection. Multi-epitope specificity long-term after infection was lost in older age groups. Detailed knowledge on pertussis specific immune mechanisms and their insufficiencies is important for understanding resurgence of pertussis in highly vaccinated populations.

  19. Vision rehabilitation for age-related macular degeneration.

    Science.gov (United States)

    Park, W

    1999-01-01

    Though the numbers of patients with ARMD are high, associated referrals for vision rehabilitation are not. Practitioners need to refer patients with age-related maculopathy when medical and surgical treatment are no longer possible, and patients need to be educated to that fact. The impact of improving activities of daily living may be monumental and benefits society as a whole. People who are visually impaired are often ill-prepared to deal with the substantial adjustment involved, further stressing their entire support system. It may not be safe for visual and systemic reasons for older adults to cook, clean, and maintain their home. Poor vision contributes to the already increased risk of falls and subsequent fractures in these patients. Individuals who may have already been told they can no longer drive now face the possibility of being unable to live in their houses. Their independence may be threatened dramatically and abruptly. All these circumstances contribute to anxiety and depression. Patients with ARMD need to be educated about their disease process (teaching that can never be assumed to have been initiated). They need to be educated that they will not go completely blind and that, with assistance, they can accomplish a great deal. With today's technology, it is not difficult to help visually impaired individuals with ARMD, unless they are not referred or lack motivation. The primary complaint of an individual with ARMD is recognition of central detail. This affects all activities of daily living, and patient performance is subject to the duration and severity of the disease (including the size, density, and location of the central scotoma) and to their understanding of the disease. Rubin and coworkers, found that slow reading performance of patients with a dense central scotoma might reflect inherent limitations of peripheral retina for complex visual tasks. ARMD in most cases lends itself to magnification that enlarges the object beyond the blind spot

  20. Age-related cognitive decline during normal aging: the complex effect of education.

    Science.gov (United States)

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain.

  1. Deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for Alzheimer's disease by deep sequencing.

    Science.gov (United States)

    Bouter, Yvonne; Kacprowski, Tim; Weissmann, Robert; Dietrich, Katharina; Borgers, Henning; Brauß, Andreas; Sperling, Christian; Wirths, Oliver; Albrecht, Mario; Jensen, Lars R; Kuss, Andreas W; Bayer, Thomas A

    2014-01-01

    One of the central research questions on the etiology of Alzheimer's disease (AD) is the elucidation of the molecular signatures triggered by the amyloid cascade of pathological events. Next-generation sequencing allows the identification of genes involved in disease processes in an unbiased manner. We have combined this technique with the analysis of two AD mouse models: (1) The 5XFAD model develops early plaque formation, intraneuronal Aβ aggregation, neuron loss, and behavioral deficits. (2) The Tg4-42 model expresses N-truncated Aβ4-42 and develops neuron loss and behavioral deficits albeit without plaque formation. Our results show that learning and memory deficits in the Morris water maze and fear conditioning tasks in Tg4-42 mice at 12 months of age are similar to the deficits in 5XFAD animals. This suggested that comparative gene expression analysis between the models would allow the dissection of plaque-related and -unrelated disease relevant factors. Using deep sequencing differentially expressed genes (DEGs) were identified and subsequently verified by quantitative PCR. Nineteen DEGs were identified in pre-symptomatic young 5XFAD mice, and none in young Tg4-42 mice. In the aged cohort, 131 DEGs were found in 5XFAD and 56 DEGs in Tg4-42 mice. Many of the DEGs specific to the 5XFAD model belong to neuroinflammatory processes typically associated with plaques. Interestingly, 36 DEGs were identified in both mouse models indicating common disease pathways associated with behavioral deficits and neuron loss.

  2. Age-related deficits in selective attention during encoding increase demands on episodic reconstruction during context retrieval: An ERP study

    Science.gov (United States)

    James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey

    2017-01-01

    Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object’s relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. PMID:27094851

  3. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD...... a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  4. Current and emerging therapies for the treatment of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    M Vaughn Emerson

    2008-06-01

    Full Text Available M Vaughn Emerson, Andreas K LauerCasey Eye Institute, Oregon Health and Science University, Portland, OR, USAAbstract: Age-related macular degeneration (AMD is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary

  5. Age-related alterations in the neural coding of envelope periodicities.

    Science.gov (United States)

    Walton, Joseph P; Simon, Henry; Frisina, Robert D

    2002-08-01

    . The magnitude of the differences between the young adult and the old spike median responses was greatest at low MFs and then declined as MF increased. Finally, the young adult distribution of rBMFs extends to higher MFs than the old, with 36.0% of units having rBMFs >100 Hz as compared with only 12.5% of the old unit sample. We postulate that this age-related difference in rate coding of SAM noise carriers is consistent with a loss, or imbalance, of excitatory and inhibitory neural mechanisms known to shape encoding of envelope periodicities in the IC.

