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Sample records for alzheimers disease neuroimaging

  1. Structural Neuroimaging in Aging and Alzheimer's Disease

    NARCIS (Netherlands)

    Vernooij, Meike W.; Smits, Marion

    2012-01-01

    The role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD) is becoming increasingly important. As a consequence, a basic understanding of what are normal brain changes in aging is key to be able to recognize what is abnormal. The first part of this article discusses normal vers

  2. Neuroimaging Measures as Endophenotypes in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Meredith N. Braskie

    2011-01-01

    Full Text Available Late onset Alzheimer's disease (AD is moderately to highly heritable. Apolipoprotein E allele ε4 (APOE4 has been replicated consistently as an AD risk factor over many studies, and recently confirmed variants in other genes such as CLU, CR1, and PICALM each increase the lifetime risk of AD. However, much of the heritability of AD remains unexplained. AD is a complex disease that is diagnosed largely through neuropsychological testing, though neuroimaging measures may be more sensitive for detecting the incipient disease stages. Difficulties in early diagnosis and variable environmental contributions to the disease can obscure genetic relationships in traditional case-control genetic studies. Neuroimaging measures may be used as endophenotypes for AD, offering a reliable, objective tool to search for possible genetic risk factors. Imaging measures might also clarify the specific mechanisms by which proposed risk factors influence the brain.

  3. Molecular neuroimaging of Alzheimer's disease

    NARCIS (Netherlands)

    Nabuurs, Rob Johannes Antonius

    2014-01-01

    Alzheimer’s disease (AD) is the predominant form of dementia in the aging population and its increasing incidence represents an important socio-economic and public health concern. The hallmarks of this disease, amyloid plaques and neurofibrillary tangles, are thought to develop early in the disease

  4. The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium

    DEFF Research Database (Denmark)

    Frisoni, G.B.; Henneman, W.J.; Weiner, M.W.;

    2008-01-01

    BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven...... academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid...

  5. Neuroimaging in the diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    We sought to identify a marker for Alzheimer's disease (AD) for antemortem diagnosis. To determine whether the detection of reduced blood flow in the parietotemporal cortex, shown by single photon emission CT (SPECT), and of medial temporal lobe atrophy, shown by magnetic resonance imaging (MRI), would be useful in diagnosis, we studied 38 patients with AD diagnosed by the NINCDS-ADRDA criteria and 26 healthy elderly controls. Parietotemporal hypoperfusion was qualitatively assessed by physicians who were unaware of the clinical diagnosis, and the severity of medial temporal lobe atrophy was quantitated by planimetric and linear measurements. Although an accurate diagnosis of AD was made in 80% or more of the patients by SPECT or MRI studies alone, the combination of SPECT and MRI gave a higher diagnostic accuracy, with a sensitivity of 95% and a specificity of 92%. Since regional functional or structural changes were detected in 92% of early or mild patients, including possible AD, the combination of SPECT and MRI studies were useful in the early diagnosis of AD. Findings suggest that a functional abnormality in the parietotemporal lobe and an atrophic change in the medial temporal lobe are characteristic of AD, and that SPECT and MIR regional changes may be useful as antemorten diagnostic markers. (author)

  6. Cross-View Neuroimage Pattern Analysis for Alzheimer's Disease Staging

    Directory of Open Access Journals (Sweden)

    Sidong eLiu

    2016-02-01

    Full Text Available The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD, is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed 9 types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging.

  7. Geriatric medicine, Japanese Alzheimer's disease neuroimaging initiative and biomarker development

    International Nuclear Information System (INIS)

    Due to a change in disease spectrum in aged countries, the primary role of geriatricians should be directed to an appropriate management and prevention of cognitive decline and dementia, swallowing and aspiration pneumonia and falls and fractures. Management of dementia constitutes a central part in the practice of geriatric medicine in order to support independence of life in elderly people. The current paradigm of cognitive function-based testing for the diagnosis and treatment of Alzheimer's disease (AD) is going to drastically shift to a biomarker-based test approach, a shift that will correspond to the emergence of disease-modifying drugs. In addition, a new molecular imaging technique that visualizes neuronal protein deposits or pathological features has been developed in Japan and the U.S.A. Based on these achievements, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was proposed and initiated in 2005. The ADNI is a long-term observational study being conducted in the U.S.A., Europe, Australia, and Japan using identical protocols. The objectives of ADNI are: to establish methodology which will allow standard values related to long-term changes in imaging data, such as MRI and positron emission tomography (PET), in patients with AD and mild cognitive impairment and normal elderly persons; to obtain clinical indices, psychological test data, and blood/cerebrospinal fluid biomarkers to demonstrate the validity of image-based surrogate markers; and to establish optimum methods to monitor the therapeutic effects of disease-modifying drugs for AD. Patient enrollment in the Japanese ADNI has begun in July 2008. Imaging of AD pathology not only acts as a reliable biomarker with which to assay curative drug development by novel pharmaceutical companies, but it also helps health promotion toward AD prevention. (author)

  8. Value of neuropsychological tests, neuroimaging, and biomarkers for diagnosing Alzheimer's disease in younger and older age cohorts

    NARCIS (Netherlands)

    B. Schmand; P. Eikelenboom; W.A. van Gool

    2011-01-01

    OBJECTIVES: To examine the influence of age on the value of four techniques for diagnosing Alzheimer's disease (AD). DESIGN: Observational cohort study. SETTING: Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: Individuals with mild cognitive impairment (MCI; n=179), individuals with AD (n

  9. Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI)

    DEFF Research Database (Denmark)

    Buerger, Katharina; Frisoni, Giovanni; Uspenskaya, Olga;

    2009-01-01

    BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHODS...

  10. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    Science.gov (United States)

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  11. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls.

    Science.gov (United States)

    Barnes, Josephine; Carmichael, Owen T; Leung, Kelvin K; Schwarz, Christopher; Ridgway, Gerard R; Bartlett, Jonathan W; Malone, Ian B; Schott, Jonathan M; Rossor, Martin N; Biessels, Geert Jan; DeCarli, Charlie; Fox, Nick C

    2013-08-01

    This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p brain atrophy in the context of AD pathology in pre-dementia stages.

  12. The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tie-Qiang (Karolinska Huddinge - Medical Physics, Stockholm (Sweden)), email: tieqiang.li@karolinska.se; Wahlund, Lars-Olof (Dept. of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm (Sweden))

    2011-02-15

    The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS)

  13. Multimodal MRI Neuroimaging Biomarkers for Cognitive Normal Adults, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Ai-Ling Lin

    2012-01-01

    Full Text Available Multimodal magnetic resonance imaging (MRI techniques have been developed to noninvasively measure structural, metabolic, hemodynamic and functional changes of the brain. These advantages have made MRI an important tool to investigate neurodegenerative disorders, including diagnosis, disease progression monitoring, and treatment efficacy evaluation. This paper discusses recent findings of the multimodal MRI in the context of surrogate biomarkers for identifying the risk for AD in normal cognitive (NC adults, brain anatomical and functional alterations in amnestic mild cognitive impairment (aMCI, and Alzheimer's disease (AD patients. Further developments of these techniques and the establishment of promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and AD in their early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

  14. Multivariate protein signatures of pre-clinical Alzheimer's disease in the Alzheimer's disease neuroimaging initiative (ADNI plasma proteome dataset.

    Directory of Open Access Journals (Sweden)

    Daniel Johnstone

    Full Text Available BACKGROUND: Recent Alzheimer's disease (AD research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI, allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. METHODS AND FINDINGS: We focused on identifying signatures that discriminate cognitively normal controls (n = 54 from individuals with MCI who subsequently progress to AD (n = 163. Based on p value, apolipoprotein E (APOE showed the strongest difference between these groups (p = 2.3 × 10(-13. We applied a multivariate approach based on combinatorial optimization ((α,β-k Feature Set Selection, which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering "meta-features," representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. CONCLUSIONS: Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of

  15. Intrinsic functional component analysis via sparse representation on Alzheimer's disease neuroimaging initiative database.

    Science.gov (United States)

    Jiang, Xi; Zhang, Xin; Zhu, Dajiang

    2014-10-01

    Alzheimer's disease (AD) is the most common type of dementia (accounting for 60% to 80%) and is the fifth leading cause of death for those people who are 65 or older. By 2050, one new case of AD in United States is expected to develop every 33 sec. Unfortunately, there is no available effective treatment that can stop or slow the death of neurons that causes AD symptoms. On the other hand, it is widely believed that AD starts before development of the associated symptoms, so its prestages, including mild cognitive impairment (MCI) or even significant memory concern (SMC), have received increasing attention, not only because of their potential as a precursor of AD, but also as a possible predictor of conversion to other neurodegenerative diseases. Although these prestages have been defined clinically, accurate/efficient diagnosis is still challenging. Moreover, brain functional abnormalities behind those alterations and conversions are still unclear. In this article, by developing novel sparse representations of whole-brain resting-state functional magnetic resonance imaging signals and by using the most updated Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we successfully identified multiple functional components simultaneously, and which potentially represent those intrinsic functional networks involved in the resting-state activities. Interestingly, these identified functional components contain all the resting-state networks obtained from traditional independent-component analysis. Moreover, by using the features derived from those functional components, it yields high classification accuracy for both AD (94%) and MCI (92%) versus normal controls. Even for SMC we can still have 92% accuracy.

  16. 2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Luthman, Johan; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W; Trojanowski, John Q

    2015-06-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers,

  17. Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Hasselbalch, Steen G; Gade, Anders;

    2005-01-01

    To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD)....

  18. Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Hasselbalch, Steen G; Gade, Anders;

    2005-01-01

    To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD).......To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with 'amnestic mild cognitive impairment' (MCI) and mild Alzheimer's disease (AD)....

  19. Effect of HMGCR genetic variation on neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts

    Science.gov (United States)

    Tan, Lin; Sun, Fu-Rong; Tan, Meng-Shan; Tan, Chen-Chen; Jiang, Teng; Yu, Jin-Tai; Tan, Lan

    2016-01-01

    Alzheimer's disease (AD) has become a considerable public health issue. The mechanisms underlying AD onset and progression remain largely unclear. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a strong functional AD candidate gene because it encodes part of the statin-binding domain of the enzyme, which serves as the rate-limiting step in cholesterol synthesis in all mammalian cells. Here, we evaluated the potential role of HMGCR (rs3846662) in AD-related pathology by assessing neuroimaging biomarkers. We enrolled in 812 subjects from the Alzheimer's disease Neuroimaging Initiative dataset. In general, it is possible that HMGCR (rs3846662) could be involved in preventing the atrophy of right entorhinal (P=0.03385) and left hippocampus (P=0.01839) in the follow-up research of two years. What's more, it lowered the drop rate of glucose metabolism in right temporal. We then further validated them in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. All the results in the MCI groups confirmed the association. The results of our study indicated that HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression. PMID:26950278

  20. The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What role do public-private partnerships have in pushing the boundaries of clinical and basic science research on Alzheimer's disease?

    Science.gov (United States)

    Jones-Davis, Dorothy M; Buckholtz, Neil

    2015-07-01

    In the growing landscape of biomedical public-private-partnerships, particularly for Alzheimer's disease, the question is posed as to their value. What impacts do public-private-partnerships have on clinical and basic science research in Alzheimer's disease? The authors answer the question using the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an exemplar of how public-private-partnerships can make an impact not only on clinical and basic science research and practice (including clinical trials), but also of how similar partnerships using ADNI as an example, can be designed to create a maximal impact within their fields. PMID:26194319

  1. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative.

    Science.gov (United States)

    Madsen, Sarah K; Rajagopalan, Priya; Joshi, Shantanu H; Toga, Arthur W; Thompson, Paul M

    2015-01-01

    A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital, and right temporal regions and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, patients with mild cognitive impairment, or patients with Alzheimer's disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels. PMID:25444607

  2. The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

    Directory of Open Access Journals (Sweden)

    Luiz K. Ferreira

    2014-12-01

    Full Text Available Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs, Alzheimer's disease (AD, and mild cognitive impairment (MCI. Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET, single photon emission computerized tomography (SPECT, or functional magnetic resonance imaging (fMRI. Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures. In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD.

  3. Clinical differentiation between frontotemporal dementia and Alzheimers disease : Psychometric, behavioral, neuroimaging and neurophysiological information

    OpenAIRE

    Lindau, Maria

    2002-01-01

    Frontotemporal dementia (FTD) initially affects the anterior regions of the brain, and gradually spreads to other cerebral areas. Behavioral alterations are described as the hallmark of FTD, whereas cognition is mostly found to be relatively spared. Alzheimer's disease (AD) starts in the posterior brain areas, and successively involves even other regions. Typical for AD are cognitive deficits, but behavioral and emotional changes have also been reported. With progression, th...

  4. DIAGNOSIS-GUIDED METHOD FOR IDENTIFYING MULTI-MODALITY NEUROIMAGING BIOMARKERS ASSOCIATED WITH GENETIC RISK FACTORS IN ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Zhang, Daoqiang; Shen, Li

    2016-01-01

    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods.

  5. Association between NME8 locus polymorphism and cognitive decline, cerebrospinal fluid and neuroimaging biomarkers in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ying Liu

    Full Text Available Recently, a large meta-analysis of five genome wide association studies (GWAS identified a novel locus (rs2718058 adjacent to NME8 that played a preventive role in Alzheimer's disease (AD. However, this link between the single nucleotide polymorphism (SNP rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI database. We used information of a total of 719 individuals, including 211 normal cognition (NC, 346 mild cognitive impairment (MCI and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P = 0.021. Occipital gyrus atrophy were significantly associated with NME8 genotype status (P = 0.002, with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left cerebral metabolic rate for glucose (CMRgl were significantly associated with NME8 genotype (P < 0.05, with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration.

  6. Alzheimer disease

    Science.gov (United States)

    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more likely ...

  7. Neuroimaging of hippocampal atrophy in early recognition of Alzheimer's disease--a critical appraisal after two decades of research.

    Science.gov (United States)

    Schröder, Johannes; Pantel, Johannes

    2016-01-30

    As a characteristic feature of Alzheimer's disease (AD) hippocampal atrophy (HA) can be demonstrated in the majority of patients by using neuroimaging techniques in particular magnetic resonance imaging (MRI). Hippocampal atrophy is associated with declarative memory deficits and can also be associated with changes of adjacent medial temporal substructures such as the parahippocampal gyrus or the the entorhinal cortex. Similar findings are present in patients with mild cognitive impairment (MCI) albeit to a lesser extent. While these finding facilitate the diagnostic process in patients with clinical suspicious AD, the metric properties of hippocampal atrophy for delineating healthy aging from MCI and mild AD still appear to be rather limited; as such it is not sufficient to establish the diagnosis of AD (and even more so of MCI). This limitation partly refers to methodological issues and partly to the fact that hippocampal tissue integrity is subject to various pathogenetic influences other than AD. Moreover,the effects of hippocampal atrophy on the behavioral level (e.g. cognitive deficits) are modulated by the individual's cognitive reserve. From a clinical standpoint these observations are in line with the hypothesis that the onset and course of AD is influenced by a number of peristatic factors which are partly conceptualized in the concepts of brain and/or cognitive reserve. These complex interactions have to be considered when using the presence of hippocampal atrophy in the routine diagnostic procedure of AD.

  8. Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence.

    Science.gov (United States)

    Bai, Feng; Shi, Yongmei; Yuan, Yonggui; Xie, Chunming; Zhang, Zhijun

    2016-08-01

    Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD. PMID:26899953

  9. Alzheimer's Disease

    Science.gov (United States)

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  10. Alzheimer's disease.

    Science.gov (United States)

    De-Paula, Vanessa J; Radanovic, Marcia; Diniz, Breno S; Forlenza, Orestes V

    2012-01-01

    , and highest estimates in old age. According to recent propositions, three clinical phases of Alzheimer's disease may be defined: (i) pre-symptomatic (or pre-clinical) AD, which may last for several years or decades until the overproduction and accumulation of Aβ in the brain reaches a critical level that triggers the amyloid cascade; (ii) pre-dementia phase of AD (compatible with the definition of progressive, amnestic mild cognitive impairment), in which early-stage pathology is present, ranging from mild neuronal dystrophy to early-stage Braak pathology, and may last for several years according to individual resilience and brain reserve; (iii) clinically defined dementia phase of AD, in which cognitive and functional impairment is severe enough to surmount the dementia threshold; at this stage there is significant accumulation of neuritic plaques and neurofibrillary tangles in affected brain areas, bearing relationship with the magnitude of global impairment. New technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid may depict correlates of intracerebral amyloidosis in individuals with mild, pre-dementia symptoms. These methods are commonly referred to as AD-related biomarkers, and the combination of clinical and biological information yields good diagnostic accuracy to identify individuals at high risk of AD. In other words, the characterization of pathogenic Aβ by means of biochemical analysis of biological fluids or by molecular neuroimaging are presented as diagnostic tools to help identify AD cases at the earliest stages of the disease process. The relevance of this early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are more likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Therapies targeting the modification of amyloid-related cascades may be viewed as promising strategies to

  11. Predicting Alzheimer's disease development: a comparison of cognitive criteria and associated neuroimaging biomarkers

    OpenAIRE

    Callahan, Brandy L.; Ramirez, Joel; Berezuk, Courtney; Duchesne, Simon; Black, Sandra E.; ,

    2015-01-01

    Introduction The definition of “objective cognitive impairment” in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer’s disease (AD) from baseline to 24 months. Methods The sensitivity and specificity of six methods of defining episodic memory impairment (< −1, −1.5 or −2 standard deviations [SD] on ...

  12. Neuroimaging diagnosis in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Dementia affects about 8% of people age 65 years and older. Identification of dementia is particularly difficult in its early phases when family members and physicians often incorrectly attribute the patients symptoms to normal aging. The most frequently occurring ailments that are connected with neuro degeneration are: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. A variety of powerful techniques that have allowed visualization of organ structure and function with exact detail have been introduced in the last twenty-five years. One such neuroimaging technique is positron emission tomography (PET), which measures in detail the functioning of distinct areas of the human brain and as a result plays a critical role in clinical and research applications. Radiotracer-based functional imaging provides a sensitive means of recognizing and characterizing the regional changes in brain metabolism and receptor binding associated with cognitive disorders. The next functional imaging technique widely used in the diagnosis of cognitive disorders is single photon emission computed tomography (SPECT). New radiotracers are being developed and promise to expand further the list of indications for PET. Prospects for developing new tracers for imaging other organ diseases also appear to be very promising. In this review, we present current opportunities of neuroimaging techniques in the diagnosis and differentiation of neuro degenerative disorders. (authors)

  13. Alzheimer's disease

    OpenAIRE

    Schachter, Armand S.; Davis, Kenneth L.

    2000-01-01

    Alzheimer's disease is one of the most devastating brain disorders of elderly humans. It is an undertreated and under-recognized disease that is becoming a major public health problem. The last decade has witnessed a steadily increasing effort directed at discovering the etiology of the disease and developing pharmacological treatment. Recent developments include improved clinical diagnostic guidelines and improved treatment of both cognitive disturbance and behavioral problems. Symptomatic t...

  14. Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.

    Science.gov (United States)

    Ramanan, Vijay K; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L; Foroud, Tatiana M; Mukherjee, Shubhabrata; Crane, Paul K; Aisen, Paul S; Petersen, Ronald C; Weiner, Michael W; Saykin, Andrew J

    2012-12-01

    Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions. PMID:22865056

  15. Alzheimer's Disease Information Page

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Alzheimer's Disease Information Page Table of Contents (click to ... en Español Additional resources from MedlinePlus What is Alzheimer's Disease? Alzheimer's disease (AD) is an age-related, ...

  16. Advances on Alzheimer's Disease With Neuroimaging%阿尔茨海默病的神经影像学研究进展

    Institute of Scientific and Technical Information of China (English)

    贺永

    2012-01-01

    Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by impaired memory and other cognitive functions. Previous neuroimaging studies have demonstrated regional structural and functional changes. Recent progressions on multi-modal imaging techniques and human brain connectome methods have allowed us to explore alterations of structural and functional networks in AD. Using these approaches, many studies have discovered AD-related network disruption, including connectivity strength, network efficiency, modular structure and network hubs. These findings provide novel insights into the understanding of AD notion of network disintegration and might lead to uncover disease biomarker for early diagnosis in AD. Most importantly, these findings in AD have been also demonstrated in the individuals at risk for AD (e.g., mild cognitive impairment), suggesting that the neuroimaging studies of AD should be moved into the prodromal stage of AD from the dementia stage.%阿尔茨海默病(Alzheimer's disease,AD)是以记忆和其他高级认知功能下降为特征的神经退行性疾病.早期的神经影像学研究通常是探索AD患者局部脑区的结构和功能变化.随着多模态神经影像技术和人脑连接组学研究方法的发展,研究者已经能够考察AD患者脑结构和功能连接通路.采用这些方法,最近的研究已经发现,AD患者脑网络的连接强度、网络效率、模块化组织和核心脑区连接的下降,并发现这些变化与患者的记忆评分等密切相关.这些新方法和新技术的出现不仅提供了新颖的观点来解释AD病的脑区失连接病理生理机制,而且发现的AD异常脑连接模式可能作为敏感特征应用于AD早期辅助诊断的影像标记物研究.特别重要的是,研究表明,在AD患者脑神经网络出现的异常连接模式,在AD前期即轻度认知障碍期患者中也已出现,表明了将AD影像学研究的重点前移到AD前期这一可治

  17. Treatments for Alzheimer's Disease

    Science.gov (United States)

    ... Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? Younger/Early Onset Facts and Figures Know the 10 Signs Stages Inside the Brain: ...

  18. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions Alzheimer disease Alzheimer disease Enable Javascript to view the expand/collapse boxes. Print All Open All Close All Description Alzheimer disease is a degenerative disease of the brain ...

  19. Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study

    OpenAIRE

    Mosconi, Lisa; Murray, John; Davies, Michelle; Williams, Schantel; Pirraglia, Elizabeth; Spector, Nicole; Tsui, Wai H; Li, Yi; Butler, Tracy; Osorio, Ricardo S.; Glodzik, Lidia; Vallabhajosula, Shankar; mcHugh, Pauline; Marmar, Charles R.; de Leon, Mony J.

    2014-01-01

    Objective There is increasing evidence to suggest that diet, one of the most important modifiable environmental factors, may play a role in preventing or delaying cognitive decline and Alzheimer's disease (AD). This study examines the relationship between dietary nutrients and brain biomarkers of AD in cognitively normal individuals (NL) with and without AD risk factors. Design As part of an ongoing brain imaging study, participants received clinical and laboratory examinations, a neurocognit...

  20. Alzheimer's Disease Facts and Figures

    Science.gov (United States)

    ... Alzheimer's >> Home Text size: A A A 2016 Alzheimer's Disease Facts and Figures download the full report: ... or even slowed. Invest in a world without Alzheimer's. Donate Caregivers In 2015, 15.9 million family ...

  1. Neuroinflammation in Alzheimer's disease

    NARCIS (Netherlands)

    Heneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederic; Feinstein, Douglas L.; Jacobs, Andreas H.; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M.; Herrup, Karl; Frautschy, Sally A.; Finsen, Bente; Brown, Guy C.; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C.; Town, Terrence; Morgan, Dave; Shinohara, Mari L.; Perry, V. Hugh; Holmes, Clive; Bazan, Nicolas G.; Brooks, David J.; Hunot, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.

    2015-01-01

    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigg

  2. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

    Heneka, Michael T; Carson, Monica J; Khoury, Joseph El;

    2015-01-01

    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and tr...

  3. New criteria for diagnosing Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Andrei Yuryevich Emelin

    2011-01-01

    Full Text Available Department of Nervous Diseases, S.M. Kirov Military Medical Academy, Saint Petersburg The paper gives an analysis of new diagnostic criteria for different stages of Alzheimer Х s disease (AD, which is proposed by the U.S. National Institute on Aging. It considers possibilities for the early diagnosis of AD, including its preclinical diagnosis using the laboratory and neuroimaging markers beta-amyloid, neuronal damage.

  4. [Alzheimer and the discovery of Alzheimer's disease].

    Science.gov (United States)

    Zhagn, Lili; Li, Zhiping

    2014-09-01

    Alzheimer was born in Germany in 1864. In 1887, Alzheimer graduated with a medical doctor degree at the University of Würzburg. In 1888, Alzheimer began to work in the Community Hospital for Mental and Epileptic Patients in Frankfurt am Main for 14 years. During this time, Alzheimer published the six-volume Histologic and Histopathologic Studies of the Cerebral Cortex, with co-author Franz Nissl. In 1903, Alzheimer came to work in the Royal Psychiatric Clinic of the University of Munich. One year later, he published his postdoctoral paper of Histological Studies about the Differential Diagnosis of Progressive Paralysis in 1904. In 1912, Alzheimer was provided the chair of psychiatry at the University of Breslau. On the way to Breslau, Alzheimer got sick, and eventually died in 1915. In 1906, Alzheimer found numerous amyloid plaques and neurofibrillary tangles in the brain of a patient called Auguste under the microscope. In November of the same year, Alzheimer gave a lecture about Auguste's case at the 37(th) Conference of South-West German Psychiatrists in Tübingen, which received little attention. In 1910, Kraepelin mentioned "Alzheimer's disease" for the first time to name the disease of what Auguste got in the 8th edition of Handbook of Psychiatry. Therefore, Alzheimer achieved worldwide recognition.

  5. A disease state fingerprint for evaluation of Alzheimer's disease

    DEFF Research Database (Denmark)

    Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho;

    2011-01-01

    Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease...

  6. Fusing Heterogeneous Data for Alzheimer's Disease Classification.

    Science.gov (United States)

    Pillai, Parvathy Sudhir; Leong, Tze-Yun

    2015-01-01

    In multi-view learning, multimodal representations of a real world object or situation are integrated to learn its overall picture. Feature sets from distinct data sources carry different, yet complementary, information which, if analysed together, usually yield better insights and more accurate results. Neuro-degenerative disorders such as dementia are characterized by changes in multiple biomarkers. This work combines the features from neuroimaging and cerebrospinal fluid studies to distinguish Alzheimer's disease patients from healthy subjects. We apply statistical data fusion techniques on 101 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We examine whether fusion of biomarkers helps to improve diagnostic accuracy and how the methods compare against each other for this problem. Our results indicate that multimodal data fusion improves classification accuracy. PMID:26262148

  7. Cerebrolysin in Alzheimer's disease.

    Science.gov (United States)

    Antón Álvarez, X; Fuentes, Patricio

    2011-07-01

    Cerebrolysin is a neuropeptide preparation mimicking the action of endogenous neurotrophic factors. Positive effects of Cerebrolysin on β-amyloid- and tau-related pathologies, neuroinflammation, neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuroplasticity, neuronal apoptosis and degeneration, neurogenesis and cognition were demonstrated in experimental conditions. These pleiotropic effects of Cerebrolysin on Alzheimer's disease-related pathogenic events are consistent with a neurotrophic-like mode of action, and seems to involve the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 β intracellular signaling pathway. The clinical efficacy of Cerebrolysin in Alzheimer's disease was evaluated in several randomized, double-blind, clinical trials, showing consistent benefits on global clinical function and cognition, improvements in behavior at high doses, and minor effects on daily living activities in patients with mild to moderate Alzheimer's disease, as well as in subgroups of moderate to moderately severe patients. In addition, the clinical benefits of Cerebrolysin were largely maintained for several months after ending treatment, a finding that supports its discontinuous administration. Cerebrolysin was generally well tolerated and did not induce significant adverse events in Alzheimer's patients. Although long-term studies are needed, the data available suggest that Cerebrolysin is effective as monotherapy and constitutes a promising option for combined therapy in Alzheimer's disease.

  8. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    ... TDP43-related Dementia 2013 Andrew Watt Characterisation of Tau Imaging Ligands for Alzheimer's Disease and other Dementias 2010 Marco Prado The Prion Protein as a Therapeutic Target in Alzheimer's Disease 2007 ...

  9. Early diagnosis of Alzheimer's disease. Clinical significance and future perspectives

    International Nuclear Information System (INIS)

    Early diagnosis of Alzheimer's disease describes the recognition and diagnosis in patients with very mild dementia. Internationally accepted diagnostic criteria support the diagnosis based on clinical evaluation. Recent advances in structural and functional neuroimaging as well as studies on specific proteins in the cerebro-spinal fluid that are related to distinct pathophysiological disease processes are most promising approaches to defining biological markers of Alzheimer's disease. (orig.)

  10. Biomarkers for early detection of Alzheimer disease.

    Science.gov (United States)

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  11. Data acquisition, curation and modeling for integration of Alzheimer's disease neuroimaging data from ADNI in the translational biomedicine platform tranSMART

    OpenAIRE

    Veríssimo, Vasco de Almeida Jorge

    2015-01-01

    Tese de mestrado integrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015 Nos dias que correm, as doenças neurodegenerativas afetam milhões de pessoas em todo o mundo, havendo mais de 600 doenças diferentes que incidem sobre o sistema nervoso, sendo as doenças de Alzheimer e Parkinson as mais comuns. Estudos indicam que 60-70% das pessoas que sofrem de distúrbios cerebrais, são casos de Alzheimer. Se olharmos para os Estado...

  12. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease

    OpenAIRE

    Bateman, R.J.; Aisen, P.S.; De Strooper, B.; Fox, N C; Lemere, C. A.; Ringman, J.M.; Salloway, S; Sperling, R. A.; Windisch, M.; Xiong, C.

    2011-01-01

    Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are...

  13. Caregiving for Alzheimer's Disease or Other Dementia

    Science.gov (United States)

    ... What's this? Submit Button Caregiving for Person with Alzheimer's Disease or a related Dementia Recommend on Facebook Tweet Share Compartir What is Alzheimer's Disease? Alzheimer's disease is the most common form of ...

  14. Exosomes in Alzheimer's disease.

    Science.gov (United States)

    Malm, Tarja; Loppi, Sanna; Kanninen, Katja M

    2016-07-01

    Exosomes, nano-sized extracellular vesicles secreted by most cell types, are found everywhere in the body. The role of exosomes in cellular functions has in the past years developed from being considered little more than cellular trashcans, to being proven important intercellular messengers and notable contributors to both health and in disease. A vast number of studies have revealed the multiple, and somewhat controversial role of exosomes in Alzheimer's disease, the most common neurodegenerative disease. Exosomes have been shown to spread toxic amyloid-beta and hyperphosphorylated tau between cells, and they have been suspected of inducing apoptosis and thereby contributing to neuronal loss. On the other hand, exosomes seem to possess the ability to reduce brain amyloid-beta through microglial uptake, and they are known to transfer neuroprotective substances between cells. These features, among many others, make exosomes extremely interesting from the point of view of developing novel therapeutic approaches. The fact that exosomes derived from the central nervous system can be found in bodily fluids also makes them an appealing target for biomarker development, which is not limited only to Alzheimer's disease. PMID:27131734

  15. A disease state fingerprint for evaluation of Alzheimer's disease

    DEFF Research Database (Denmark)

    Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho;

    2011-01-01

    Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization...... system is proposed for supporting clinical diagnosis of AD. The proposed system computes an evidence-based estimate of a patient's AD state by comparing his or her heterogeneous neuropsychological, clinical, and biomarker data to previously diagnosed cases. The AD state in this context denotes a patient...... interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease...

  16. Identical twins with Alzheimer's disease.

    OpenAIRE

    Kilpatrick, C; Burns, R; Blumbergs, P C

    1983-01-01

    Genetically proven identical twin sisters with Alzheimer's disease are reported. Both sisters at the age of fifty years developed a dementing illness. Their mother and maternal grandmother developed at the same age a similar illness. It is suggested that in some cases of familial Alzheimer's disease the condition is inherited by a single mutant gene.

  17. Alzheimer's Disease Beyond Abeta.

    Science.gov (United States)

    Town, Terrence

    2010-05-01

    Many of the Alzheimer's disease (AD) clinical trials have made it far enough down the pipeline to allow conclusions about targeting the amyloid-beta peptide (Abeta) as a therapeutic approach. Based on these results, it is becoming clear that a multifocal approach to AD treatment is probably necessary. However, critical discussion beyond Abeta is necessary to enable the next wave of AD therapeutic targets. For this reason, the 2010 Keystone Symposium, 'Alzheimer's Disease Beyond Abeta', was organized by JoAnne McLaurin and Tony Wyss-Coray to spark topical discussion and debate. While researchers struggled to get beyond that ever-present pathognomonic feature of AD, new and exciting evidence was presented that raised our awareness of what is around the corner for next-generation AD therapeutics beyond Abeta. This report will describe some of the highlights from Copper Mountain Resort throughout the meeting period of 10-15 January 2010 in Colorado (USA). Despite illuminating scientific presentations and intense discussions, a number of important questions remain concerning the best biomarkers and targets to focus on, and when and how to therapeutically intervene. PMID:20429127

  18. Micronutrients and Alzheimer's disease.

    Science.gov (United States)

    Staehelin, Hannes B

    2005-11-01

    The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-beta42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B(12) and B(6)). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long. PMID:16313699

  19. Immunotherapy for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Weihua Wang; Liangfeng Fan; De'en Xu; Zhongmin Wen; Rong Yu; Quanhong Ma

    2012-01-01

    Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) plaques consisted primarily of aggregated Aβ proteins and neurofibrillary tangles formed by hyperphosphorylated tau protein.Both Aβ and hyperphosphorylated tau are toxic both in vivo and in vitro.Immunotherapy targeting Aβ seems to provide a promising approach to reduce the toxic species in the brain.However,there is little evidence from clinical trials so far indicating the efficacy of Aβ immunotherapy in cognitive improvement.Immunization with tau peptides or anti-tau antibodies could remove the tau aggregates and improve the cognitive function in preclinical study,which provides a novel strategy of AD therapy.In this article,we will summarize the immunotherapeutic strategies targeting either Aβ or tau.

  20. Treatment for Alzheimer's diseases

    Directory of Open Access Journals (Sweden)

    Nina Arkadyevna Tyuvina

    2015-01-01

    Full Text Available The paper gives an update on the epidemiology, etiology, pathogenesis, prevention, and treatment of Alzheimer's disease (AD. It points out the role of acetylcholine and glutamatergic components of neurotransmission in the pathogenesis of the disease, as well as their interactions, which is important to keep in mind to have a potentiated response to therapy that includes both these components. Different approaches to AD therapy are considered on the basis of the current ideas on the pathogenetic mechanisms of a degenerative process and with regard to the clinical features of the disease (the nature of the psychopathological symptoms of the disease and its stage. Particular emphasis is placed on compensatory therapy for deficient cholinergic and glutamatergic neurotransmission. Whether psychopharmacological agents may be used and psychotherapeutic work with the relatives of patients with AD should be done are also highlighted. Data on the efficiency of replacement therapy for different dementia stages, which promotes a delay in degenerative processes and a definite stabilization of the mental status, are presented.

  1. Microwaves and Alzheimer's disease

    Science.gov (United States)

    Zhang, Xia; Huang, Wen-Juan; Chen, Wei-Wei

    2016-01-01

    Alzheimer's diseases (AD) is the most common type of dementia and a neurodegenerative disease that occurs when the nerve cells in the brain die. The cause and treatment of AD remain unknown. However, AD is a disease that affects the brain, an organ that controls behavior. Accordingly, anything that can interact with the brain may affect this organ positively or negatively, thereby protecting or encouraging AD. In this regard, modern life encompasses microwaves for all issues including industrial, communications, medical and domestic tenders, and among all applications, the cell phone wave, which directly exposes the brain, continues to be the most used. Evidence suggests that microwaves may produce various biological effects on the central nervous system (CNS) and many arguments relay the possibility that microwaves may be involved in the pathophysiology of CNS disease, including AD. By contrast, previous studies have reported some beneficial cognitive effects and that microwaves may protect against cognitive impairment in AD. However, although many of the beneficial effects of microwaves are derived from animal models, but can easily be extrapolated to humans, whether microwaves cause AD is an important issue that is to be addressed in the current review.

  2. Useful Information on...Alzheimer's Disease.

    Science.gov (United States)

    Cohen, Gene D.

    This brochure provides information on Alzheimer's disease by examining who gets Alzheimer's disease and what to expect when someone has Alzheimer's disease. Abnormal brain tissue findings are discussed and three clinical features of Alzheimer's disease are listed: dementia; insidious onset of symptoms; and exclusion of all other specific causes of…

  3. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease

  4. Alzheimer's disease--one clinical syndrome, two radiological expressions: a study on blood pressure.

    NARCIS (Netherlands)

    Leeuw, H.F. de; Barkhof, F.; Scheltens, P.

    2004-01-01

    BACKGROUND: Vascular risk factors could play a role in the aetiology of Alzheimer's disease, but this has not been investigated in relation to neuroimaging findings OBJECTIVE: To evaluate the distribution of blood pressure and an indicator of atherosclerosis (pulse pressure) in patients with Alzheim

  5. CSF Biomarkers for Alzheimer's Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    A. Anoop

    2010-01-01

    Full Text Available Alzheimer's disease (AD is the most common form of dementia that affects several million people worldwide. The major neuropathological hallmarks of AD are the presence of extracellular amyloid plaques that are composed of Aβ40 and Aβ42 and intracellular neurofibrillary tangles (NFT, which is composed of hyperphosphorylated protein Tau. While the amyloid plaques and NFT could define the disease progression involving neuronal loss and dysfunction, significant cognitive decline occurs before their appearance. Although significant advances in neuroimaging techniques provide the structure and physiology of brain of AD cases, the biomarker studies based on cerebrospinal fluid (CSF and plasma represent the most direct and convenient means to study the disease progression. Biomarkers are useful in detecting the preclinical as well as symptomatic stages of AD. In this paper, we discuss the recent advancements of various biomarkers with particular emphasis on CSF biomarkers for monitoring the early development of AD before significant cognitive dysfunction.

  6. [Vitamin E and Alzheimer's Disease].

    Science.gov (United States)

    Shinohara, Moeko; Yamada, Masahito

    2015-12-01

    It has been suggested that oxidative stress may contribute to the pathogenesis of Alzheimer's disease. Vitamin E is a potent antioxidant, and the results of some epidemiological studies have suggested that high intake of vitamin E through food is inversely associated with the incidence of Alzheimer's disease. Randomized controlled studies have shown that treatment with vitamin E could delay functional decline in patients with mild to moderate Alzheimer's disease. However, vitamin E had no cognitive benefits in patients with mild cognitive impairment or in generally healthy older women. Well-designed clinical trials or preventive interventions with vitamin E are necessary to establish its efficacy as therapeutic or preventive agents for Alzheimer's disease. PMID:26618765

  7. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  8. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

  9. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

    This book contains 21 selections. Some of the titles are: Dementia of the Alzheimer Type: Genetic Aspects; Determination of Cerebral Metabolic Patterns in Dementia Using Positron Emission Tomography; Pathology of the Basal Forebrain in Alzheimer's Disease and Other Dementias; Characterization of Neurofibrillary Tangles with Monoclonal Antibodies Raised Against Alzheimer Neurofibrillary Tangles; and HLA Associations in Alzheimer's Disease

  10. [Music therapy and Alzheimer disease].

    Science.gov (United States)

    Tromeur, Emilie

    2014-01-01

    Music therapy and Alzheimer's dementia. Dementia such as Alzheimer's leads to the deterioration of the patient's global capacities. The cognitive disorders associated with it are disabling and affect every area of the patient's life. Every therapy's session undertaken with and by patients can act as a mirror of the progress of their disease and help to feel better, as described in this article on music therapy. PMID:24908841

  11. Mitochondrial haplotypes associated with biomarkers for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    Full Text Available Various studies have suggested that the mitochondrial genome plays a role in late-onset Alzheimer's disease, although results are mixed. We used an endophenotype-based approach to further characterize mitochondrial genetic variation and its relationship to risk markers for Alzheimer's disease. We analyzed longitudinal data from non-demented, mild cognitive impairment, and late-onset Alzheimer's disease participants in the Alzheimer's Disease Neuroimaging Initiative with genetic, brain imaging, and behavioral data. We assessed the relationship of structural MRI and cognitive biomarkers with mitochondrial genome variation using TreeScanning, a haplotype-based approach that concentrates statistical power by analyzing evolutionarily meaningful groups (or clades of haplotypes together for association with a phenotype. Four clades were associated with three different endophenotypes: whole brain volume, percent change in temporal pole thickness, and left hippocampal atrophy over two years. This is the first study of its kind to identify mitochondrial variation associated with brain imaging endophenotypes of Alzheimer's disease. Our results provide additional evidence that the mitochondrial genome plays a role in risk for Alzheimer's disease.

  12. Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Holm, I.E.; Schwartz, M.;

    2008-01-01

    We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic an......We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre...

  13. Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Living with Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... delay or prevent the disease. Free Guide for Alzheimer's Caregivers Caring for a person with Alzheimer's disease ...

  14. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Kessels, R.P.C.

    2013-01-01

    Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function.

  15. Early detection of Alzheimer's disease using MRI hippocampal texture

    DEFF Research Database (Denmark)

    Sørensen, Lauge; Igel, Christian; Hansen, Naja Liv;

    2016-01-01

    Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change in hippocam......Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change...... in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently...

  16. Functional Neuroimaging of Motor Control inParkinson’s Disease

    DEFF Research Database (Denmark)

    Herz, Damian M; Eickhoff, Simon B; Løkkegaard, Annemette;

    2014-01-01

    Functional neuroimaging has been widely used to study the activation patterns of the motor network in patients with Parkinson's disease (PD), but these studies have yielded conflicting results. This meta-analysis of previous neuroimaging studies was performed to identify patterns of abnormal...

  17. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  18. Coping & Caring: Living with Alzheimer's Disease.