  6. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    Science.gov (United States)

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  7. Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

    Institute of Scientific and Technical Information of China (English)

    Hongkai Wang; Chengren Li; Hanzhi Wang; Feng Mei; Zhi Liu; Hai-Ying Shen; Lan Xiao

    2013-01-01

    Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined.Recently,accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis.We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia.In the present study,three different age cohorts of mice,i.e.juvenile (3 weeks),young-adult (6 weeks) and middle-aged (8months),were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination.Then,age-related vulnerability to CPZ-induced demyelination,behavioral outcomes,and myelination-related molecular biological changes were assessed.We demonstrated:(1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum,a region closely associated with the pathophysiology of schizophrenia; (2)the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein,more loss of CC-1-positive mature oligodendrocytes,and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice.Together,our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit,providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

  8. Age-related changes in midbrain dopaminergic regulation of the human reward system

    Science.gov (United States)

    Dreher, Jean-Claude; Meyer-Lindenberg, Andreas; Kohn, Philip; Berman, Karen Faith

    2008-01-01

    The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and reward-related neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[18F]FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging. PMID:18794529

  9. Age-related macular degeneration--emerging pathogenetic and therapeutic concepts.

    Science.gov (United States)

    Gehrs, Karen M; Anderson, Don H; Johnson, Lincoln V; Hageman, Gregory S

    2006-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene--which encodes the major inhibitor of the complement alternative pathway--is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel

  10. Cost-effectiveness of smoking cessation to prevent age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Matthews Jane P

    2008-09-01

    Full Text Available Abstract Background Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. Methods We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes for 1,000 randomly selected U.S. smokers. We used a computer simulation model to predict the incidence of macular degeneration and blindness, the number of quality-adjusted life-years (QALYs, and direct costs (in 2004 U.S. dollars until age 85 years. Cost-effectiveness ratios were based on the cost of the Massachusetts Tobacco Control Program. Costs and QALYs were discounted at 3% per year. Results If 1,000 smokers quit, our model predicted 48 fewer cases of macular degeneration, 12 fewer cases of blindness, and a gain of 1,600 QALYs. Macular degeneration-related costs would decrease by $2.5 million if the costs of caregivers for people with vision loss were included, or by $1.1 million if caregiver costs were excluded. At a cost of $1,400 per quitter, smoking cessation was cost-saving when caregiver costs were included, and cost about $200 per QALY gained when caregiver costs were excluded. Sensitivity analyses had a negligible impact. The cost per quitter would have to exceed $77,000 for the cost per QALY for smoking cessation to reach $50,000, a threshold above which interventions are sometimes viewed as not cost-effective. Conclusion Smoking cessation is unequivocally cost-effective in terms of its impact on age-related macular degeneration outcomes alone.

  11. Ranibizumab: the evidence of its therapeutic value in neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Peter K. Kaiser

    2008-07-01

    Full Text Available Peter K. KaiserCole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USAIntroduction: Neovascular age-related macular degeneration (AMD is the leading cause of severe, irreversible visual impairment in people over 60 years of age. Neovascular AMD is characterized by abnormal growth of blood vessels under the retina, specifically the macula. These vessels leak blood and fluids, damaging the retina and its photoreceptors, resulting in permanent loss of central vision. Vascular endothelial growth factor-A (VEGF-A has been shown to play a critical role in the pathogenesis of neovascular AMD. In the US, ranibizumab, a VEGF-A blocker, is approved and indicated for the treatment of patients with neovascular AMD.Aims: To review the clinical evidence for ranibizumab in the treatment of neovascular AMD.Evidence review: Phase III clinical trial data have established ranibizumab as a safe and well-tolerated treatment for neovascular AMD. Monthly intravitreal injections of ranibizumab result in a statistically significantly greater proportion of patients losing <15 letters of visual acuity (VA and statistically significant increases in the mean number of letters gained compared with controls. Anatomically, ranibizumab results in stabilization in the mean area of choroidal neovascularization (CNV and statistically significant reductions in the mean area of leakage compared with controls. Although there is limited economic evidence available, ranibizumab therapy for neovascular AMD appears to deliver a significant degree of value gain in terms of quality of life when compared with other neovascular AMD interventions.Place in therapy: Clinical evidence establishes ranibizumab as a first-line therapy option for virtually all treatable neovascular AMD patients. Updating neovascular AMD treatment guidelines to reflect the evidence base for ranibizumab as a preferred first-line therapy would be beneficial for physicians in making informed treatment