    Science.gov (United States)

    Leroux, Charles

    This guide on Alzheimer's disease is for those who care for Alzheimer's patients, as well as those who want to learn more about the disease. It answers these questions: (1) what is Alzheimer's? (2) how does the disease progress and how long does it last? (3) how do families cope? and (4) who can provide assistance and information? The guide also…

  19. Cerebral imaging revealing Alzheimer's disease

    International Nuclear Information System (INIS)

    Cerebral imaging is the only non-invasive means of examining the brain and is essential in studying Alzheimer's disease. As a tool for early diagnosis, evaluation and treatment monitoring, this technology is at the heart of the research being done to further improve its reliability and sensitivity. (authors)

  20. Alzheimer's disease and euthanasia.

    Science.gov (United States)

    Alvargonzález, David

    2012-12-01

    Employing the tenets of philosophical materialism, this paper discusses the ethical debate surrounding assisted suicide for persons suffering end-stage Alzheimer's. It first presents a classification of the dissociative situations between "human individual" and "human person". It then moves on to discuss challenges to diagnosed persons and their caregivers in relation to the cardinal virtues of Spinozistic ethics--strength of character (fortitudo), firmness (animositas) and generosity (generositas). Finally, a number of ideas attached to the debate--"right of choice", "death with dignity", "quality of life" and "compassion in dying"--are discussed in order to clarify their foundations. PMID:22939533

  1. Assessing neuronal networks: understanding Alzheimer's disease.

    LENUS (Irish Health Repository)

    Bokde, Arun L W

    2012-02-01

    Findings derived from neuroimaging of the structural and functional organization of the human brain have led to the widely supported hypothesis that neuronal networks of temporally coordinated brain activity across different regional brain structures underpin cognitive function. Failure of integration within a network leads to cognitive dysfunction. The current discussion on Alzheimer\\'s disease (AD) argues that it presents in part a disconnection syndrome. Studies using functional magnetic resonance imaging, positron emission tomography and electroencephalography demonstrate that synchronicity of brain activity is altered in AD and correlates with cognitive deficits. Moreover, recent advances in diffusion tensor imaging have made it possible to track axonal projections across the brain, revealing substantial regional impairment in fiber-tract integrity in AD. Accumulating evidence points towards a network breakdown reflecting disconnection at both the structural and functional system level. The exact relationship among these multiple mechanistic variables and their contribution to cognitive alterations and ultimately decline is yet unknown. Focused research efforts aimed at the integration of both function and structure hold great promise not only in improving our understanding of cognition but also of its characteristic progressive metamorphosis in complex chronic neurodegenerative disorders such as AD.

  2. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Tour - Deutsch (German) Alzheimer's Association Hindi (हिन्दी) Alzheimer's Disease हिन्दी (Hindi) Bilingual PDF Health Information Translations Italian (italiano) Inside the Brain: An Interactive ...

  3. Cognitive aging and Alzheimer's disease

    OpenAIRE

    Vandenberghe, R; Tournoy, J.

    2005-01-01

    Cognitive aging and clinically probable Alzheimer's disease can be discriminated by means of clinical and neuropsychological testing, and structural and functional imaging techniques. Research at the level of cognitive brain systems and at the molecular level provides exciting new insights into the relation between aging and neurodegeneration. The advances at the clinical and at the basic research levels are necessary if we wish to meet the formidable challenge that the increasing prevalence ...

  4. Alzheimer's Disease and Vitamin E

    OpenAIRE

    Empey, Matthew

    1998-01-01

    Alzheimer's disease (AD) is a form of dementia characterized by generalized and progressive cognitive dysfunction. Research has determined that an important pathological component of AD is neuronal damage and death in certain brain regions precipitated by oxidative damage. This paper reviews the pathology of AD, describes the biochemical processes pertaining to oxidative stress and antioxidant compounds, and reviews the evidence that one particular antioxidant, vitamin E, may be effective in ...

  5. The role of SPECT in the diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

    Alzheimer's disease is a widespread debilitating neurological disorder which normally affects people in their later life. The personal and financial impact of this disease on patients and their families is enormous, with round-the-clock care being required for those severely affected. There is no single test available to diagnose the disease and, at this time, diagnosis is by a process of elimination. The author considers that neuroimaging has played an important role to this effect, and the use of single photon emission computed tomography (SPECT) is playing an increasing part in helping to eliminate other forms of dementia which may cause similar symptoms to Alzheimer's. It is expected that the relative availability and low cost of SPECT would make it the imaging method of choice in the future. 11 refs., tabs., figs

  6. Magnetic resonance imaging of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lehericy, Stephane [Universite Pierre et Marie Curie-Paris 6, Department of Neuroradiology, Paris, Cedex 13 (France); Universite Pierre et Marie Curie-Paris 6, Inserm U610, Paris, Cedex 13 (France); Marjanska, Malgorzata [University of Minnesota, Center for Magnetic Resonance Research and Department of Radiology, Minneapolis, MN (United States); Mesrob, Lilia; Kinkingnehun, Serge [Universite Pierre et Marie Curie-Paris 6, Inserm U610, Paris, Cedex 13 (France); Sarazin, Marie [Universite Pierre et Marie Curie-Paris 6, Department of Neurology, Paris, Cedex 13 (France)

    2007-02-15

    A modern challenge for neuroimaging techniques is to contribute to the early diagnosis of neurodegenerative diseases, such as Alzheimer's disease (AD). Early diagnosis includes recognition of pre-demented conditions, such as mild cognitive impairment (MCI) or having a high risk of developing AD. The role of neuroimaging therefore extends beyond its traditional role of excluding other conditions such as neurosurgical lesions. In addition, early diagnosis would allow early treatment using currently available therapies or new therapies in the future. Structural imaging can detect and follow the time course of subtle brain atrophy as a surrogate marker for pathological processes. New MR techniques and image analysis software can detect subtle brain microstructural, perfusion or metabolic changes that provide new tools to study the pathological processes and detect pre-demented conditions. This review focuses on markers of macro- and microstructural, perfusion, diffusion and metabolic MR imaging and spectroscopy in AD. (orig.)

  7. Imaging the earliest stages of Alzheimer's disease.

    Science.gov (United States)

    Wu, William; Small, Scott A

    2006-12-01

    Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer' disease in living people. The earliest stage of Alzheimer's disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, 'functional' imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of 'function' and then review the different approaches that measure brain dysfunction in Alzheimer' disease.

  8. Recent progress of PET in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Na NIU

    2014-03-01

    Full Text Available Alzheimer's disease is the most common cause of dementia in the current elderly population. PET can detect pathophysiological changes in Alzheimer's disease with different radiotracers. This paper will focus on evaluating the value of 18F-FDG, amyloid and tau protein PET imaging in Alzheimer's disease. PET has been demonstrated to play an important role in the research of etiology, early diagnosis, differential dignosis, prognosis and medical treatment of Alzheimer's disease. doi: 10.3969/j.issn.1672-6731.2014.03.007

  9. Neurobiology of apathy in Alzheimer's disease Neurobiologia da apatia na doença de Alzheimer

    Directory of Open Access Journals (Sweden)

    Henrique Cerqueira Guimarães

    2008-06-01

    Full Text Available Apathy is considered the most frequent neuropsychiatric disturbance in dementia and its outcome is generally deleterious. Apathy can be related to a dysfunction of the anatomical-system that supports the generation of voluntary actions, namely the prefrontal cortex and/or the prefrontal-subcortical circuits. In Alzheimer's disease, pathological and neuroimaging data indicate that apathy is likely due to a dysfunction of the medial prefrontal cortex. Accordingly, in this review article, we propose a pathophysiological model to explain apathetic behavior in Alzheimer's disease, combining data from neuroimaging, neuropathology and experimental research on the role of orbito-frontal cortex, anterior cingulate cortex, basal ganglia and dopamine in decision-making neurobiology.Apatia é considerada a alteração neuropsiquiátrica mais freqüente nas demências e suas conseqüências são habitualmente deletérias. Apatia pode ser relacionada à disfunção do sistema anatômico responsável pela geração de ações voluntárias, conhecido com córtex pré-frontal e/ou circuitos pré-frontais-subcorticais. Na doença de Alzheimer, evidências neuropatológicas e de neuroimagem funcional indicam que a apatia é provavelmente decorrente da disfunção do córtex pré-frontal medial. Assim, neste artigo de revisão, apresentamos uma proposta de um modelo fisiopatológico para explicar o comportamento apático na doença de Alzheimer, combinando dados de neuropatologia, neuroimagem e experimentação animal sobre o papel do córtex órbito-frontal, cíngulo anterior, núcleos da base e dopamina na neurobiologia da tomada de decisão.

  10. Study on Alzheimer's disease model

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is well known that the main brain lesion in Alzheimer's disease (AD) brain is neurofibrillary tangles (NFT) and senile plaques (SP). The amount of NFT is positively correlated with clinical degree of dementia in AD. It is also well studied that the major component of NFT is abnormally hyperphosphorylated microtubule associated protein tau that is caused by an imbalance of protein kinase and protein phosphatase (PP). To reconstitute a specific AD model based on the above hypothesis, we have injected separately calcium calmodulin dependent protein kinase (CaMKKII) activator, bradykinin and PP-2B inhibitor, cyclosporin A into rat hippocampus in the present study. The results showed that the injection of bradykinin caused learning and memory deficient in rats as well as Alzheimer-like tau phosphorylation, including Ser-262/356, Thr-231/235 and Ser-396/404. On the other hand, the injection of cyclosporin A induced the same phosphorylation sites as above except Ser-262/356, however, it did not mimic rat behavior abnormality as bradykinin injection did. The data suggested that activating of CaMKII and the phosphorylation of Ser-262/356 at tau might responsible for the lesion of learning and memory in our model rats. We also incubated PP-2A and PP-1 inhibitor, okadaic acid with human neuroblastoma cell line (SH-SY5Y), and found that (1) inhibition of above PPs induced Alzheimer-like phosphorylation and accumulation of neurofilaments, and Alzheimer-like microtubule disruption, (2) melatonin showed certain protection of the cell from okadaic acid toxicity. The data obtained from this study is significant in AD specific model study.

  11. Quiz: Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... How many Americans over age 65 may have Alzheimer's disease? as many as 5 million as many ...

  12. Recent developments in Alzheimer's disease therapeutics

    Directory of Open Access Journals (Sweden)

    Aisen Paul S

    2009-02-01

    Full Text Available Abstract Alzheimer's disease is a devastating neurological disorder that affects more than 37 million people worldwide. The economic burden of Alzheimer's disease is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least $100 billion. Current FDA-approved drugs for Alzheimer's disease do not prevent or reverse the disease, and provide only modest symptomatic benefits. Driven by the clear unmet medical need and a growing understanding of the molecular pathophysiology of Alzheimer's disease, the number of agents in development has increased dramatically in recent years. Truly *disease-modifying' therapies that target the underlying mechanisms of Alzheimer's disease have now reached late stages of human clinical trials. Primary targets include beta-amyloid, whose presence and accumulation in the brain is thought to contribute to the development of Alzheimer's disease, and tau protein which, when hyperphosphorylated, results in the self-assembly of tangles of paired helical filaments also believed to be involved in the pathogenesis of Alzheimer's disease. In this review, we briefly discuss the current status of Alzheimer's disease therapies under study, as well the scientific context in which they have been developed.

  13. Applications of Neuroimaging to Disease-Modification Trials in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Adam S. Fleisher

    2009-01-01

    Full Text Available Critical to development of new therapies for Alzheimer’s disease (AD is the ability to detect clinical or pathological change over time. Clinical outcome measures typically used in therapeutic trials have unfortunately proven to be relatively variable and somewhat insensitive to change in this slowly progressive disease. For this reason, development of surrogate biomarkers that identify significant disease-associated brain changes are necessary to expedite treatment development in AD. Since AD pathology is present in the brain many years prior to clinical manifestation, ideally we want to develop biomarkers of disease that identify abnormal brain structure or function even prior to cognitive decline. Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new amyloid imaging techniques, and spinal fluid markers of AD all have great potential to provide surrogate endpoint measures for AD pathology. The Alzheimer’s disease neuroimaging initiative (ADNI was developed for the distinct purpose of evaluating surrogate biomarkers for drug development in AD. Recent evidence from ADNI demonstrates that imaging may provide more sensitive, and earlier, measures of disease progression than traditional clinical measures for powering clinical drug trials in Alzheimer's disease. This review discusses recently presented data from the ADNI dataset, and the importance of imaging in the future of drug development in AD.

  14. Maternal Transmission of Alzheimer Disease

    OpenAIRE

    Heggeli, Kristin; Crook, Julia; Thomas, Colleen; Graff-Radford, Neill

    2012-01-01

    Some propose maternal Alzheimer disease (1) inheritance. We compared dementia family histories in AD cases and cognitively normal controls. We expected more mothers to have AD in both groups. If maternal risk was not only due to female longevity more AD cases’ than controls’ mothers should be demented. We matched 196 AD cases to 200 controls by gender and age. We obtained parent dementia status and age of death for 348 AD and 319 control parents. 24 (12%) controls’ fathers, 26 (13%) AD patien...

  15. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  16. Turning principles into practice in Alzheimer's disease

    NARCIS (Netherlands)

    Lindesay, J.; Bullock, R.; Daniels, H.; Emre, M.; Foerstl, H.; Froelich, L.; Gabryelewicz, T.; Martinez-Lage, P.; Monsch, A. U.; Tsolaki, M.; van Laar, T.

    2010-01-01

    P>The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer's Disease International (ADI) launched a Global Alzheimer's Disease

  17. Estrogen and early-onset Alzheimer's disease

    NARCIS (Netherlands)

    A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cock); J.C.M. Witteman (Jacqueline)

    1999-01-01

    textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of re

  18. Alzheimer disease: presenilin springs a leak

    OpenAIRE

    Gandy, S; Doeven, M.K.; Poolman, B.

    2006-01-01

    Presenilins are thought to contribute to Alzheimer disease through a protein cleavage reaction that produces neurotoxic amyloid-beta peptides. A new function for presenilins now comes to light - controlling the leakage of calcium out of the endoplasmic reticulum. Is this a serious challenge to the 'amyloid hypothesis' of Alzheimer disease?

  19. The Importance of Adipokines in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seyid Ahmet Ay

    2015-06-01

    Full Text Available Dementia and Alzheimers disease are characterized by disturbances in brain function and structure. Similarly, body mass index and obesity are associated with certain brain pathologies, including Alzheimers disease and dementia. In fact, there is mounting evidence linking metabolic dysfunction with dementia and Alzheimers disease. Major endocrine axes constitute links between brain and peripheral tissues, especially adipose tissue. Adipose tissue is metabolically very active and produces a variety of adipokines known to affect both peripheral and central nervous system processes. Experimental studies suggest that changes in adipokine function may contribute to the pathogenesis of Alzheimers disease. Herein, we review the adipokines leptin and adiponectin which are associated with morbidities related to obesity as well as dementia and Alzheimers disease. [Dis Mol Med 2015; 3(2.000: 22-28

  20. MRI morphometry in Alzheimer's disease.

    Science.gov (United States)

    Matsuda, Hiroshi

    2016-09-01

    MRI based evaluation of brain atrophy is regarded as a valid method to stage the disease and to assess progression in Alzheimer's disease (AD). Volumetric software programs have made it possible to quantify gray matter in the human brain in an automated fashion. At present, voxel based morphometry (VBM) is easily applicable to the routine clinical procedure with a short execution time. The importance of the VBM approach is that it is not biased to one particular structure and is able to assess anatomical differences throughout the brain. Stand-alone VBM software running on Windows, Voxel-based Specific Regional analysis system for AD (VSRAD), has been widely used in the clinical diagnosis of AD in Japan. On the other hand, recent application of graph theory to MRI has made it possible to analyze changes in structural connectivity in AD.

  1. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease 7 Warning Signs of Alzheimer's Past Issues / Fall 2010 Table of Contents The ... Suncoast Gerontology Center, University of South Florida. How Alzheimer's Changes the Brain The only definite way to ...

  2. Exploring Biomarkers for Alzheimer's Disease.

    Science.gov (United States)

    Sharma, Neeti; Singh, Anshika Nikita

    2016-07-01

    Alzheimer's Disease (AD) is one of the most common form of dementia occurring in elderly population worldwide. Currently Aβ42, tau and p-tau in the cerebrospinal fluid is estimated for confirmation of AD. CSF which is being used as the potent source for biomarker screening is obtained by invasive lumbar punctures. Thus, there is an urgent need of minimal invasive methods for identification of diagnostic markers for early detection of AD. Blood serum and plasma serves as an appropriate source, due to minimal discomfort to the patients, promoting frequent testing, better follow-up and better consent to clinical trials. Hence, the need of the hour demands discovery of diagnostic and prognostic patient specific signature biomarkers by using emerging technologies of mass spectrometry, microarrays and peptidomics. In this review we summarize the present scenario of AD biomarkers such as circulatory biomarkers, blood based amyloid markers, inflammatory markers and oxidative stress markers being investigated and also some of the potent biomarkers which might be able to predict early onset of Alzheimer's and delay cognitive impairment. PMID:27630867

  3. 2008 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2008-03-01

    Alzheimer's disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer's disease. Every 71 seconds someone in America develops Alzheimer's disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer's disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer's disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer's disease. This report provides information to increase understanding of the public health impact of Alzheimer's disease, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. PMID:18631956

  4. Harmonized diagnostic criteria for Alzheimer's disease

    DEFF Research Database (Denmark)

    Morris, J C; Blennow, K; Froelich, L;

    2014-01-01

    BACKGROUND: Two major sets of criteria for the clinical diagnosis of Alzheimer's disease (AD) recently have been published, one from an International Working Group (IWG) and the other from working groups convened by the National Institute on Aging (NIA) and the Alzheimer's Association (AA...

  5. Alzheimer's disease is incurable but preventable.

    Science.gov (United States)

    de la Torre, Jack C

    2010-01-01

    The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment. PMID:20182017

  6. Quantitative evaluation of Alzheimer's disease

    Science.gov (United States)

    Duchesne, S.; Frisoni, G. B.

    2009-02-01

    We propose a single, quantitative metric called the disease evaluation factor (DEF) and assess its efficiency at estimating disease burden in normal, control subjects (CTRL) and probable Alzheimer's disease (AD) patients. The study group consisted in 75 patients with a diagnosis of probable AD and 75 age-matched normal CTRL without neurological or neuropsychological deficit. We calculated a reference eigenspace of MRI appearance from reference data, in which our CTRL and probable AD subjects were projected. We then calculated the multi-dimensional hyperplane separating the CTRL and probable AD groups. The DEF was estimated via a multidimensional weighted distance of eigencoordinates for a given subject and the CTRL group mean, along salient principal components forming the separating hyperplane. We used quantile plots, Kolmogorov-Smirnov and χ2 tests to compare the DEF values and test that their distribution was normal. We used a linear discriminant test to separate CTRL from probable AD based on the DEF factor, and reached an accuracy of 87%. A quantitative biomarker in AD would act as an important surrogate marker of disease status and progression.

  7. Advances in the study of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Angue Nkoghe Francoise; Yunman Li

    2005-01-01

    Alzheimer's disease (AD) is the most common cause of dementia, and the only treatment currently available for the disease is acetylcholinesterase inhibitors. Recent progress in understanding the molecular and cellular pathophysiology of Alzheimer's disease has suggested possible pharmacological interventions, including acetylcholineseterase inhibitors; secretase inhibitors; cholesterol lowering drugs; metal chelators and amyloid immunization. The objective of this paper is to review the main drugs possibly used for AD and their future therapeutic effects.

  8. The economic costs of Alzheimer's disease.

    Science.gov (United States)

    Hay, J W; Ernst, R L

    1987-09-01

    This paper estimates the economic costs of Alzheimer's Disease to individuals and to society, based on review of published Alzheimer's Disease-related research. The analysis is derived from epidemiological projections and cost information for the United States population in 1983. Estimated costs include both direct medical care and social support costs, as well as indirect costs, such as support services provided by family or volunteers, and the value of lost economic productivity in Alzheimer's Disease patients. Mid-range estimates of net annual expected costs for an Alzheimer's Disease patient, excluding the value of lost productivity, are $18,517 in the first year and $17,643 in subsequent years, with direct medical and social services comprising about half of these costs. Under base case assumptions, the total cost of disease per patient in 1983, was $48,544 to $493,277, depending upon patient's age at disease onset. The estimated present value of total net costs to society for all persons first diagnosed with Alzheimer's Disease in 1983 was $27.9-31.2 billion. Development of a public or private insurance market for the economic burdens of Alzheimer's Disease would fill some of the gaps in the current US system of financing long-term chronic disease care.

  9. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza

    2014-03-01

    Full Text Available The challenges for establishing an early diagnosis of Alzheimer’s disease (AD have created a need for biomarkers that reflect the core pathology of the disease. The cerebrospinal fluid (CSF levels of total Tau (T-tau, phosphorylated Tau (P-Tau and beta-amyloid peptide (Aβ42 reflect, respectively, neurofibrillary tangle and amyloid pathologies and are considered as surrogate markers of AD pathophysiology. The combination of low Aβ42 and high levels of T-tau and P-Tau can accurately identify patients with AD at early stages, even before the development of dementia. The combined analysis of the CSF biomarkers is also helpful for the differential diagnosis between AD and other degenerative dementias. The development of these CSF biomarkers has evolved to a novel diagnostic definition of the disease. The identification of a specific clinical phenotype combined with the in vivo evidence of pathophysiological markers offers the possibility to make a diagnosis of AD before the dementia stage with high specificity.

  10. Synaptic changes in Alzheimer's disease in vivo

    International Nuclear Information System (INIS)

    The article describes the current knowledge on biochemical changes in Alzheimer's disease. Following a summary on post mortem findings, results from positron emission tomography will be focused on. This synopsis shows that patients with Alzheimer's disease show very consistently changes in the cholinergic transmission. In addition to this, changes of the dopaminergic, noradrenergic and serotonergic system are observed. It is possible, that clinical, pathological and functional differences in Alzheimer's disease between different patients reflect variations of a single disease process. It is also thinkable, that there are subclassifications in Alzheimer's disease which are reflected in the above described biochemical abnormalities. In this case it is important in therapeutical terms to investigate these subtypes. (orig.)

  11. Alzheimer's disease: early diagnosis and treatment.

    Science.gov (United States)

    Chu, L W

    2012-06-01

    With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non-pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future. PMID:22665688

  12. Differential diagnosis of Alzheimer-type dementia and vascular dementia based on neuroimaging study

    International Nuclear Information System (INIS)

    A new method for differential diagnosis of Alzheimer-type dementia (AD) and vascular dementia (VD) based on neuroimaging studies was developed by Hayashi's quantification theory II. Fifty-five patients with AD and 36 patients with VD underwent both SPECT and MRI studies. Both images in each subject were scored according to the extent of hypoperfusion in areas including frontal and temporoparietal regions and the severity of deep white matter lesions and medial temporal lobe atrophy. The scores of AD and VD patients were significantly different, and this difference was considered to contribute most to the differential diagnosis of AD and VD. The weight of each score of SPECT and MRI items was computed, and the sum of the weights was calculated as a score for each subject to best distinguish AD from VD patients. This method was designed to simplify the calculation of the sample scores, and the sum of the weights was established so that a positive score (0≤) indicated the probability of AD, while a negative score (<0) indicated the probability of VD. The correct diagnosis rate was 91% (50/55) for AD and 89% (32/36) for VD, for an overall discrimination of 90%. The present method seemed to be practically useful in the differential diagnosis of AD and VD. (author)

  13. Lithium May Fend off Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 夏红

    2004-01-01

    @@ Lithium, a common treatment for manic depression, might also help to stave off②Alzheimer's disease. Patients who take the drug to stabilize their mood disorder are less likely to succumb to dementia③, a study reveals.

  14. Dementia (Including Alzheimer Disease) (Beyond the Basics)

    Science.gov (United States)

    ... Patient information: Tips for caregivers of people with Alzheimer disease (The Basics) Patient information: Mild cognitive impairment (The Basics) Patient information: Evaluating memory and thinking problems (The Basics) Patient information: Vitamin B12 deficiency and folate (folic acid) deficiency (The ...

  15. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

    Letenneur, L; Launer, L J; Andersen, K;

    2000-01-01

    The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow......-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (...), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28...

  16. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    Science.gov (United States)

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  17. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Mark Ide

    Full Text Available Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  18. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    Science.gov (United States)

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation. PMID:26963387

  19. Nuclear microscopy in Alzheimer's disease

    International Nuclear Information System (INIS)

    The elemental composition of the two types of brain lesions which characterise Alzheimer's disease (AD) has been the subject of intense scrutiny over the last decade, ever since it was proposed that inorganic trace elements, particularly aluminium, might be implicated in the pathogenesis of the disease. The major evidence for this involvement was the detection of aluminium in the characteristic lesions of the AD brain; neuritic plaques and neurofibrillary tangles (NFTs). Using the powerful combination of Particle-Induced X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and Scanning Transmission Ion Microscopy (STIM), it is possible to image and analyse structures in brain sections without recourse to chemical staining. Previous results on elemental composition of senile plaques indicated the absence of aluminium at the 15 parts per million level. We have more recently focused on the analysis of neurofibrillary tangles (NFTs), destructive structural defects within neurons. Imaging and analysis of neurons in brain tissue presented a greater challenge due to the small dimensional size compared with the plaques. We describe the methodology and the results of imaging and analysing neurons in brain tissue sections using Nuclear Microscopy. Our results show that aluminium is not present in either neurons or surrounding tissue in unstained sections at the 20 ppm level, but can be observed in stained sections. We also report elemental concentrations showing significant elevations of phosphorus, sulphur, chlorine, iron and zinc

  20. Medical foods for Alzheimer's disease.

    Science.gov (United States)

    Shah, Raj C

    2011-06-01

    Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary foodstuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better understanding of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65

  1. Multi-Channel neurodegenerative pattern analysis and its application in Alzheimer's disease characterization.

    Science.gov (United States)

    Liu, Sidong; Cai, Weidong; Wen, Lingfeng; Feng, David Dagan; Pujol, Sonia; Kikinis, Ron; Fulham, Michael J; Eberl, Stefan

    2014-09-01

    Neuroimaging has played an important role in non-invasive diagnosis and differentiation of neurodegenerative disorders, such as Alzheimer's disease and Mild Cognitive Impairment. Various features have been extracted from the neuroimaging data to characterize the disorders, and these features can be roughly divided into global and local features. Recent studies show a tendency of using local features in disease characterization, since they are capable of identifying the subtle disease-specific patterns associated with the effects of the disease on human brain. However, problems arise if the neuroimaging database involved multiple disorders or progressive disorders, as disorders of different types or at different progressive stages might exhibit different degenerative patterns. It is difficult for the researchers to reach consensus on what brain regions could effectively distinguish multiple disorders or multiple progression stages. In this study we proposed a Multi-Channel pattern analysis approach to identify the most discriminative local brain metabolism features for neurodegenerative disorder characterization. We compared our method to global methods and other pattern analysis methods based on clinical expertise or statistics tests. The preliminary results suggested that the proposed Multi-Channel pattern analysis method outperformed other approaches in Alzheimer's disease characterization, and meanwhile provided important insights into the underlying pathology of Alzheimer's disease and Mild Cognitive Impairment.

  2. 2016 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2016-04-01

    This report describes the public health impact of Alzheimer's disease, including incidence and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. It also examines in detail the financial impact of Alzheimer's on families, including annual costs to families and the difficult decisions families must often make to pay those costs. An estimated 5.4 million Americans have Alzheimer's disease. By mid-century, the number of people living with Alzheimer's disease in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer's disease every 66 seconds. By 2050, one new case of Alzheimer's is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2013, official death certificates recorded 84,767 deaths from Alzheimer's disease, making it the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age ≥ 65 years. Between 2000 and 2013, deaths resulting from stroke, heart disease, and prostate cancer decreased 23%, 14%, and 11%, respectively, whereas deaths from Alzheimer's disease increased 71%. The actual number of deaths to which Alzheimer's disease contributes is likely much larger than the number of deaths from Alzheimer's disease recorded on death certificates. In 2016, an estimated 700,000 Americans age ≥ 65 years will die with Alzheimer's disease, and many of them will die because of the complications caused by Alzheimer's disease. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. Average per-person Medicare payments for services to beneficiaries age ≥ 65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all

  3. The burden of Alzheimer's disease.

    Science.gov (United States)

    Burns, Alistair

    2000-07-01

    Alzheimer's disease (AD) imposes a severe burden upon patients and their carers. In particular, family carers of AD patients face extreme hardship and distress that represents a major but often hidden burden on healthcare systems. Carers often experience clinically significant alterations in physical and mental health, particularly depression. A number of individual features of the dementia syndrome that are known to be particularly burdensome to carers include the degree of cognitive impairment, amount of help required with activities of daily living, personality changes and the presence of psychiatric symptoms and behavioural disturbances. The neuropsychiatric features of AD patients can adversely impact the relationship between the patient and caregiver generating feelings of strain, burden and social isolation. Individual characteristics of the caregiver including personality, gender, degree of formal and informal support and physical and mental health, as well as attributional style ('coping style') and expressed emotion (critical or hostile attitudes), also dictate carer burden. As informal caregivers play such a crucial role in the care of AD patients, appropriate management strategies that incorporate interventions which address the specific burdens of the individual caregiver are essential. Reducing the burden of care can be achieved by the combination of a number of individual and general measures, including education, respite and emotion-focused interventions. These measures, accompanied by non-pharmacological strategies, are extremely important in the total care of the AD patient, with the emphasis on maintaining people in the community as long as possible.

  4. An anemia of Alzheimer's disease.

    Science.gov (United States)

    Faux, N G; Rembach, A; Wiley, J; Ellis, K A; Ames, D; Fowler, C J; Martins, R N; Pertile, K K; Rumble, R L; Trounson, B; Masters, C L; Bush, A I

    2014-11-01

    Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline. PMID:24419041

  5. Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Gu; Han-Chang Huang; Zhao-Feng Jiang

    2012-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder.The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau,as well as neuronal loss in specific brain regions.Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease.Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ,accumulation of which might interfere with the homeostasis of cellular metabolism.Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis.Mitochondrial dysfunction might contribute to Aβ neurotoxicity.In this review,we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

  6. Alzheimer's Disease: An Exacerbation of Senile Phenoptosis.

    Science.gov (United States)

    Isaev, N K; Stelmashook, E V; Genrikhs, E E; Oborina, M V; Kapkaeva, M R; Skulachev, V P

    2015-12-01

    Alzheimer's disease is characterized by progressive memory loss and cognitive decline accompanied by degeneration of neuronal synapses, massive loss of neurons in the brain, eventually resulting in complete degradation of personality and death. Currently, the cause of the disease is not fully understood, but it is believed that the person's age is the major risk factor for development of Alzheimer's disease. People who have survived after cerebral stroke or traumatic brain injury have substantially increased risk of developing Alzheimer's disease. Social exclusion, low social activity, physical inactivity, poor mental performance, and low level of education are among risk factors for development of this neurodegenerative disease, which is consistent with the concept of phenoptosis (Skulachev, V. P., et al. (1999) Biochemistry (Moscow), 64, 1418-1426; Skulachev, M. V., and Skulachev, V. P. (2014) Biochemistry (Moscow), 79, 977-993) stating that rate of aging is related to psychological and social aspects in human behavior. Here we assumed that Alzheimer's disease might be considered as an exacerbation of senile phenoptosis. If so, then development of this disease could be slowed using mitochondria-targeted antioxidants due to the accumulated data demonstrating a link between mitochondrial dysfunction and oxidative stress both with normal aging and Alzheimer's disease. PMID:26638682

  7. Stem cell treatment for Alzheimer's disease.

    Science.gov (United States)

    Li, Ming; Guo, Kequan; Ikehara, Susumu

    2014-10-23

    Alzheimer's disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.

  8. Alzheimer's disease due to loss of function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses. The amy......Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses...

  9. Diagnosis and treatment of Alzheimer's disease

    International Nuclear Information System (INIS)

    Alzheimer's disease is often diagnosed too late. Its etiology is still largely unknown and remains one of the big challenges in neurobiological fundamental research. Optimized early and differential diagnosis can be ensured by a dynamic concept of multidisciplinary diagnosis in cooperation between practitioners specializing in brain disorders, clinical psychogeriatric deprtments, and general practitioners. This, in turn, will enable individualized planning of further living conditions and care of Alzheimer patients and their relations as well as efficient and early pharmacotherapy and psychological intervention. (orig)

  10. Imaging markers for Alzheimer disease

    Science.gov (United States)

    Bocchetta, Martina; Chételat, Gael; Rabinovici, Gil D.; de Leon, Mony J.; Kaye, Jeffrey; Reiman, Eric M.; Scheltens, Philip; Barkhof, Frederik; Black, Sandra E.; Brooks, David J.; Carrillo, Maria C.; Fox, Nick C.; Herholz, Karl; Nordberg, Agneta; Jack, Clifford R.; Jagust, William J.; Johnson, Keith A.; Rowe, Christopher C.; Sperling, Reisa A.; Thies, William; Wahlund, Lars-Olof; Weiner, Michael W.; Pasqualetti, Patrizio; DeCarli, Charles

    2013-01-01

    Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials. PMID:23897875

  11. Use of acetylcholinesterase inhibitors in Alzheimer's disease.

    Science.gov (United States)

    Moghul, S; Wilkinson, D

    2001-09-01

    Alzheimer's disease is a growing problem in an aging Western world, estimated to have cost the US economy USD 1.75 trillion. Until recently, the management of Alzheimer's disease largely comprised support for the family, nursing care and the use of unlicensed medication to control behavioral disturbances. The three new acetylcholinesterase inhibitors licensed to treat Alzheimer's disease (donepezil, rivastigmine and galantamine) have provided clinicians with a major impetus to their desire to diagnose and treat this lethal disease. Their effects on cognition are proven. More recent work on the effects of acetylcholinesterase inhibitors on behavioral symptoms, activities of daily living and caregiver burden have also been encouraging. Emerging work indicates their likely efficacy in other dementias (e.g., vascular dementia, dementia with Lewy bodies). This review summarizes the evidence concerning the impact of acetylcholinesterase inhibitors in dementia both currently and over the next 5 years. PMID:19811047

  12. Biomarkers of Alzheimer's Disease: From Central Nervous System to Periphery?

    Directory of Open Access Journals (Sweden)

    Enrico Mossello

    2011-01-01

    Full Text Available Alzheimer's Disease (AD is the most frequent form of dementia and represents one of the main causes of disability among older subjects. Up to now, the diagnosis of AD has been made according to clinical criteria. However, the use of such criteria does not allow an early diagnosis, as pathological alterations may be apparent many years before the clear-cut clinical picture. An early diagnosis is even more valuable to develop new treatments, potentially interfering with the pathogenetic process. During the last decade, several neuroimaging and cerebrospinal fluid (CSF parameters have been introduced to allow an early and accurate detection of AD patients, and, recently, they have been included among research criteria for AD diagnosis. However, their use in clinical practice suffers from limitations both in accuracy and availability. The increasing amount of knowledge about peripheral biomarkers will possibly allow the future identification of reliable and easily available diagnostic tests.

  13. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    Science.gov (United States)

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  14. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010

    Science.gov (United States)

    2010-11-04

    ... terrible disease. As we continue our fight against Alzheimer's disease, we must seek new ways to prevent... and attention to those facing Alzheimer's disease. Until we find more effective treatments and a cure... Documents#0;#0; ] Proclamation 8591 of October 29, 2010 National Alzheimer's Disease Awareness Month,...

  15. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

    J.J.M. Hoozemans; A.J.M. Rozemuller; E.S. van Haastert; P. Eikelenboom; W.A. van Gool

    2011-01-01

    ABSTRACT: BACKGROUND: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between

  16. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... is important for the brain to function well. Alzheimer's disease disrupts this intricate interplay. By compromising the ability ... of the brain changes that take place in Alzheimer's disease. Abnormal structures called beta amyloid plaques and neurofibrillary ...

  17. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... is important for the brain to function well. Alzheimer's disease disrupts this intricate interplay. By compromising the ... of the brain changes that take place in Alzheimer's disease. Abnormal structures called beta amyloid plaques and ...

  18. Dietary intake of antioxidants and risk of Alzheimer disease

    NARCIS (Netherlands)

    M.J. Engelhart (Marianne); M.I. Geerlings (Miriam); A. Ruitenberg (Annemieke); J.C. van Swieten; J.C.M. Witteman (Jacqueline); M.M.B. Breteler (Monique); A. Hofman (Albert)

    2002-01-01

    textabstractCONTEXT: Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress. OB

  19. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... disease over time destroys memory and thinking skills. Scientific research has revealed some of the brain changes that ... Alzheimer's disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's ...

  20. Verbal fluency in Alzheimer's disease, Parkinson's disease, and major depression

    Directory of Open Access Journals (Sweden)

    Narahyana Bom de Araujo

    2011-01-01

    Full Text Available OBJECTIVE: To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity. METHODS: Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals. We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model. RESULTS: The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34 than in patients with major depression (n = 52 or Parkinson's disease (n = 17 (p<0.001. The average number of words listed was much lower for Alzheimer's disease patients (7.2 words compared to the patients presenting with major depression (14.6 words or Parkinson's disease (15.7 words (KW test = 32.4; p<0.01. Major depression and Parkinson's disease groups listed 44% (ROM = 1.44 and 48% (ROM = 1.48 more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74 reduction in the number of words listed when compared to mild cases. CONCLUSIONS: Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages.

  1. NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers.

    Science.gov (United States)

    Vos, Stephanie J B; Gordon, Brian A; Su, Yi; Visser, Pieter Jelle; Holtzman, David M; Morris, John C; Fagan, Anne M; Benzinger, Tammie L S

    2016-08-01

    The National Institute of Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and positron emission tomography imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural magnetic resonance imaging) with longitudinal clinical follow-up. Participants were classified in preclinical AD stage 1 (β-amyloidosis) or preclinical AD stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based on neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury and has important implications for clinical trials using biomarkers for enrollment or as surrogate end point measures. PMID:27318129

  2. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

    Science.gov (United States)

    2011-11-04

    ... Documents#0;#0; ] Proclamation 8745 of November 1, 2011 National Alzheimer's Disease Awareness Month, 2011... heartbreak of watching a loved one struggle with Alzheimer's disease is a pain they know all too well. Alzheimer's disease burdens an increasing number of our Nation's elders and their families, and it...

  3. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012

    Science.gov (United States)

    2012-11-06

    ... Documents#0;#0; ] Proclamation 8897 of November 1, 2012 National Alzheimer's Disease Awareness Month, 2012... country confront the tragic realities of Alzheimer's disease--an irreversible, fatal illness that robs men... Americans grows in the coming years, Alzheimer's disease will continue to pose serious risks to our...

  4. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

    Science.gov (United States)

    2013-11-05

    ... Documents#0;#0; ] Proclamation 9050 of October 31, 2013 National Alzheimer's Disease Awareness Month, 2013 By the President of the United States of America A Proclamation Alzheimer's disease is an... younger Americans with early-onset Alzheimer's disease. This month, we stand with everyone confronting...

  5. Famous forgetters: notable people and Alzheimer's disease.

    Science.gov (United States)

    Jones, Jeffrey M; Jones, Joni L

    2010-03-01

    As life expectancy continues to increase, Alzheimer's disease (AD) has become much more prevalent and as yet there is no cure. This has given rise to the situation Tithonus faced in Greek mythology of living longer but not staying young. In this article, the authors explore this phenomenon while reviewing some notable people and AD. PMID:19949162

  6. Cannabinoids in late-onset Alzheimer's disease

    NARCIS (Netherlands)

    Ahmed, A.; Marck, M.A. van der; Elsen, G. van den; Olde Rikkert, M.G.M.

    2015-01-01

    Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicin

  7. Estrogen receptor beta treats Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Zhu Tian; Jia Fan; Yang Zhao; Sheng Bi; Lihui Si; Qun Liu

    2013-01-01

    In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid β protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer's disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA, tumor necrosis factor α mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in Alzheimer's disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on Alzheimer's disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hippocampus of Alzheimer's disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.

  8. Atorvastatin attenuates oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Cai Zhiyou; Yan Yong; Wang Yonglong

    2008-01-01

    Objective: To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, AchE and Acb in AD and its neuroprotection mechanisms. Methods Subjects were divided into: normal blood lipid level group with Alzheimer's disease (A), higher blood lipid level group with Alzheimer's disease (AH), normal blood lipid level Alzheimer's disease group with atorvastatin treeatment (AT),higher blood lipid level Alzheimer's disease group with atorvastatin treeatment(AHT). Ox-LDL was measured by enzyme linked immunosorbent assay; SOD, MDA, ox-LDL, AchE, Ach and blood lipid level in AD was measured by biochemistry. Results: The serum level of MDA, AchE in AH group after atorvastatin treatment is lower ;The serum level of SOD, Ach in AH group is more increased than that of in A group; The serum level of ox-LDL in AH, A groups is lower than that of in A group; The dementia degree is lower after atorvastatin treatment. Conclusion: Atorvastatin can decrease serum level of MDA, AchE and ox-LDL, and increase that of SOD, Acb, and attenuate dementia symptom in AD, especially, with hyperlipemia. The hypothesis of atorvastatin neuroprotection is concluded that atorvastatin may restrain free radical reaction and retard oxidation in AD.

  9. Alzheimer disease : presenilin springs a leak

    NARCIS (Netherlands)

    Gandy, S.; Doeven, M.K.; Poolman, B.

    2006-01-01

    Presenilins are thought to contribute to Alzheimer disease through a protein cleavage reaction that produces neurotoxic amyloid-beta peptides. A new function for presenilins now comes to light - controlling the leakage of calcium out of the endoplasmic reticulum. Is this a serious challenge to the '

  10. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

    De Deyn, P.P.; Drenth, Annemieke F. J.; Kremer, B.P.; Oude Voshaar, R.C.; Van Dam, D.

    2013-01-01

    Introduction: Psychosis is a common and difficult to treat symptom in Alzheimer's disease (AD). It is a cause of diminished quality of life and care-giver distress. Atypical antipsychotics are frequently used for the treatment of dementia-related psychosis, despite FDA warnings because of increased

  11. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla;

    2012-01-01

    PURPOSE: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). METHODS: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

  12. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L;

    2012-01-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North...