  12. Pegaptanib sodium for neovascular age-related macular degeneration: clinical experience in the UK

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    Sobha Sivaprasad

    2008-06-01

    Full Text Available Sobha Sivaprasad, Nachiketa Acharya, Phil HykinMoorfields Eye Hospital, London, UKAbstract: The pathogenesis of age-related macular degeneration (AMD is unclear, but it can take either a neovascular/exudative/wet form, characterized by choroidal neovascularization (CNV, or a dry form. No treatments are available for the dry form, but there are a number of pharmacological interventions that inhibit vascular endothelial growth factor (VEGF, which is central to the pathogenesis of CNV and neovascular AMD. Available anti-VEGF agents either target all active VEGF isoforms (eg, ranibizumab, or take a more selective approach and inhibit only VEGF165 (eg, pegaptantib sodium. Current guidance on their use is equivocal and restrictive at best, resulting in associated difficulties in securing adequate, timely funding for treatment. The Moorfields Eye Hospital undertook an audit of 70 patients receiving intravitreal (ITV pegaptanib sodium on a pro re nata (prn dosing schedule. Despite initial funding delays, the audit recorded superior treatment outcomes compared with those reported in the VISION trials at 12 weeks: 88% of audit patients maintained stable vision, 29% gained vision and 6% experienced severe vision loss compared with 70%, ≥6% and ≤10% of patients in VISION at 54 weeks, respectively. The audit indicates a positive correlation between patients with better baseline visual acuity (VA and improved therapeutic benefits, including a greater likelihood of both vision gain and vision preservation. Experience at Moorfields also suggests that pegaptanib sodium is more useful in occult lesions than minimally classic lesions, and clinical experience suggests that combination therapies may offer the best approach with anti-VEGF therapies. Further randomized clinical trials will help better determine the optimal treatment strategies with pegaptanib sodium in neovascular AMD.Keywords: age-related macular degeneration, choroidal neovascularization

  13. Chronic GluN2B antagonism disrupts behavior in wild-type mice without protecting against synapse loss or memory impairment in Alzheimer's disease mouse models.

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    Hanson, Jesse E; Meilandt, William J; Gogineni, Alvin; Reynen, Paul; Herrington, James; Weimer, Robby M; Scearce-Levie, Kimberly; Zhou, Qiang

    2014-06-11

    Extensive evidence implicates GluN2B-containing NMDA receptors (GluN2B-NMDARs) in excitotoxic-insult-induced neurodegeneration and amyloid β (Aβ)-induced synaptic dysfunction. Therefore, inhibiting GluN2B-NMDARs would appear to be a potential therapeutic strategy to provide neuroprotection and improve cognitive function in Alzheimer's disease (AD). However, there are no reports of long-term in vivo treatment of AD mouse models with GluN2B antagonists. We used piperidine18 (Pip18), a potent and selective GluN2B-NMDAR antagonist with favorable pharmacokinetic properties, for long-term dosing in AD mouse models. Reduced freezing behavior in Tg2576 mice during fear conditioning was partially reversed after subchronic (17 d) Pip18 treatment. However, analysis of freezing behavior in different contexts indicated that this increased freezing likely involves elevated anxiety or excessive memory generalization in both nontransgenic (NTG) and Tg2576 mice. In PS2APP mice chronically fed with medicated food containing Pip18 for 4 months, spatial learning and memory deficits were not rescued, plaque-associated spine loss was not affected, and synaptic function was not altered. At the same time, altered open field activity consistent with increased anxiety and degraded performance in an active avoidance task were observed in NTG after chronic treatment. These results indicate that long-term treatment with a GluN2B-NMDAR antagonist does not provide a disease-modifying benefit and could cause cognitive liabilities rather than symptomatic benefit in AD mouse models. Therefore, these results challenge the expectation of the therapeutic potential for GluN2B-NMDAR antagonists in AD.

  14. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  15. Management of Neovascular Age-related Macular Degeneration: A Review on Landmark Randomized Controlled Trials.