  13. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

    Deyn, P.P. de; Drenth, A.F.; Kremer, B.; Oude Voshaar, R.C.; Dam, D. Van

    2013-01-01

    INTRODUCTION: Psychosis is a common and difficult to treat symptom in Alzheimer's disease (AD). It is a cause of diminished quality of life and caregiver distress. Atypical antipsychotics are frequently used for the treatment of dementia-related psychosis, despite FDA warnings because of increased m

  14. Early psychosocial intervention in Alzheimer's disease

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Sørensen, Jan; Waldorff, Frans B;

    2014-01-01

    OBJECTIVE: To assess the cost utility of early psychosocial intervention for patients with Alzheimer's disease and their primary caregivers. DESIGN: Cost utility evaluation alongside a multicentre, randomised controlled trial with 3 years of follow-up. SETTING: Primary care and memory clinics...

  15. Hyperhomocysteinemia and Alzheimer's disease: A systematic review

    NARCIS (Netherlands)

    F. van Dam; W.A. van Gool

    2009-01-01

    Hyperhomocysteinemia (HHcy) is supposed to be one of the modifiable risk factors that, if treated, may delay the onset of Alzheimer's disease (AD). The relation between serum homocysteine (Hcy) and vitamin levels during AD and its preclinical phase was systematically reviewed. Searches through large

  16. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study

    OpenAIRE

    Richard, Edo; Ben A. Schmand; Eikelenboom, Piet; van Gool, Willem A.; ,

    2013-01-01

    Objectives To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. Design Diagnostic accuracy study in a multicentre prospective cohort study. Setting Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. Participants Patients with mild cognitive impairment (MCI; n=181) ...

  17. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study

    OpenAIRE

    E. Richard; Schmand, B.A.; Eikelenboom, P.; Gool, van, A.C.M.

    2013-01-01

    OBJECTIVES: To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. DESIGN: Diagnostic accuracy study in a multicentre prospective cohort study. SETTING: Alzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. PARTICIPANTS: Patients with mild cognitive impairment (MCI; n=1...

  18. Neuroimaging biomarkers for Parkinson disease: facts and fantasy.

    Science.gov (United States)

    Perlmutter, Joel S; Norris, Scott A

    2014-12-01

    In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. PMID:25363872

  19. Socio-economic Aspects of Alzheimer's Disease.

    Science.gov (United States)

    Marešová, Petra; Mohelská, Hana; Dolejš, Josef; Kuča, Kamil

    2015-01-01

    Social development, better living conditions and medical advances lead to the fact that more people have the opportunity to live longer than in the past. The aging population is a characteristic feature of demographic trends in developed countries. This trend is closely linked with the issue of increasing number of diseases in old age and increasing government expenditure on health and social care. The most frequently mentioned diseases in old age include dementia. The cause may lie in all kinds of diseases, the most common are Alzheimer's disease and cerebrovascular disease. Now the care of current 35 million patients with dementia costs over $ 600 billion per year, it is approximately one percent of global Gross Domestic Product. This review discusses the recent issues and questions in the area of social and economic aspects of Alzheimer's disease. It focuses in detail on the national strategies in the approach to Alzheimer's disease, the anticipated problems concerning the insufficient number of social workers and necessary expenses of state budgets in the future. The situation in the area of health insurance companies' expenditures is illustrated in the context of the analysis of long-term care systems, in the chosen countries within the European Union. PMID:26510983

  20. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

    Science.gov (United States)

    2012-02-24

    ... HUMAN SERVICES Draft National Plan To Address Alzheimer's Disease AGENCY: Office of the Assistant.... SUMMARY: HHS is soliciting public input on the draft National Plan to Address Alzheimer's Disease, which... . Background On January 4, 2011, President Barack Obama signed into law the National Alzheimer's Project...

  1. Adiposity, type 2 diabetes and Alzheimer's disease

    OpenAIRE

    Luchsinger, José A.; Gustafson, Deborah R

    2009-01-01

    This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies ha...

  2. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... Alzheimer's disease, but there is still much to learn. What other changes are taking place in the ... of Alzheimer's and related brain disorders As we learn more, researchers move ever closer to discovering ways ...

  3. [Truth telling of Alzheimer's disease diagnosis].

    Science.gov (United States)

    Fuentes R, Paola; Prato, Juan Andrés

    2012-06-01

    Alzheimer's disease is becoming an increasingly common problem due to population aging. Most of the research on truth telling in relation to diagnosis has been done in oncology. However, although growing, there has a lack of interest about attitudes held among physicians towards disclosing the diagnosis of Alzheimer's disease. Physicians, family caregivers and patients have different views about it. The reasons most often given for communicating the diagnosis are the right to know, relief of anxiety to know the cause of memory problems, early access to treatment and ability to plan ahead. On the contrary, the reasons for concealing the diagnosis are based on the right not to know, the anxiety associated to knowing the diagnosis and the absence of curative therapies for the disease. The aim of this paper is to report the current state of literature on diagnostic truth telling in dementia, review the ethical principles involved, and finally give a strategy to address the issue.

  4. Alzheimer's Disease at a Glance

    Science.gov (United States)

    ... R S T U V W X Y Z Alzheimer’s Disease at a Glance Share: On This Page ... health approaches for preventing or slowing dementia, including Alzheimer’s disease. Currently, there is no strong evidence that ...

  5. Alzheimer's disease: An acquired neurodegenerative laminopathy.

    Science.gov (United States)

    Frost, Bess

    2016-05-01

    The nucleus is typically depicted as a sphere encircled by a smooth surface of nuclear envelope. For most cell types, this depiction is accurate. In other cell types and in some pathological conditions, however, the smooth nuclear exterior is interrupted by tubular invaginations of the nuclear envelope, often referred to as a "nucleoplasmic reticulum," into the deep nuclear interior. We have recently reported a significant expansion of the nucleoplasmic reticulum in postmortem human Alzheimer's disease brain tissue. We found that dysfunction of the nucleoskeleton, a lamin-rich meshwork that coats the inner nuclear membrane and associated invaginations, is causal for Alzheimer's disease-related neurodegeneration in vivo. Additionally, we demonstrated that proper function of the nucleoskeleton is required for survival of adult neurons and maintaining genomic architecture. Here, we elaborate on the significance of these findings in regard to pathological states and physiological aging, and discuss cellular causes and consequences of nuclear envelope invagination. PMID:27167528

  6. Alzheimer's disease: synaptic dysfunction and Abeta

    LENUS (Irish Health Repository)

    Shankar, Ganesh M

    2009-11-23

    Abstract Synapse loss is an early and invariant feature of Alzheimer\\'s disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.

  7. Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, S. [Tokyo Univ. (Japan). Faculty of Medicine; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

    1996-12-31

    To investigate the cause of Alzheimer`s disease (senile dementia of Alzheimer`s disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer`s disease using heavy ion (5 MeV Si{sup 3+}) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si{sup 2+}) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer`s disease using 5 MeV Si{sup 3+} microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer`s disease is caused by accumulation of Al in the nuclei of brain cells. (author)

  8. Molecular regulators of neurogenesis in Alzheimer's disease

    OpenAIRE

    Crews, Leslie Anne

    2010-01-01

    Alzheimer's Disease (AD) is characterized by cognitive impairment, progressive neurodegeneration, and formation of amyloid-[Beta] (A[Beta])-containing plaques. These neuropathological features are accompanied by deregulation of signaling cascades such as the cyclin-dependent kinase- 5 (CDK5) pathway. Recent studies have revealed that neurodegeneration in AD is also associated with alterations in hippocampal neurogenesis, which may play a critical role in cognitive impairments and memory loss....

  9. Neurofibrillary pathology and aluminum in Alzheimer's disease

    OpenAIRE

    Shin, R. W.; Lee, V. M. Y; Trojanowski, J Q

    1995-01-01

    Since the first reports of aluminum-induced neurofibrillary degeneration in experimental animals, extensive studies have been performed to clarify the role played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional evidence implicating aluminum in AD includes elevated levels of aluminum in the AD brain, epidemiological data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathological lesions o...

  10. Adverse Stress, Hippocampal Networks, and Alzheimer's Disease

    OpenAIRE

    Rothman, Sarah M.; Mattson, Mark P.

    2009-01-01

    Recent clinical data have implicated chronic adverse stress as a potential risk factor in the development of Alzheimer's disease (AD) and data also suggest that normal, physiological stress responses may be impaired in AD. It is possible that pathology associated with AD causes aberrant responses to chronic stress, due to potential alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Recent work in rodent models of AD suggests that chronic adverse stress exacerbates the cognitive def...

  11. Calmodulin Binding Proteins and Alzheimer's Disease.

    Science.gov (United States)

    O'Day, Danton H; Eshak, Kristeen; Myre, Michael A

    2015-01-01

    The small, calcium-sensor protein, calmodulin, is ubiquitously expressed and central to cell function in all cell types. Here the literature linking calmodulin to Alzheimer's disease is reviewed. Several experimentally-verified calmodulin-binding proteins are involved in the formation of amyloid-β plaques including amyloid-β protein precursor, β-secretase, presenilin-1, and ADAM10. Many others possess potential calmodulin-binding domains that remain to be verified. Three calmodulin binding proteins are associated with the formation of neurofibrillary tangles: two kinases (CaMKII, CDK5) and one protein phosphatase (PP2B or calcineurin). Many of the genes recently identified by genome wide association studies and other studies encode proteins that contain putative calmodulin-binding domains but only a couple (e.g., APOE, BIN1) have been experimentally confirmed as calmodulin binding proteins. At least two receptors involved in calcium metabolism and linked to Alzheimer's disease (mAchR; NMDAR) have also been identified as calmodulin-binding proteins. In addition to this, many proteins that are involved in other cellular events intimately associated with Alzheimer's disease including calcium channel function, cholesterol metabolism, neuroinflammation, endocytosis, cell cycle events, and apoptosis have been tentatively or experimentally verified as calmodulin binding proteins. The use of calmodulin as a potential biomarker and as a therapeutic target is discussed. PMID:25812852

  12. Association of Alzheimer's disease and Chlamydophila pneumoniae.

    Science.gov (United States)

    Stallings, Tiffany L

    2008-06-01

    This paper critically reviews the association of infection by Chlamydophila pneumoniae (C. pneumoniae) and Alzheimer's disease (AD). The aging population has increased interest in finding the cause of AD, but studies have yielded contradictory results that are likely due to varying diagnostic tools and different uses of diagnostic tests. Knowledge of AD's characteristics, risk factors, and hypothesized etiologies has expanded since Alois Alzheimer's initial description of AD. Epidemiologic and projection studies provide incidence estimates of AD through a two-stage method: (1) primary diagnosis of dementia by cognitive testing such as Mini-Mental State Examination (MMSE), and (2) clinical diagnosis of AD through criteria such as National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Cross-sectional studies yield prevalence estimates of infection by C. pneumoniae by detecting immunoglobulins through laboratory tests such as microimmunofluorescence (MIF). Studies examining the association of C. pneumoniae and AD are limited, but brain autopsy provides information about presence, proximity to areas associated with AD, and bacterial load. Standardization of diagnostic techniques would allow for better comparability of studies, but uncertainty about the best method of diagnosis of infection by C. pneumoniae and AD may call for revised or novel diagnostic tools.

  13. Predicting cognitive decline in Alzheimer's disease: an integrated analysis

    DEFF Research Database (Denmark)

    Lopez, Oscar L; Schwam, Elias; Cummings, Jeffrey;

    2010-01-01

    Numerous patient- and disease-related factors increase the risk of rapid cognitive decline in patients with Alzheimer's disease (AD). The ability of pharmacological treatment to attenuate this risk remains undefined.......Numerous patient- and disease-related factors increase the risk of rapid cognitive decline in patients with Alzheimer's disease (AD). The ability of pharmacological treatment to attenuate this risk remains undefined....

  14. Dementia: Depression and Alzheimer's Disease

    Science.gov (United States)

    MENU Return to Web version Dementia | Depression and Alzheimer’s Disease What is depression? When doctors talk about depression, they mean the medical illness called major depression. Someone who has ...

  15. Pattern of extrapyramidal signs in Alzheimer's disease.

    Science.gov (United States)

    Tosto, Giuseppe; Monsell, Sarah E; Hawes, Stephen E; Mayeux, Richard

    2015-11-01

    Patients with Alzheimer's disease (AD) often develop extrapyramidal signs (EPS), which increase in frequency as the disease progresses. We aimed to investigate the patterns of presentation of EPS in AD and their correlation with clinical and neuropathological features. 4284 subjects diagnosed with AD from the National Alzheimer's Coordinating Center (NACC) database with at least one abnormal Unified Parkinson's Disease Rating Scale (UPDRS) assessment were included. Individuals were assigned to a discovery sample and a sensitivity analysis sample (moderate and mild dementia, respectively) and a subset of subjects provided neuropathological data (n = 284). Individuals from the Washington Heights and Inwood Columbia Aging Project (WHICAP) served as validation sample. Patterns of presentation of EPS were identified employing categorical principal component analysis (CATPCA). Six principal components were identified in both mild and moderate AD samples: (I) hand movements, alternating movements, finger tapping, leg agility ("limbs bradykinesia"); (II) posture, postural instability, arising from chair, gait and body bradykinesia/hypokinesia ("axial"); (III) limb rigidity ("rigidity"); (IV) postural tremor; (V) resting tremor; (VI) speech and facial expression. Similar results were obtained in the WHICAP cohort. Individuals with hallucinations, apathy, aberrant night behaviors and more severe dementia showed higher axial and limb bradykinesia scores. "Limb bradykinesia" component was associated with a neuropathological diagnosis of Lewy body disease and "axial" component with reduced AD-type pathology. Patterns of EPS in AD show distinct clinical and neuropathological correlates; they share a pattern of presentation similar to that seen in Parkinson's disease, suggesting common pathogenic mechanisms across neurodegenerative diseases. PMID:26338814

  16. Dietary intake of antioxidants and risk of Alzheimer disease

    OpenAIRE

    Engelhart, Marianne; Geerlings, Miriam; Ruitenberg, Annemieke; van Swieten, J C; Witteman, Jacqueline; Breteler, Monique; Hofman, Albert

    2002-01-01

    textabstractCONTEXT: Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress. OBJECTIVE: To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease. DESIGN AND SETTING: The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherland...

  17. Short-term memory binding deficits in Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Abrahams, Sharon; Fabi, Katia; Logie, Robert; Luzzi, Simona; Della Sala, Sergio

    2009-04-01

    Alzheimer's disease impairs long term memories for related events (e.g. faces with names) more than for single events (e.g. list of faces or names). Whether or not this associative or 'binding' deficit is also found in short-term memory has not yet been explored. In two experiments we investigated binding deficits in verbal short-term memory in Alzheimer's disease. Experiment 1: 23 patients with Alzheimer's disease and 23 age and education matched healthy elderly were recruited. Participants studied visual arrays of objects (six for healthy elderly and four for Alzheimer's disease patients), colours (six for healthy elderly and four for Alzheimer's disease patients), unbound objects and colours (three for healthy elderly and two for Alzheimer's disease patients in each of the two categories), or objects bound with colours (three for healthy elderly and two for Alzheimer's disease patients). They were then asked to recall the items verbally. The memory of patients with Alzheimer's disease for objects bound with colours was significantly worse than for single or unbound features whereas healthy elderly's memory for bound and unbound features did not differ. Experiment 2: 21 Alzheimer's disease patients and 20 matched healthy elderly were recruited. Memory load was increased for the healthy elderly group to eight items in the conditions assessing memory for single or unbound features and to four items in the condition assessing memory for the binding of these features. For Alzheimer's disease patients the task remained the same. This manipulation permitted the performance to be equated across groups in the conditions assessing memory for single or unbound features. The impairment in Alzheimer's disease patients in recalling bound objects reported in Experiment 1 was replicated. The binding cost was greater than that observed in the healthy elderly group, who did not differ in their performance for bound and unbound features. Alzheimer's disease grossly impairs the

  18. Inhalational Alzheimer's disease: an unrecognized—and treatable—epidemic

    OpenAIRE

    Bredesen, Dale E.

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic...

  19. Dantrolene, a treatment for Alzheimer disease?

    Science.gov (United States)

    Liang, Li; Wei, Huafeng

    2015-01-01

    Alzheimer disease (AD) is a fatal progressive disease and the most common form of dementia without effective treatments. Previous studies support that the disruption of endoplasmic reticulum Ca through overactivation of ryanodine receptors plays an important role in the pathogenesis of AD. Normalization of intracellular Ca homeostasis could be an effective strategy for AD therapies. Dantrolene, an antagonist of ryanodine receptors and an FDA-approved drug for clinical treatment of malignant hyperthermia and muscle spasms, exhibits neuroprotective effects in multiple models of neurodegenerative disorders. Recent preclinical studies consistently support the therapeutic effects of dantrolene in various types of AD animal models and were summarized in the current review. PMID:25551862

  20. GPCR, a rider of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xiaosong LIU; Jian ZHAO

    2011-01-01

    Alzheimer's disease (AD) is the most common type of dementia that affects thinking,learning,memory and behavior of older people.Based on the previous studies,three pathogenic pathways are now commonly accepted as the culprits of this disease namely,amyloid-β pathway,tauopathology and cholinergic dysfunction.This review focuses on the current findings on the regulatory roles of G protein-coupled receptors (GPCRs) in the pathological progression of AD and discusses the potential of the GPCRs as novel therapeutic targets for AD.

  1. A clinical index to predict progression from mild cognitive impairment to dementia due to Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sei J Lee

    Full Text Available BACKGROUND: Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment. OBJECTIVE: To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings. DESIGN AND PARTICIPANTS: 382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, a multi-site, longitudinal, observational study. MAIN PREDICTORS MEASURES: Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales. MAIN OUTCOME MEASURE: Progression to probable Alzheimer's disease. KEY RESULTS: Subjects had a mean (SD age of 75 (7 years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]. The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75. Fourteen percent of subjects with low risk scores (0-2 points, n = 124 converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n = 223 and 91% of those with high risk scores (9-16 points, n = 35. CONCLUSIONS: An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians

  2. Sparse Multi-Response Tensor Regression for Alzheimer's Disease Study With Multivariate Clinical Assessments.

    Science.gov (United States)

    Li, Zhou; Suk, Heung-Il; Shen, Dinggang; Li, Lexin

    2016-08-01

    Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has recently seen serious increase in the number of affected subjects. In the last decade, neuroimaging has been shown to be a useful tool to understand AD and its prodromal stage, amnestic mild cognitive impairment (MCI). The majority of AD/MCI studies have focused on disease diagnosis, by formulating the problem as classification with a binary outcome of AD/MCI or healthy controls. There have recently emerged studies that associate image scans with continuous clinical scores that are expected to contain richer information than a binary outcome. However, very few studies aim at modeling multiple clinical scores simultaneously, even though it is commonly conceived that multivariate outcomes provide correlated and complementary information about the disease pathology. In this article, we propose a sparse multi-response tensor regression method to model multiple outcomes jointly as well as to model multiple voxels of an image jointly. The proposed method is particularly useful to both infer clinical scores and thus disease diagnosis, and to identify brain subregions that are highly relevant to the disease outcomes. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the proposed method enhances the performance and clearly outperforms the competing solutions. PMID:26960221

  3. Diagnosis and biomarkers of predementia in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Gattaz Wagner F

    2010-12-01

    Full Text Available Abstract In view of the growing prevalence of Alzheimer's disease (AD worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.

  4. Genome instability in Alzheimer disease

    DEFF Research Database (Denmark)

    Hou, Yujun; Song, Hyundong; Croteau, Deborah L;

    2016-01-01

    to the development of noninvasive treatment strategies. Further investigations into the molecular mechanisms connecting DNA damage to AD pathology may help to develop novel treatment strategies for this debilitating disease. Here we provide an overview of the role of genome instability and DNA repair deficiency...... in AD pathology and discuss research strategies that include genome instability as a component....

  5. New cardiovascular targets to prevent late onset Alzheimer disease

    NARCIS (Netherlands)

    Claassen, J.A.H.R.

    2015-01-01

    The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs

  6. Alzheimer - resources

    Science.gov (United States)

    Resources - Alzheimer ... The following organizations are good resources for information on Alzheimer disease : Alzheimer's Association -- www.alz.org Alzheimer's Disease Education and Referral Center -- www.nia.nih.gov/alzheimers ...

  7. Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project.

    Science.gov (United States)

    Refolo, Lorenzo M; Snyder, Heather; Liggins, Charlene; Ryan, Laurie; Silverberg, Nina; Petanceska, Suzana; Carrillo, Maria C

    2012-07-01

    Alzheimer's disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer's disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer's disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer's Association developed the Common Alzheimer's Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.

  8. Immunotherapy against amyloid pathology in Alzheimer's disease.

    Science.gov (United States)

    Galimberti, Daniela; Ghezzi, Laura; Scarpini, Elio

    2013-10-15

    The first drugs developed for Alzheimer's disease (AD), anticholinesterase inhibitors (AchEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AchEI are approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine. These treatments are symptomatic, whereas drugs under development are supposed to modify pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are currently termed "disease modifying" drugs. To block the progression of the disease, they have to interfere with pathogenic steps at the basis of clinical symptoms, including the deposition of extracellular amyloid beta (Aβ) plaques and of intracellular neurofibrillary tangles. The most innovative approach is represented by the vaccination and passive immunization against Aβ peptide. In this article, current knowledge about concluded and ongoing clinical trials with both vaccination with different antigens and passive immunization will be reviewed and discussed.