    Science.gov (United States)

    Agarwal, Aniruddha; Aggarwal, Kanika; Gupta, Vishali

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti-vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground-breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

  16. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Aniruddha Agarwal

    2016-01-01

    Full Text Available In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age.related macular degeneration (AMD. These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have led to substantial improvements in the outcome of these patients. The introduction of anti.vascular endothelial growth factor agents has resulted in improvement of visual outcomes and has had a positive impact on the quality of life among elderly population. While the contemporary management of neovascular AMD has been successful in tremendously reducing the visual morbidity, the financial burden of therapy has increased exponentially. To overcome these challenges, newer pharmacologic agents are evaluated for their efficacy and safety in AMD. Ground.breaking advances in bench to bedside research have led to discovery of new pathways that appear to be viable targets for preventing visual loss in AMD. In this review, study designs and results of landmark clinical trials in AMD from the past decade have been summarized.

  17. Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage

    Institute of Scientific and Technical Information of China (English)

    Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He

    2014-01-01

    The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and

  18. Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

    Science.gov (United States)

    Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H

    2015-12-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

  19. 术中失血量对手术患者记忆障碍的影响及护理对策%Influence of blood loss during operation on postoperative memory disorders: nursing countermeasure

    Institute of Scientific and Technical Information of China (English)

    张新华; 雷鹏琼; 陈长香; 姚美

    2012-01-01

    Objective To explore the incidence and the influence of blood loss during operation on postoperative memory disorders. Methods The amount of blood loss during operation in 282 surgical patients was obtained by weighing and measuring. Their memory functions were assessed with the Rivermead Behavior Memory Test II (RBMT-TJ ) 24 hours before and after operation. Results Of the 282 patients, 194(68. 8%) had memory disorders> with mild, moderate and severe memory disorders making up 50. 5%, 47. 9% , and 1.6% respectively. Those with intraoperative blood loss more than 400 mL had high rate of memory disorders which were severer (P<0. 01). Conclusion Blood loss during operation has an impact on memory function of post-operative patients. Therefore, in order to reduce rate of memory disorders measures should be taken to minimize blood loss during operation.%目的 探讨术中失血量对手术患者记忆功能的影响.方法 对282例外科手术患者采用称重法、计量法统计术中出血量,于术前24 h、术后24 h采用行为记忆测验第2版(RBMT-Ⅱ)进行记忆功能的测评.结果 282例患者中,发生术后记忆障碍194例(68.8%),其中轻度98例(50.5%),中度93例(47.9%),重度3例(1.6%);术中失血量>400 mL的患者术后记忆障碍发生率高,且程度重(P<0.01).结论 术中失血量对术后患者的记忆功能有一定的影响,采取积极措施减少术中失血量可降低术后患者记忆障碍的发生率.

  20. Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer's disease mouse models.

    Science.gov (United States)

    Huang, Yunhong; Skwarek-Maruszewska, Aneta; Horré, Katrien; Vandewyer, Elke; Wolfs, Leen; Snellinx, An; Saito, Takashi; Radaelli, Enrico; Corthout, Nikky; Colombelli, Julien; Lo, Adrian C; Van Aerschot, Leen; Callaerts-Vegh, Zsuzsanna; Trabzuni, Daniah; Bossers, Koen; Verhaagen, Joost; Ryten, Mina; Munck, Sebastian; D'Hooge, Rudi; Swaab, Dick F; Hardy, John; Saido, Takaomi C; De Strooper, Bart; Thathiah, Amantha

    2015-10-14

    The orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR3 regulates activity of the γ-secretase complex in the absence of an effect on Notch proteolysis, providing a potential therapeutic target for Alzheimer's disease (AD). However, given the vast resources required to develop and evaluate any new therapy for AD and the multiple failures involved in translational research, demonstration of the pathophysiological relevance of research findings in multiple disease-relevant models is necessary before initiating costly drug development programs. We evaluated the physiological consequences of loss of Gpr3 in four AD transgenic mouse models, including two that contain the humanized murine Aβ sequence and express similar amyloid precursor protein (APP) levels as wild-type mice, thereby reducing potential artificial phenotypes. Our findings reveal that genetic deletion of Gpr3 reduced amyloid pathology in all of the AD mouse models and alleviated cognitive deficits in APP/PS1 mice. Additional three-dimensional visualization and analysis of the amyloid plaque burden provided accurate information on the amyloid load, distribution, and volume in the structurally intact adult mouse brain. Analysis of 10 different regions in healthy human postmortem brain tissue indicated that GPR3 expression was stable during aging. However, two cohorts of human AD postmortem brain tissue samples showed a correlation between elevated GPR3 and AD progression. Collectively, these studies provide evidence that GPR3 mediates the amyloidogenic proteolysis of APP in four AD transgenic mouse models as well as the physiological processing of APP in wild-type mice, suggesting that GPR3 may be a potential therapeutic target for AD drug development.