  9. Atherosclerosis, biomarkers of atherosclerosis and Alzheimer's disease.

    Science.gov (United States)

    Fiolaki, Aidonio; Tsamis, Konstantinos I; Milionis, Haralampos J; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2014-01-01

    Alzheimer's disease (AD) is the most prevalent type of dementia, involving progressive deterioration of neuronal networks. Although the pathophysiological mechanism of AD is not fully elucidated, apart from β-amyloid and tau protein, a diverse number of factors such as cardiovascular risk factors, inflammation, and lipids metabolism may play a significant role. Numerous epidemiological and laboratory studies support vascular injury and inflammation, as key pathological processes. The present review is focused on cardiovascular risk factors, lipids, and circulating biomarkers of inflammation, discussing them as independent mechanisms converging to the same final pathogenetic cascade of AD.

  10. Treatment of Alzheimer Disease With CT Scans

    Science.gov (United States)

    Moore, Eugene R.; Hosfeld, Victor D.; Nadolski, David L.

    2016-01-01

    Alzheimer disease (AD) primarily affects older adults. This neurodegenerative disorder is the most common cause of dementia and is a leading source of their morbidity and mortality. Patient care costs in the United States are about 200 billion dollars and will more than double by 2040. This case report describes the remarkable improvement in a patient with advanced AD in hospice who received 5 computed tomography scans of the brain, about 40 mGy each, over a period of 3 months. The mechanism appears to be radiation-induced upregulation of the patient’s adaptive protection systems against AD, which partially restored cognition, memory, speech, movement, and appetite. PMID:27103883

  11. [Prevention of Alzheimer's Disease and Nutrients].

    Science.gov (United States)

    Otsuka, Mieko

    2016-07-01

    The dietary recommendations for the prevention and management of Alzheimer's disease (AD), are the Mediterranean diet and the Japanese-style diet, both of which contain well-balanced nutrients from fish and vegetables. These diets are rich in vitamin E, carotenes, antioxidant flavonoids, vitamin B12, folate, and n-3PUFA. According to recent review supplementation of folate and vitamin E may protect against elderly people's cognitive decline when the serum folate is dairy products; and a lower amount of carbohydrates and refined sugar. PMID:27395465

  12. A voxel-based MRI morphometric study of Alzheimer's disease

    International Nuclear Information System (INIS)

    Objective: To assess the diagnostic value of voxel-based Morphometry (VBM) in studying Alzheimer's disease (AD). Methods: Graymatter density were comprehensive assessed by means of VBM on T1-weighted MRI volume sets in 19 patients with AD and 15 healthy subjects of similar age and gender ratio, 15 healthy adults. The data were collected on Siemens 1.5 T Sonata MRI systems and analyzed by SPM 99 to generate gray matter density map. Results: Relative to healthy controls, significant clusters of reduced gray matter density were found to affect medial temporal lobe ( hippocampus) (P<0.001). For hippocampus, reduced gray matter density were 1529 in the right and 1281 in the left with right-sided predominance. Moreover, atrophy of right caudate head and left medial thalamus were showed. We demonstrate global asymmetrical cortical atrophy with sparing of the sensorimotor cortex, occipital lobe and cerebellum. Conclusion: The results from VBM are in perfect agreement with those of earlier neuroimaging, which confirmed its value in demonstrating neuroanatomy of AD. VBM, the simple and automatic approach providing a full-brain assessment of AD morphology, has a good clinical perspective. (authors)

  13. Plasma biomarkers of brain atrophy in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Madhav Thambisetty

    Full Text Available Peripheral biomarkers of Alzheimer's disease (AD reflecting early neuropathological change are critical to the development of treatments for this condition. The most widely used indicator of AD pathology in life at present is neuroimaging evidence of brain atrophy. We therefore performed a proteomic analysis of plasma to derive biomarkers associated with brain atrophy in AD. Using gel based proteomics we previously identified seven plasma proteins that were significantly associated with hippocampal volume in a combined cohort of subjects with AD (N = 27 and MCI (N = 17. In the current report, we validated this finding in a large independent cohort of AD (N = 79, MCI (N = 88 and control (N = 95 subjects using alternative complementary methods-quantitative immunoassays for protein concentrations and estimation of pathology by whole brain volume. We confirmed that plasma concentrations of five proteins, together with age and sex, explained more than 35% of variance in whole brain volume in AD patients. These proteins are complement components C3 and C3a, complement factor-I, γ-fibrinogen and alpha-1-microglobulin. Our findings suggest that these plasma proteins are strong predictors of in vivo AD pathology. Moreover, these proteins are involved in complement activation and coagulation, providing further evidence for an intrinsic role of these pathways in AD pathogenesis.

  14. Metal ions, Alzheimer's disease and chelation therapy.

    Science.gov (United States)

    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

  15. Metal ions, Alzheimer's disease and chelation therapy.

    Science.gov (United States)

    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases. PMID:21406339

  16. HEAD TRAUMA AND THE RISK OF ALZHEIMERS-DISEASE

    NARCIS (Netherlands)

    VANDUIJN, CM; TANJA, TA; HAAXMA, R; SCHULTE, W; SAAN, RJ; LAMERIS, AJ; ANTONIDESHENDRIKS, G; HOFMAN, A

    1992-01-01

    A population-based case-control study of the association between head trauma and Alzheimer's disease was conducted in the Netherlands from 1980 to 1987. The study comprised 198 patients with clinically diagnosed early onset Alzheimer's disease and 198 age- and sex-matched population controls. Adjust

  17. Providing Counseling for Individuals with Alzheimer's Disease and Their Caregivers

    Science.gov (United States)

    Granello, Paul F.; Fleming, Matthew S.

    2008-01-01

    Alzheimer's disease is a progressive condition that results in brain wasting and eventual death. With its increasing diagnosis rate, counselors will likely acquire clients with Alzheimer's disease or their caregivers. Important background information and several practical counseling methods are provided that may assist counselors working with this…

  18. Aging and Alzheimer's Disease: Lessons from the Nun Study.

    Science.gov (United States)

    Snowdon, David A.

    1997-01-01

    Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)

  19. Telomere shortening reduces Alzheimer's disease amyloid pathology in mice

    NARCIS (Netherlands)

    Rolyan, Harshvardhan; Scheffold, Annika; Heinrich, Annette; Begus-Nahrmann, Yvonne; Langkopf, Britta Heike; Hoelter, Sabine M.; Vogt-Weisenhorn, Daniela M.; Liss, Birgit; Wurst, Wolfgang; Lie, Dieter Chichung; Thal, Dietmar Rudolf; Biber, Knut; Rudolph, Karl Lenhard

    2011-01-01

    Alzheimer's disease is a neurodegenerative disorder of the elderly and advancing age is the major risk factor for Alzheimer's disease development. Telomere shortening represents one of the molecular causes of ageing that limits the proliferative capacity of cells, including neural stem cells. Studie

  20. Are Judgments of Semantic Relatedness Systematically Impaired in Alzheimer's Disease?

    Science.gov (United States)

    Hornberger, M.; Bell, B.; Graham, K. S.; Rogers, T. T.

    2009-01-01

    We employed a triadic comparison task in patients with Alzheimer's disease (AD) and healthy controls to contrast (a) multidimensional scaling (MDS) and accuracy-based assessments of semantic memory, and (b) degraded-store versus degraded-access accounts of semantic impairment in Alzheimer's disease (AD). Similar to other studies using triadic…

  1. Distinct Mechanisms of Impairment in Cognitive Ageing and Alzheimer's Disease

    Science.gov (United States)

    Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.

    2008-01-01

    Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…

  2. Head trauma and the risk of Alzheimer's disease

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); T.A. Tanja (Teun); R. Haaxma (Rob); W. Schulte (Wim); R.J. Saan; A.J. Lameris; G. Antonides-Hendriks (Gea); A. Hofman (Albert)

    1992-01-01

    textabstractA population-based case-control study of the association between head trauma and Alzheimer's disease was conducted in the Netherlands from 1980 to 1987. The study comprised 198 patients with clinically diagnosed early onset Alzheimer's disease and 198 age- and sex-matched population cont

  3. Software tool for improved prediction of Alzheimer's disease

    DEFF Research Database (Denmark)

    Soininen, Hilkka; Mattila, Jussi; Koikkalainen, Juha;

    2012-01-01

    Diagnostic criteria of Alzheimer's disease (AD) emphasize the integration of clinical data and biomarkers. In practice, collection and analysis of patient data vary greatly across different countries and clinics.......Diagnostic criteria of Alzheimer's disease (AD) emphasize the integration of clinical data and biomarkers. In practice, collection and analysis of patient data vary greatly across different countries and clinics....

  4. The Alzheimer's Disease Knowledge Scale: Development and Psychometric Properties

    Science.gov (United States)

    Carpenter, Brian D.; Balsis, Steve; Otilingam, Poorni G.; Hanson, Priya K.; Gatz, Margaret

    2009-01-01

    Purpose: This study provides preliminary evidence for the acceptability, reliability, and validity of the new Alzheimer's Disease Knowledge Scale (ADKS), a content and psychometric update to the Alzheimer's Disease Knowledge Test. Design and Methods: Traditional scale development methods were used to generate items and evaluate their psychometric…

  5. Longitudinal morphometric MRI study of Alzheimer's disease

    International Nuclear Information System (INIS)

    A longitudinal morphometric MRI study of Alzheimer's disease (AD) was conducted to determine the relationship between the progression of the symptoms and the progression of the brain atrophy. The Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD), developed by Matsuda et al. was used as a method of morphometry to perform the statistical MR image analysis. Thirty-eight patients of AD patients were investigated with VSRAD. These patients were divided into two groups according to the progression of symptoms based on a clinical evaluation. One group was the progress group (20 patients), while the other group was the stable group (18 patients) for comparison. The relationship was investigated between the speed of the symptomatic progression and the change in each VSRAD indicator. Consequently, the entorhinal Z-score and the entorhinal atrophy rate showed a correlation with the speed of the symptomatic progression. The increase of the entorhinal Z-score in the follow-up was larger in the progress group than that in the stable group (0.65/1.28 years in the progress group and 0.05/1.26 years in the stable group.). These results suggest that a rapid symptomatic progression in an AD patient accompanies the rapid progression of atrophy in the entorhinal cortex. (author)

  6. Neuroimaging and Genetic Risk for Alzheimer’s Disease and Addiction-Related Degenerative Brain Disorders

    OpenAIRE

    Roussotte, Florence F.; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D.; Thompson, Paul M.

    2014-01-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer’s disease (AD). Here we describe how multimodal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative ...

  7. Chemokines in CSF of Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2011-06-01

    Full Text Available Some studies have linked the presence of chemokines to the early stages of Alzheimer's disease (AD. Then, the identification of these mediators may contribute to diagnosis. Our objective was to evaluate the levels of beta-amyloid (BA, tau, phospho-tau (p-tau and chemokines (CCL2, CXCL8 and CXCL10 in the cerebrospinal fluid (CSF of patients with AD and healthy controls. The correlation of these markers with clinical parameters was also evaluated. The levels of p-tau were higher in AD compared to controls, while the tau/p-tau ratio was decreased. The expression of CCL2 was increased in AD. A positive correlation was observed between BA levels and all chemokines studied, and between CCL2 and p-tau levels. Our results suggest that levels of CCL2 in CSF are involved in the pathogenesis of AD and it may be an additional useful biomarker for monitoring disease progression.

  8. Canonical feature selection for joint regression and multi-class identification in Alzheimer's disease diagnosis.

    Science.gov (United States)

    Zhu, Xiaofeng; Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2016-09-01

    Fusing information from different imaging modalities is crucial for more accurate identification of the brain state because imaging data of different modalities can provide complementary perspectives on the complex nature of brain disorders. However, most existing fusion methods often extract features independently from each modality, and then simply concatenate them into a long vector for classification, without appropriate consideration of the correlation among modalities. In this paper, we propose a novel method to transform the original features from different modalities to a common space, where the transformed features become comparable and easy to find their relation, by canonical correlation analysis. We then perform the sparse multi-task learning for discriminative feature selection by using the canonical features as regressors and penalizing a loss function with a canonical regularizer. In our experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we use Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images to jointly predict clinical scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) and also identify multi-class disease status for Alzheimer's disease diagnosis. The experimental results showed that the proposed canonical feature selection method helped enhance the performance of both clinical score prediction and disease status identification, outperforming the state-of-the-art methods. PMID:26254746

  9. Alzheimer's disease: Cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies

    NARCIS (Netherlands)

    M.W. Marlatt; P.J. Lucassen; G. Perry; M.A. Smith; X. Zhu

    2008-01-01

    Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and pat

  10. Cerebral microvascular pathology in aging and Alzheimer's disease

    NARCIS (Netherlands)

    Farkas, E; Luiten, PGM

    2001-01-01

    The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to compromised cognitive status. Although the diverse trigger

  11. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... of the next neuron. This cellular circuitry enables communication within the brain. Healthy neurotransmission is important for ... diseases, genetics, and lifestyle factors have on the risk of developing Alzheimer's disease as the brain and ...

  12. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... important for the brain to function well. Alzheimer's disease disrupts this intricate interplay. By compromising the ability of neurons to communicate with one another, the disease over time destroys memory and thinking skills. Scientific ...

  13. FDA Facilitates Research on Earlier Stages of Alzheimer's Disease

    Science.gov (United States)

    ... Updates FDA Facilitates Research on Earlier Stages of Alzheimer's Disease Share Tweet Linkedin Pin it More sharing ... disease.” back to top New Paths for New Alzheimer’s Drugs FDA’s draft guidance aims to encourage research ...

  14. Biological and genetic markers of sporadic Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Engelborghs S

    2001-04-01

    Full Text Available With the development of new treatments, there is an increasing need for early diagnosis of sporadic Alzheimer's disease. Therefore, biological markers allowing positive diagnosis early in the course of the disease are highly desirable. Cerebrospinal fluid levels of protein tau were shown to be significantly increased in patients with Alzheimer's disease. Although sensitivity is high, poor specificity limits the diagnostic value of this marker. The same is true for the 42 amino acid isoform of beta-amyloid protein that is significantly decreased in cerebrospinal fluid of Alzheimer's disease patients. However, combining both markers could improve specificity at least allowing differentiation between Alzheimer's disease, normal ageing and depressive pseudodementia. Other biological markers such as cerebrospinal fluid levels of neurotransmitters, cytokines or superoxide dismutase were shown to have even less diagnostic value. The apolipoprotein epsilon 4 allele is a risk factor for Alzheimer's disease but not a diagnostic marker as many individuals who inherit epsilon 4 do not develop the disease. Till now, a single diagnostic marker allowing discrimination between Alzheimer's disease and other dementias does not exist. Combined cerebrospinal fluid levels of beta-amyloid protein and tau protein might be used as a marker that helps discriminating Alzheimer's disease from normal ageing and depression.

  15. Association studies on susceptibility genes in Alzheimer disease

    OpenAIRE

    Björk, Behnosh Fakhri

    2008-01-01

    Alzheimer disease (AD) is the most common form of dementia in the elderly. Due to the complexity of AD, it has been difficult to find genetic risk factors predisposing to disease. To date, three genes (APP, PSEN1 and PSEN2) with disease causing genetic variants have been reported for the rare early onset monogenic forms of AD. For the more prevalent, late onset Alzheimer disease (LOAD), the epsilon4 allele of the APOE gene, is the only confirmed genetic risk factor. However,...

  16. Alzheimer disease and pre-emptive suicide.

    Science.gov (United States)

    Davis, Dena S

    2014-08-01

    There is a flood of papers being published on new ways to diagnose Alzheimer disease (AD) before it is symptomatic, involving a combination of invasive tests (eg, spinal tap), and pen and paper tests. This changes the landscape with respect to genetic tests for risk of AD, making rational suicide a much more feasible option. Before the availability of these presymptomatic tests, even someone with a high risk of developing AD could not know if and when the disease was approaching. One could lose years of good life by committing suicide too soon, or risk waiting until it was too late and dementia had already sapped one of the ability to form and carry out a plan. One can now put together what one knows about one's risk, with continuing surveillance via these clinical tests, and have a good strategy for planning one's suicide before one becomes demented. This has implications for how these genetic and clinical tests are marketed and deployed, and the language one uses to speak about them. The phrase 'there is nothing one can do' is insulting and disrespectful of the planned suicide option, as is the language of the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) studies and others that conclude that it is 'safe' to tell subjects their risk status for AD. Further, the argument put forward by some researchers that presymptomatic testing should remain within research protocols, and the results not shared with subjects until such time as treatments become available, disrespects the autonomy of people at high risk who consider suicide an option.

  17. Domain adaptation for Alzheimer's disease diagnostics.

    Science.gov (United States)

    Wachinger, Christian; Reuter, Martin

    2016-10-01

    With the increasing prevalence of Alzheimer's disease, research focuses on the early computer-aided diagnosis of dementia with the goal to understand the disease process, determine risk and preserving factors, and explore preventive therapies. By now, large amounts of data from multi-site studies have been made available for developing, training, and evaluating automated classifiers. Yet, their translation to the clinic remains challenging, in part due to their limited generalizability across different datasets. In this work, we describe a compact classification approach that mitigates overfitting by regularizing the multinomial regression with the mixed ℓ1/ℓ2 norm. We combine volume, thickness, and anatomical shape features from MRI scans to characterize neuroanatomy for the three-class classification of Alzheimer's disease, mild cognitive impairment and healthy controls. We demonstrate high classification accuracy via independent evaluation within the scope of the CADDementia challenge. We, furthermore, demonstrate that variations between source and target datasets can substantially influence classification accuracy. The main contribution of this work addresses this problem by proposing an approach for supervised domain adaptation based on instance weighting. Integration of this method into our classifier allows us to assess different strategies for domain adaptation. Our results demonstrate (i) that training on only the target training set yields better results than the naïve combination (union) of source and target training sets, and (ii) that domain adaptation with instance weighting yields the best classification results, especially if only a small training component of the target dataset is available. These insights imply that successful deployment of systems for computer-aided diagnostics to the clinic depends not only on accurate classifiers that avoid overfitting, but also on a dedicated domain adaptation strategy. PMID:27262241

  18. Vaccination against Alzheimer disease: an update on future strategies.

    Science.gov (United States)

    Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

    2014-01-01

    Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer.

  19. Interneurons in the human olfactory system in Alzheimer's disease.

    Science.gov (United States)

    Saiz-Sanchez, Daniel; Flores-Cuadrado, Alicia; Ubeda-Bañon, Isabel; de la Rosa-Prieto, Carlos; Martinez-Marcos, Alino

    2016-02-01

    The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.

  20. The rat as an animal model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind...... that of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat...... as an animal model of Alzheimer's disease....

  1. Volume changes in Alzheimer's disease and mild cognitive impairment: cognitive associations

    International Nuclear Information System (INIS)

    To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. (orig.)

  2. An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Daniel Schmitter

    2015-01-01

    Full Text Available Voxel-based morphometry from conventional T1-weighted images has proved effective to quantify Alzheimer's disease (AD related brain atrophy and to enable fairly accurate automated classification of AD patients, mild cognitive impaired patients (MCI and elderly controls. Little is known, however, about the classification power of volume-based morphometry, where features of interest consist of a few brain structure volumes (e.g. hippocampi, lobes, ventricles as opposed to hundreds of thousands of voxel-wise gray matter concentrations. In this work, we experimentally evaluate two distinct volume-based morphometry algorithms (FreeSurfer and an in-house algorithm called MorphoBox for automatic disease classification on a standardized data set from the Alzheimer's Disease Neuroimaging Initiative. Results indicate that both algorithms achieve classification accuracy comparable to the conventional whole-brain voxel-based morphometry pipeline using SPM for AD vs elderly controls and MCI vs controls, and higher accuracy for classification of AD vs MCI and early vs late AD converters, thereby demonstrating the potential of volume-based morphometry to assist diagnosis of mild cognitive impairment and Alzheimer's disease.

  3. Volume changes in Alzheimer's disease and mild cognitive impairment: cognitive associations

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Matthew C.; Barnes, Josephine; Nielsen, Casper; Clegg, Shona L.; Blair, Melanie; Douiri, Abdel; Boyes, Richard G.; Fox, Nick C. [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); Kim, Lois G. [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); London School of Hygiene and Tropical Medicine, London (United Kingdom); Leung, Kelvin K.; Ourselin, Sebastien [UCL Institute of Neurology, Dementia Research Centre, London (United Kingdom); University College London, Centre for Medical Image Computing, London (United Kingdom)

    2010-03-15

    To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. (orig.)

  4. Fish, docosahexaenoic acid and Alzheimer's disease. : Fish, Docosahexaenoic Acid and Alzheimer's Disease

    OpenAIRE

    Cunnane, Stephen,; Plourde, Mélanie; Pifferi, Fabien; Bégin, Michel; Féart, Catherine; Barberger-Gateau, Pascale

    2009-01-01

    International audience; Cognitive decline in the elderly, particularly Alzheimer's disease (AD), is a major socio-economic and healthcare concern. We review here the literature on one specific aspect of diet affecting AD, that of the omega3 fatty acids, particularly the brain's principle omega3 fatty acid - docosahexaenoic acid (DHA). DHA has deservedly received wide attention as a nutrient supporting both optimal brain development and for cardiovascular health. Our aim here is to critically ...

  5. Metal dyshomeostasis and oxidative stress in Alzheimer's disease.

    Science.gov (United States)

    Greenough, Mark A; Camakaris, James; Bush, Ashley I

    2013-04-01

    Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics.

  6. Nutrition and the risk of Alzheimer's disease.

    Science.gov (United States)

    Hu, Nan; Yu, Jin-Tai; Tan, Lin; Wang, Ying-Li; Sun, Lei; Tan, Lan

    2013-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD. PMID:23865055

  7. Mitochondria, cognitive impairment, and Alzheimer's disease.

    Science.gov (United States)

    Mancuso, M; Calsolaro, V; Orsucci, D; Carlesi, C; Choub, A; Piazza, S; Siciliano, G

    2009-01-01

    To date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic, and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress, and accumulation of Abeta, which in a vicious cycle reinforce the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria, and especially of the mtDNA, in the cascade of events leading to neurodegeneration, dementia, and AD. PMID:20798880

  8. Nutrition and the Risk of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Nan Hu

    2013-01-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.

  9. Memory for music in Alzheimer's disease: unforgettable?

    Science.gov (United States)

    Baird, Amee; Samson, Séverine

    2009-03-01

    The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD. PMID:19214750

  10. Disruption of zinc homeostasis in Alzheimer's disease

    Science.gov (United States)

    Robertson, J. D.; Crafford, A. M.; Markesbery, W. R.; Lovell, M. A.

    2002-04-01

    The basic hypothesis being tested is that, in Alzheimer's disease (AD), the delicate balance of brain Zn is disrupted and may play a role in the pathogenesis of neuron degeneration. Micro-PIXE measurements reveal a significant elevation of Zn in senile plaques (SP) in AD brain compared with adjacent neuropil and a significant increase in AD neuropil compared to control neuropil. The observation of elevated Zn in SP is of interest because the amyloid precursor protein contains a Zn binding site that may prevent normal cleavage leading to the generation of a toxic fragment of beta amyloid, the constituent of SP. The potential of using laser-ablation inductively coupled plasma mass spectrometry as a complimentary microprobe technique is also presented.

  11. Alzheimer's disease and other dementias in Canada.

    Science.gov (United States)

    Wong, Suzy L; Gilmour, Heather; Ramage-Morin, Pamela L

    2016-05-18

    This article provides information on Alzheimer's disease and other dementias, using the 2010/2011 Canadian Community Health Survey, the 2011/2012 Survey of Neurological Conditions in Institutions in Canada, and the 2011 Survey on Living with Neurological Conditions in Canada. Among Canadians aged 45 or older, an estimated 0.8% in private households and 45% in long-term residential care facilities had a diagnosis of dementia. Prevalence rose with age. The vast majority of people with dementia in private households received assistance with medical care (81%), housework and home maintenance (83%), meal preparation (88%), emotional support (90%), transportation (92%), and managing care (92%). Among those receiving assistance, 85% relied, at least in part, on family, friends or neighbours. The primary caregiver tended to be a spouse (46%) or an adult child (44%), most of whom were daughters (71%). The majority of primary caregivers lived in the same household (83%) and provided daily care (86%). PMID:27192206

  12. PET and SPECT investigations in Alzheimer's disease

    International Nuclear Information System (INIS)

    Nuclear medicine offers a wide range of possibilities to investigate dementia. Various SPECT and PET tracers will be introduced in this article first. Different questions concerning evaluation of dementia are discussed taking Alzheimer's disease (AD) as an example. It is important to perform nuclear medicine investigations on high technical level, using standardized methods as statistical parametric mapping (SPM) for evaluation. If neuroprotective therapies are available, an early diagnosis, the determination of risk factors and longitudinal investigations will be the focus of interest and the main goal of nuclear medicine. Apart from measuring cerebral perfusion and glucose metabolism the development of new ligands, concerning the cholinergic system and the visualization of amyloid plaques, is of great importance. (orig.)

  13. Disruption of zinc homeostasis in Alzheimer's disease

    International Nuclear Information System (INIS)

    The basic hypothesis being tested is that, in Alzheimer's disease (AD), the delicate balance of brain Zn is disrupted and may play a role in the pathogenesis of neuron degeneration. Micro-PIXE measurements reveal a significant elevation of Zn in senile plaques (SP) in AD brain compared with adjacent neuropil and a significant increase in AD neuropil compared to control neuropil. The observation of elevated Zn in SP is of interest because the amyloid precursor protein contains a Zn binding site that may prevent normal cleavage leading to the generation of a toxic fragment of beta amyloid, the constituent of SP. The potential of using laser-ablation inductively coupled plasma mass spectrometry as a complimentary microprobe technique is also presented

  14. Metaphor comprehension in Alzheimer's disease: novelty matters.

    Science.gov (United States)

    Amanzio, Martina; Geminiani, Giuliano; Leotta, Daniela; Cappa, Stefano

    2008-10-01

    The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of non-conventional (novel) metaphor comprehension. This ability was not related to global cognitive deterioration or to deficits in the cognitive domains of attention, memory and language comprehension. On the other hand, the impairment in verbal reasoning appeared to be relevant for both novel and conventional metaphor comprehension. The relationship between novel metaphor comprehension and performance in the visual-spatial planning task of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) suggests that executive impairment, possibly related to prefrontal dysfunction, may be responsible for the pAD patients' poor performance in novel metaphor comprehension. The present findings suggest a role of the prefrontal cortex in novel metaphor comprehension.

  15. Immunotherapeutic Strategies for Alzheimer's Disease Treatment

    Directory of Open Access Journals (Sweden)

    Beka Solomon

    2009-01-01

    Full Text Available Naturally occurring antibodies against amyloid-β peptides have been found in human cerebrospinal fluid and in the plasma of healthy individuals, but were significantly lower in Alzheimer's disease (AD patients, suggesting that AD may be an immunodeficient disorder. The performance of anti-amyloid-β antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system, preventing and dissolving amyloid-β plaques. Moreover, these antibodies protected the mice from learning and age-related memory deficits. Active and/or passive immunization against the amyloid-β peptide has been proposed as a method for preventing and/or treating AD. Immunotherapy represents fascinating ways to test the amyloid hypothesis and offers genuine opportunities for AD treatment, but requires careful antigen and antibody selection to maximize efficacy and minimize adverse events.

  16. Memory for music in Alzheimer's disease: unforgettable?

    Science.gov (United States)

    Baird, Amee; Samson, Séverine

    2009-03-01

    The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD.

  17. Molecular and cellular pathophysiology of preclinical Alzheimer's disease.

    Science.gov (United States)

    Mufson, Elliott J; Ikonomovic, Milos D; Counts, Scott E; Perez, Sylvia E; Malek-Ahmadi, Michael; Scheff, Stephen W; Ginsberg, Stephen D

    2016-09-15

    Although the two pathological hallmarks of Alzheimer's disease (AD), senile plaques composed of amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau, have been studied extensively in postmortem AD and relevant animal and cellular models, the pathogenesis of AD remains unknown, particularly in the early stages of the disease where therapies presumably would be most effective. We and others have demonstrated that Aβ plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia. In this regard, aged people with no cognitive impairment (NCI), mild cognitive impairment (MCI, a presumed prodromal AD transitional state, and AD all present at autopsy with varying levels of pathological hallmarks. Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Aβ plaques. However, correlations are even higher between cognitive decline and synaptic loss. In this review, we illustrate relevant clinical pathological research in preclinical AD and throughout the progression of dementia in several areas including Aβ and tau pathobiology, single population expression profiling of vulnerable hippocampal and basal forebrain neurons, neuroplasticity, neuroimaging, cerebrospinal fluid (CSF) biomarker studies and their correlation with antemortem cognitive endpoints. In each of these areas, we provide evidence for the importance of studying the pathological hallmarks of AD not in isolation, but rather in conjunction with other molecular, cellular, and imaging markers to provide a more systematic and comprehensive assessment of the multiple changes that occur during the transition from NCI to MCI to frank AD. PMID:27185734

  18. Understanding Family Interaction Patterns in Families With Alzheimer's Disease.

    Science.gov (United States)

    Schaber, Patricia; Blair, Kate; Jost, Ellen; Schaffer, Molly; Thurner, Emily

    2016-01-01

    This qualitative study explores the dynamic changes that occur in family interaction patterns when Alzheimer's disease is present. Semi-structured interviews were conducted with 15 participants who have a family member with the disease. Using modified analytic induction, guided by the dimensions of the Family Fundamental Interpersonal Relations Orientation (FIRO) Model, participants shared how Alzheimer's disease affected family structure, control dynamics, and intimacy among family members. Findings demonstrate that (a) families reorganize and restructure based on geographic proximity and shifting roles, act out of filial responsibility, and strive to preserve shared meanings and rituals; (b) decision making increases around care of the person with Alzheimer's disease and shifts to the primary caregiver or other family members based on their abilities; and (c) expressions of intimacy intensify while personality is preserved in the person with the disease. The Family FIRO model can inform practitioners using family-centered care with families with Alzheimer's disease.

  19. Explorative and targeted neuroproteomics in Alzheimer's disease.

    Science.gov (United States)

    Brinkmalm, Ann; Portelius, Erik; Öhrfelt, Annika; Brinkmalm, Gunnar; Andreasson, Ulf; Gobom, Johan; Blennow, Kaj; Zetterberg, Henrik

    2015-07-01

    Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other higher brain functions. Neuropathologically, the disease is characterized by accumulation of a 42 amino acid peptide called amyloid β (Aβ42) in extracellular senile plaques, intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Biomarker assays capturing these pathologies have been developed for use on cerebrospinal fluid samples but there are additional molecular pathways that most likely contribute to the neurodegeneration and full clinical expression of AD. One way of learning more about AD pathogenesis is to identify novel biomarkers for these pathways and examine them in longitudinal studies of patients in different stages of the disease. Here, we discuss targeted proteomic approaches to study AD and AD-related pathologies in closer detail and explorative approaches to discover novel pathways that may contribute to the disease. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.

  20. Assessing impulsivity changes in Alzheimer disease.

    Science.gov (United States)

    Rochat, Lucien; Delbeuck, Xavier; Billieux, Joël; d'Acremont, Mathieu; Van der Linden, Anne-Claude Juillerat; Van der Linden, Martial

    2008-01-01

    Impulsive behaviors are common in brain-damaged patients including those with neurodegenerative diseases such as Alzheimer disease (AD). The objective of this study was to develop and validate a short version of the UPPS Impulsive Behavior Scale assessing changes on 4 different dimensions of impulsivity, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking, arising in the course of a neurodegenerative disease. To this end, caregivers of 83 probable AD patients completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale. Exploratory and confirmatory factor analyses of the data were performed and revealed that a model with 4 distinct but related latent variables corresponding to 4 different dimensions of impulsivity fit the data best. Furthermore, the results showed that lack of perseverance, followed by lack of premeditation and urgency, increased after the onset of the disease, whereas sensation seeking decreased. Overall, the multifaceted nature of impulsivity was confirmed in a sample of AD patients, whose caregivers reported significant changes regarding each facet of impulsivity. Consequently, the short version of the UPPS Impulsive Behavior Scale opens up interesting prospects for a better comprehension of behavioral symptoms of dementia. PMID:18580596

  1. Biomaterials for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Hadavi, Darya; Poot, André A

    2016-01-01

    Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood-brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies. PMID:27379232

  2. Perception of Alzheimer Disease in Iranian Traditional Medicine

    Science.gov (United States)

    Saifadini, Rostam; Tajadini, Haleh; Choopani, Rasool; Mehrabani, Mitra; Kamalinegad, Mohamad; Haghdoost, Aliakbar

    2016-01-01

    Context: Alzheimer disease (AD) is the most common cause of dementia. In regards to the world’s aging population, control and treatment of AD will be one of the major concerns of global public health in the next century. Alzheimer disease was not mentioned with the same phrase or its equivalent in traditional medical texts. The main of present paper was to investigate symptoms and causes of alzheimer disease from the view point of Iranian traditional medicine. Evidence Acquisition: In this qualitative study, we searched reliable sources of Iranian traditional medicine such as Canon of Medicide by Avicenna (Al-Quanon fi- tibb), Aghili cure by Aghili’s (Molajat-E-aghili), Tib-E-Akbari, Exire -E-Aazam and Sharh-E-Asbab and some reliable resources of neurology were probed base on keywords to find a disease that had the most overlap in terms of symptoms with alzheimer disease. By taking from the relevant materials, the extracted texts were compared and analyzed. Results: Findings showed that alzheimer disease has the most overlap with Nesyan (fisad-e-zekr, fisad-e-fekr and fisad-e-takhayol) symptoms in Iranian traditional medicine. Although this is not a perfect overlap and there are causes, including coldness and dryness of the brain or coldness and wetness that could also lead to alzheimer disease according to Iranian traditional medicine. Conclusions: According to Iranian traditional medicine, The brain dystemperement is considered the main causes of alzheimer disease. By correcting the brain dystemperement, alzheimer can be well managed. This study helps to suggest a better strategy for preventing and treating alzheimer in the future. PMID:27247784

  3. Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes.

    Science.gov (United States)

    Hohman, Timothy J; Samuels, Lauren R; Liu, Dandan; Gifford, Katherine A; Mukherjee, Shubhabrata; Benson, Elleena M; Abel, Ty; Ruberg, Frederick L; Jefferson, Angela L

    2015-09-01

    Alzheimer's disease (AD) biomarkers and stroke risk factors independently predict cognitive impairment, likely through independent disease pathways. However, limited work has sought to describe the dynamic interplay between these important risk factors. This article evaluated the interaction between stroke risk and AD biomarkers on hippocampal volume and cognitive performance. We first evaluated the interaction between stroke risk factors and AD biomarkers using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 1202). We then extended our findings to an independent autopsy data set from the National Alzheimer's Coordinating Center (NACC, n = 1122) using measures of AD pathology. Stroke risk was quantified using the Framingham Stroke Risk Profile. In ADNI, stroke risk interacted with tau and amyloid levels in relation to baseline and longitudinal cognitive performance. Similarly, in NACC, stroke risk interacted with amyloid and tau positivity on cognitive performance. The effect of stroke risk factors on cognition was strongest in the absence of AD biomarkers or neuropathology, providing additional evidence that AD biomarkers and stroke risk factors relate to cognition through independent pathways.

  4. Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Florian Amtage

    2014-06-01

    Full Text Available We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease.

  5. Can We Prevent Parkinson's and Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Kedar N

    2003-01-01

    Full Text Available Parkinson's disease (PD and Alzheimer's (AD are major progressive neurological disorders, the risk of which increases with advancing age (65 years and over. In familial cases, however, early onset of disease (about 35 years is observed. In spite of extensive basic and clinical research on PD and AD, no preventive or long-term effective treatment strategies are available. Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of sporadic PD and AD. Even a-synuclein and b-amyloid fragments that are associated with the PD and AD, respectively, mediate part of their action via oxidative stress. Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. This review provides a brief description of the epidemiology and pathogenesis of PD and AD, and the scientific rationale for the use of multiple antioxidants in the prevention of these neurological diseases.

  6. [Angiotensin converting enzyme and Alzheimer's disease].

    Science.gov (United States)

    Kugaevskaia, E V

    2013-01-01

    Alzheimer's disease (AD) is an incurable degenerative disease of the central nervous system, leading to dementia. The basis of AD is neurodegenerative process that leads to death of neurons in the cerebral cortex. This neurodegenerative process is associated with the formation of neurofibrillary tangles in the brain and the deposition of senile plaques, the main component of which is a beta-amyloid peptide (Abeta). Risk factors for AD are age, as well as hypertension, atherosclerosis, diabetes and hypercholesterolemia in the pathogenesis of which involved angiotensin converting enzyme (ACE)--key enzyme of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems. Recently it was discovered that ACE, along with other metallopeptidases, participates in the metabolism of Abeta, cleaving the bonds at the N-terminal and C-terminal region of the molecule Abeta. The role of the ACE in the degradation processes of Abeta takes an interest. It is associated with the fact that the using of ACE inhibitors is the main therapeutic approach used in the treatment of various forms of hypertension and other cardiovascular diseases. However, until now not been resolved, can be used antihypertensive drugs that inhibit RAS for the treatment or prevention of AD. Currently, there are numerous studies on finding the relationship between RAS and AD. PMID:23650720

  7. Neuroinflammation in Alzheimer's disease wanes with age

    Directory of Open Access Journals (Sweden)

    Hoozemans Jeroen JM

    2011-12-01

    Full Text Available Abstract Background Inflammation is a prominent feature in Alzheimer's disease (AD. It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated. Methods In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years. The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1, HLA class II (CR3/43 and glial fibrillary acidic protein (GFAP. Results By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD. Conclusion Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.

  8. Alzheimer's disease drug development: translational neuroscience strategies.

    Science.gov (United States)

    Cummings, Jeffrey L; Banks, Sarah J; Gary, Ronald K; Kinney, Jefferson W; Lombardo, Joseph M; Walsh, Ryan R; Zhong, Kate

    2013-06-01

    Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

  9. Association between Cytokine production and disease severity in Alzheimer's disease.

    OpenAIRE

    Farahzad Jabbari Azad; Ali Talaei; Houshang Rafatpanah; Hadis Yousefzadeh; Rahele Jafari; Andishe Talaei; Reza Farid Hosseini

    2014-01-01

    The role of transforming growth factor (TGF)-β1, interferon (IFN)-γ, interleukin (IL)-2, IL-3, and IL-6 in the pathogenesis of Alzheimer's Disease (AD) has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients' disease risk. 40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and g...

  10. Alzheimer's Project

    Medline Plus

    Full Text Available ... Alzheimer's Gala A Night at Sardi's Alzheimer's Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s ... HBO's "THE ALZHEIMER'S PROJECT" takes a look at the faces behind the disease - and the forces leading us ...

  11. Support for an hypothesis linking Alzheimer`s disease and Down syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Geller, L.N.; Benjamin, M.B.; Dressler, D. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    A connection between Alzheimer`s disease (AD) and Down syndrome (trisomy 21) is indicated by the fact that Down syndrome individuals develop AD neuropathology by the third or fourth decade of life. One explanation for the connection between AD and Down syndrome would be that the overexpression of a gene or genes on chromosome 21 results in Alzheimer`s disease, the most likely candidate being the amyloid precursor protein (APP) gene. However, mutations in the APP gene have been found to be associated with only a very small percentage of familial AD cases. An alternative cause of some Alzheimer`s disease cases may be sporadic trisomy of chromosome 21, resulting from mutations or toxins that cause chromosome nondisjunction. Several predictions can be made based on this hypothesis. One prediction is that there should be more trisomy 21 in cells from AD individuals than from unaffected controls. Using quantitative fluorescence in situ hybridization to compare the number of trisomy chromosome 21 cells in cultured fibroblasts from AD and unaffected individuals, we have shown that there are a significantly larger number of trisomy 21 cells from AD individuals. Another prediction is that a defect in the mitotic spindle apparatus could be the underlying cause of the aneuploidy. Cultured lymphoblasts from AD and unaffected individuals were briefly exposed to the microtubule-disrupting agent colchicine. As assayed by the subsequent appearance of metaphase chromosomes showing centromere separation, cells from AD patients were significantly more sensitive to colchicine treatment compared to cells from unaffected individuals, supporting the prediction of an altered spindle apparatus. Finally, we would predict that both types of patients should share some physical symptoms. We have also found that AD, like Down`s patients, are hypersensitive to the effect of the cholinergic antagonist, tropicamide, on pupil dilation, which may serve as a diagnostic test for Alzheimer`s disease.

  12. Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

  13. Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

    Science.gov (United States)

    Matoug, S.; Abdel-Dayem, A.; Passi, K.; Gross, W.; Alqarni, M.

    2012-02-01

    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

  14. The rationale for deep brain stimulation in Alzheimer's disease.

    Science.gov (United States)

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials. PMID:26443701

  15. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... receive messages from each other as electrical charges travel down the axon to the end of the ... another place. These released fragments are thought to benefit neurons. In Alzheimer's disease, the first cut is ...

  16. Lentivirus-expressed siRNA vectors against Alzheimer disease.

    Science.gov (United States)

    Peng, Kevin A; Masliah, Eliezer

    2010-01-01

    Amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer disease, and the accumulation of APP products ultimately leads to the familiar histopathological and clinical manifestations associated with this most common form of dementia. A protein that has been shown to promote APP accumulation is beta-secretase (beta-site APP cleaving enzyme 1, or BACE1), which is increased in the cerebrospinal fluid in those affected with Alzheimer disease. Through in vivo studies using APP transgenic mice, we demonstrated that decreasing the expression of BACE1 via lentiviral vector delivery of BACE1 siRNA has the potential for significantly reducing the cleavage of APP, accumulation of these products, and consequent neurodegeneration. As such, lentiviral-expressed siRNA against BACE1 is a therapeutic possibility in the treatment of Alzheimer disease. We detail the use of lentivirus-expressed siRNA as a method to ameliorate Alzheimer disease neuropathology in APP transgenic mice.

  17. Could Lipoprotein Lipase Play a Role in Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Jean-Francois Blain

    2004-01-01

    Full Text Available This paper reviews recent literature on the role of lipoprotein lipase in the central nervous system with a focus on its recently described role in synaptic remodeling. This novel role could have implication for Alzheimer's disease treatment.

  18. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... proteins in the neuron's cell membrane are processed differently. Normally, an enzyme called alpha-secretase snips amyloid ... Alzheimer's disease, but there is still much to learn. What other changes are taking place in the ...

  19. Melanopsin retinal ganglion cell loss in Alzheimer's disease

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Koronyo, Yosef;

    2015-01-01

    OBJECTIVE: Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer's disease (AD). We investigated mRGCs in AD, hypothesizing their contribution to circadian dysfunction. METHODS: We assessed retinal nerve...

  20. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available ... over time destroys memory and thinking skills. Scientific research has revealed some of the brain changes that ... disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's ...

  1. Inside the Brain: Unraveling the Mystery of Alzheimer's Disease

    Medline Plus

    Full Text Available The human brain is a remarkable organ. Complex chemical and electrical processes take place within our brains that let ... of developing Alzheimer's disease as the brain and body age? Scientific research is helping to unravel the ...

  2. Relationships between cognitive performance, neuroimaging, and vascular disease: the DHS-Mind Study

    Science.gov (United States)

    Hsu, Fang-Chi; Raffield, Laura M.; Hugenschmidt, Christina E.; Cox, Amanda; Xu, Jianzhao; Carr, J. Jeffery; Freedman, Barry I.; Maldjian, Joseph A.; Williamson, Jeff D.; Bowden, Donald W.

    2015-01-01

    Background Type 2 diabetes mellitus increases risk for cognitive decline and dementia; elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-Mind using a battery of cognitive tests, neuroimaging measures, and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified plaque (CAC). We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. Methods Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes, and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. Results Higher total brain volume (TBV) was associated with better performance on the Digit Symbol Substitution Task (DSST) and Semantic Fluency (both p≤7.0 x 10−4). Higher gray matter volume (GMV) was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p≤9.0 x 10−4). Adjusting for CAC caused minimal changes to the results. Conclusions Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures. PMID:26185004

  3. Research Sheds Light on Mechanism of Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Scientists from the Shanghai Institute of Materia Medica (SIMM) under the CAS Shanghai Institutes for Biological Sciences have made significant progress in suggesting a possible mechanism for the accumulation of amyloid β-peptides (Aβs), which are believed to cause Alzheimer's disease. Aβs are fragments of a protein that is snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would be broken down and eliminated. In Alzheimer's disease, unfortunately, the fragments accumulate to form hard, insoluble plaques, which are the characteristic lesions found in Alzheimer's patients and could dramatically inhibit several genes critical to memory and learning.

  4. Clinical utility of color-form naming in Alzheimer's disease: preliminary evidence

    DEFF Research Database (Denmark)

    Nielsen, Niels Peter; Wiig, Elisabeth H; Warkentin, Siegbert;

    2004-01-01

    Performances on Alzheimer's Quick Test color-form naming and Mini-Mental State Examination were compared for 38 adults with Alzheimer's disease and 38 age- and sex-matched normal controls. Group means differed significantly and indicated longer naming times by adults with Alzheimer's disease...... associated with Alzheimer's disease, are preliminary given the relatively small sample....

  5. Stem cell strategies for Alzheimer's disease therapy.

    Science.gov (United States)

    Sugaya, K; Alvarez, A; Marutle, A; Kwak, Y D; Choumkina, E

    2006-06-01

    We have found much evidence that the brain is capable of regenerating neurons after maturation. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for cell-replacement therapies for neurodegenerative diseases including Alzheimer's disease (AD). However, ethical and practical issues associated with HNSCs compel us to explore alternative strategies. Here, we report novel technologies to differentiate adult human mesenchymal stem cells, a subset of stromal cells in the bone marrow, into neural cells by modifying DNA methylation or over expression of nanog, a homeobox gene expressed in embryonic stem cells. We also report peripheral administrations of a pyrimidine derivative that increases endogenous stem cell proliferation improves cognitive function of the aged animal. Although these results may promise a bright future for clinical applications used towards stem cell strategies in AD therapy, we must acknowledge the complexity of AD. We found that glial differentiation takes place in stem cells transplanted into amyloid-( precursor protein (APP) transgenic mice. We also found that over expression of APP gene or recombinant APP treatment causes glial differentiation of stem cells. Although further detailed mechanistic studies may be required, RNA interference of APP or reduction of APP levels in the brain can significantly reduced glial differentiation of stem cells and may be useful in promoting neurogenesis after stem cell transplantation. PMID:16953146

  6. Computed tomography of the temporal horns at Alzheimer's disease

    International Nuclear Information System (INIS)

    In the literature there are different opinions referring to the involvement of the temporal lobes or horns at Alzheimer's disease. Conventionally computed tomogram of the head does not include the temporal horn in its full length. A simple method to demonstrate the temporal horns after cranial computer tomography is described. It allows the evaluation of temporal lobe and temporal horn if questionable alterations at Alzheimer's disease are to be discussed. (orig.)

  7. Mitochondria Are Related to Synaptic Pathology in Alzheimer's Disease

    OpenAIRE

    Baloyannis, Stavros J.

    2011-01-01

    Morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer's disease, been associated with oxidative stress and A β -peptide-induced toxicity. We proceeded to estimation of mitochondria on electron micrographs of autopsy specimens of Alzheimer's disease. We found substantial morphological and morphometric changes of the mitochondria in the neurons of the hippocampus, the neocortex, the cerebellar cortex, the thalamus, the globus pallidus, the red nuc...

  8. Functional neuroanatomy of auditory scene analysis in Alzheimer's disease

    OpenAIRE

    Golden, Hannah L.; Jennifer L. Agustus; Johanna C. Goll; Downey, Laura E; Mummery, Catherine J.; Jonathan M Schott; Crutch, Sebastian J.; Jason D Warren

    2015-01-01

    Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory ‘foreground’ and ‘back...

  9. Proxy-rated quality of life in Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Bhattacharya, Suvosree; Waldemar, Gunhild;

    2012-01-01

    The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months.......The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months....

  10. Hallucinations, delusions, and cognitive decline in Alzheimer's disease

    OpenAIRE

    Wilson, R.; Gilley, D; Bennett, D.; Beckett, L.; Evans, D.

    2000-01-01

    OBJECTIVES—To examine the occurrence of hallucinations and delusions in Alzheimer's disease over a 4 year period and their association with rate of cognitive decline.
METHODS—A cohort of 410 persons with clinically diagnosed Alzheimer's disease underwent annual clinical evaluations over a 4 year period. Participation in follow up exceeded 90% in survivors. Evaluations included structured informant interview, from which the presence or absence of hallucinations and delusio...

  11. A Structural Parametrization of the Brain Using Hidden Markov Models-Based Paths in Alzheimer's Disease.

    Science.gov (United States)

    Martinez-Murcia, Francisco J; Górriz, Juan M; Ramírez, Javier; Ortiz, Andres

    2016-11-01

    The usage of biomedical imaging in the diagnosis of dementia is increasingly widespread. A number of works explore the possibilities of computational techniques and algorithms in what is called computed aided diagnosis. Our work presents an automatic parametrization of the brain structure by means of a path generation algorithm based on hidden Markov models (HMMs). The path is traced using information of intensity and spatial orientation in each node, adapting to the structure of the brain. Each path is itself a useful way to characterize the distribution of the tissue inside the magnetic resonance imaging (MRI) image by, for example, extracting the intensity levels at each node or generating statistical information of the tissue distribution. Additionally, a further processing consisting of a modification of the grey level co-occurrence matrix (GLCM) can be used to characterize the textural changes that occur throughout the path, yielding more meaningful values that could be associated to Alzheimer's disease (AD), as well as providing a significant feature reduction. This methodology achieves moderate performance, up to 80.3% of accuracy using a single path in differential diagnosis involving Alzheimer-affected subjects versus controls belonging to the Alzheimer's disease neuroimaging initiative (ADNI). PMID:27354189

  12. Circulating Biomarker Panels in Alzheimer's Disease.

    Science.gov (United States)

    Zafari, Sachli; Backes, Christina; Meese, Eckart; Keller, Andreas

    2015-01-01

    The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

  13. Ethical issues in Alzheimer's disease: an overview.

    Science.gov (United States)

    Leuzy, Antoine; Gauthier, Serge

    2012-05-01

    Alzheimer's disease (AD) accounts for the majority of dementia cases and leaves clinicians, patients, family members, caregivers, and researchers faced with numerous ethical issues that vary and evolve as a function of disease stage and severity. While the disclosure of a diagnosis of AD dementia is difficult enough, advances in the neurobiology of AD--embodied in the recent revisions to the AD diagnostic guidelines--have translated into an increasing shift toward the diagnosis being made in its pre-dementia stages, when patients have full insight into their prognosis. Genetic issues in AD are significant in the case of rare families with an early onset (before age 65) form of the disease, owing to the presence of deterministic mutations. While genetic testing for the apolipoprotein E (APOE) gene--a risk factor for sporadic AD--is widely debated, it may become necessary in the context of novel disease-modifying drugs. The current symptomatic drugs--cholinesterase inhibitors (CIs) and the NMDA receptor antagonist memantine--are relatively simple to use but their access is limited in many countries by economic considerations and therapeutic nihilism. Although their efficacy is modest, they influence the design of protocols for new drugs since placebo treatment in clinical trials involving patients with established dementia is rarely allowed beyond 3 months. Driving privileges are lost in the moderate stages of dementia, with this decision ideally reached using a standardized assessment algorithm. Physical restraints are still overused in moderate-to-severe stages, but the alternative non-pharmacological therapies and caregiver training programs are not yet fully validated using randomized studies. End-of-life care is slowly moving towards a palliative care approach similar to that for end-stage cancer. There will be new drugs in the near future, some of which will delay progression from prodromal stages to dementia, but their use will require careful stopping rules

  14. Neuronal histamine and cognitive symptoms in Alzheimer's disease.

    Science.gov (United States)

    Zlomuzica, Armin; Dere, Dorothea; Binder, Sonja; De Souza Silva, Maria Angelica; Huston, Joseph P; Dere, Ekrem

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'.

  15. The Role of Mast Cells in Alzheimer's Disease.

    Science.gov (United States)

    Shaik-Dasthagirisaheb, Yasdani B; Conti, Pio

    2016-01-01

    Immunity and inflammation are deeply involved in Alzheimer's disease. The most important properties of pathological Alzheimer's disease are the extracellular deposits of amyloid â-protein plaque aggregates along with other unknown mutated proteins, which are implicated in immunity and inflammation. Mast cells are found in the brain of all mammalian species and in the periphery, and their biological mediators, including cytokines/chemokines, arachidonic acid products and stored enzymes, play an import role in Alzheimer's disease. Cytokines/chemokines, which are generated mostly by microglia and astrocytes in Alzheimer's disease, contribute to nearly every aspect of neuroinflammation and amyloid â-protein plaque aggregates may induce in mast cells the release of a plethora of mediators, including pro-inflammatory cytokines/chemokines such as interleukin-1, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, vascular endothelial growth factor, transforming growth factor beta, CXCL8 and CCL2-3-4. These proinflammatory cytokines/chemokines are prominent mediators of neuroinflammation in brain disorders such as Alzheimer's disease, and their inhibition may be associated with improved recovery. In this review, we summarize the current knowledge regarding the roles of mast cell mediators (stored and de novo synthesis) in the pathogenesis of Alzheimer's disease. PMID:27629855

  16. The Search for Biomarkers in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-04-01

    Full Text Available BACKGROUND: As population demographic shift and the number of individuals with Alzheimer Disease (AD continue to increase, the challenge is to develop targeted, effective treatments and our ability to recognize early symptoms. In view of this, the need for specific AD biomarker is crucial. CONTENT: In recent years it has become evident that CSF concentrations of some brain-specific proteins are related to underlying disease pathogenesis and may therefore aid clinical investigation. Among several, we have focused on three candidates that have been suggested to fulfil the requirements for biomarkers of AD: β-amyloid 42 (Aβ42, total Tau (T-tau and tau phosphorylated at various epitopes (P-tau. An increasing number of studies suggest that supplementary use of these CSF markers, preferably in combination, adds to the accuracy of an AD diagnosis. More recently visinin-like protein (VLP-1, a marker for neuronal cell injury has been studied. CSF VLP-1 concentrations were 50% higher in AD patients than in the control population. SUMMARY: The number of studies aimed at the identification of new biomarkers for AD is expected to increase rapidly, not only because of the increasing insights into the pathological mechanisms underlying this disease, but also because new therapies have been developed or are under consideration now, which warrant an early and specific diagnosis for effective treatment of the patients. KEYWORDS: dementia, amyloid plaque, neurofibrillary tangels, amyloid β-peptide 42 (Aβ42, total tau (T-tau, phosphorylated tau (P-tau, visinin–like protein 1 (VLP-1.

  17. Weak central coherence in patients with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Selina M(a)rdh

    2013-01-01

    Central coherence refers to the ability to interpret details of information into a whole. To date, the concept of central coherence is mainly used in research of autism, Asperger's syndrome and recently in the research on eating disorders. The main purpose of the present study was to examine central coherence in patients with Alzheimer's disease. Nine Alzheimer's disease patients and ten age- and gender-matched control subjects, who differed significantly in neurological assessment, were shown a picture of a fire. Compared to control subjects, the Alzheimer's disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire. In conclusion, patients with Alzheimer's disease are at the weak end of central coherence, and hence suffer from a fragmented view of their surroundings. The findings have important clinical implications for the understanding of patients with Alzheimer's diseaseand also for the possibility of caregivers to meet the Alzheimer's disease individual in an appropriate way in the everyday care.

  18. Transcranial Magnetic Stimulation Studies in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Andrea Guerra

    2011-01-01

    Full Text Available Although motor deficits affect patients with Alzheimer's disease (AD only at later stages, recent studies demonstrated that primary motor cortex is precociously affected by neuronal degeneration. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries, thereby maintaining motor performances in daily living. Effectively several transcranial magnetic stimulation (TMS studies have demonstrated that cortical excitability is enhanced in AD and primary motor cortex presents functional reorganization. Although the best hypothesis for the pathogenesis of AD remains the degeneration of cholinergic neurons in specific regions of the basal forebrain, the application of specific TMS protocols pointed out a role of other neurotransmitters. The present paper provides a perspective of the TMS techniques used to study neurophysiological aspects of AD showing also that, based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological and pathological brain aging at least at the group level. Moreover repetitive TMS might become useful in the rehabilitation of AD patients. Finally integrated approaches utilizing TMS together with others neuro-physiological techniques, such as high-density EEG, and structural and functional imaging as well as biological markers are proposed as promising tool for large-scale, low-cost, and noninvasive evaluation of at-risk populations.

  19. Auditory confrontation naming in Alzheimer's disease.

    Science.gov (United States)

    Brandt, Jason; Bakker, Arnold; Maroof, David Aaron

    2010-11-01

    Naming is a fundamental aspect of language and is virtually always assessed with visual confrontation tests. Tests of the ability to name objects by their characteristic sounds would be particularly useful in the assessment of visually impaired patients, and may be particularly sensitive in Alzheimer's disease (AD). We developed an auditory naming task, requiring the identification of the source of environmental sounds (i.e., animal calls, musical instruments, vehicles) and multiple-choice recognition of those not identified. In two separate studies mild-to-moderate AD patients performed more poorly than cognitively normal elderly on the auditory naming task. This task was also more difficult than two versions of a comparable visual naming task, and correlated more highly with Mini-Mental State Exam score. Internal consistency reliability was acceptable, although ROC analysis revealed auditory naming to be slightly less successful than visual confrontation naming in discriminating AD patients from normal participants. Nonetheless, our auditory naming task may prove useful in research and clinical practice, especially with visually impaired patients. PMID:20981630

  20. Cannabinoids in late-onset Alzheimer's disease.

    Science.gov (United States)

    Ahmed, Aia; van der Marck, M A; van den Elsen, Gah; Olde Rikkert, Mgm

    2015-06-01

    Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. In addition, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety, and pharmacokinetics of cannabinoid-based drugs in older people with dementia. PMID:25788394

  1. Retrieval monitoring and anosognosia in Alzheimer's disease.

    Science.gov (United States)

    Gallo, David A; Chen, Jennifer M; Wiseman, Amy L; Schacter, Daniel L; Budson, Andrew E

    2007-09-01

    This study explored the relationship between episodic memory and anosognosia (a lack of deficit awareness) among patients with mild Alzheimer's disease (AD). Participants studied words and pictures for subsequent memory tests. Healthy older adults made fewer false recognition errors when trying to remember pictures compared with words, suggesting that the perceptual distinctiveness of picture memories enhanced retrieval monitoring (the distinctiveness heuristic). In contrast, although participants with AD could discriminate between studied and nonstudied items, they had difficulty recollecting the specific presentation formats (words or pictures), and they had limited use of the distinctiveness heuristic. Critically, the demands of the memory test modulated the relationship between memory accuracy and anosognosia. Greater anosognosia was associated with impaired memory accuracy when participants with AD tried to remember words but not when they tried to remember pictures. These data further delineate the retrieval monitoring difficulties among individuals with AD and suggest that anosognosia measures are most likely to correlate with memory tests that require the effortful retrieval of nondistinctive information. PMID:17784804

  2. Alzheimer's disease: inside, outside, upside down.

    Science.gov (United States)

    Yan, S D; Schmidt, A M; Stern, D

    2001-01-01

    Neurotoxicity of beta-amyloid peptide (A beta) in Alzheimer's disease (AD) is usually thought to arise from the nonspecific effects of high concentrations of A beta on vulnerable neurons, resulting in membrane destabilization and increasing intracellular calcium concentration. This review advances the hypothesis that at early stages of AD, when A beta is present in lower amounts, its ability to perturb the function of cellular targets is mediated by specific cofactors present on the cell surface and intracellularly. Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor which binds A beta and amplifies its effects on cells in the nanomolar range. The intracellular enzyme A beta-binding alcohol dehydrogenase (ABAD) is likely to engage nascent A beta formed in the endoplasmic reticulum, and to mediate cell stress from this site. The analysis of A beta interaction with RAGE and ABAD, as well as other cofactors, provides insight into new mechanisms and, potentially, identifies therapeutic targets relevant to neuronal dysfunction in AD. PMID:11447831

  3. Cranial CT frindings of familial Alzheimer's disease

    International Nuclear Information System (INIS)

    Three cases of familial Alzheimer's disease were reported. The patients had an average of 41 years, and developed memory disturbance and pyramidal tract syndromes. Two had disturbance of gait and showed cerebellar symptoms. All three patients had hypotension, but had no hypotensive episodes, and no change in character or loss of character. Their IQ was extremely low, and encephalograms had delta theta waves dominant in right frontal region in one case, and general delta theta waves in the other two cases. Brain scintigraphy showed reflux to ventricle in case 2, but not in case 1. Cerebrospinal fluid was normal in all three cases, and chromosomes of cases 1 and 2 were normal 46 XY. CT scan showed that the cerebral cortex of all three patients was markedly shrunken, the sulci were enlarged and the ventricle was enlarged without being extremely rounded; the degree of cerebral atrophy according to Huckman et al. was mild in case 1 and moderate in cases 2 and 3. Slight cerebellar atrophy was detected in case 3. (Kaihara, S.)

  4. Spatial Navigation in Preclinical Alzheimer's Disease.

    Science.gov (United States)

    Allison, Samantha L; Fagan, Anne M; Morris, John C; Head, Denise

    2016-02-01

    Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer's disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n = 42), clinically normal with preclinical AD (n = 13), and early-stage symptomatic AD (n = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. PMID:26967209

  5. Spatial Navigation in Preclinical Alzheimer's Disease

    Science.gov (United States)

    Allison, Samantha L.; Fagan, Anne M.; Morris, John C.; Head, Denise

    2016-01-01

    Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer's disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n = 42), clinically normal with preclinical AD (n = 13), and early-stage symptomatic AD (n = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. PMID:26967209

  6. Common polygenic variation enhances risk prediction for Alzheimer's disease.

    Science.gov (United States)

    Escott-Price, Valentina; Sims, Rebecca; Bannister, Christian; Harold, Denise; Vronskaya, Maria; Majounie, Elisa; Badarinarayan, Nandini; Morgan, Kevin; Passmore, Peter; Holmes, Clive; Powell, John; Brayne, Carol; Gill, Michael; Mead, Simon; Goate, Alison; Cruchaga, Carlos; Lambert, Jean-Charles; van Duijn, Cornelia; Maier, Wolfgang; Ramirez, Alfredo; Holmans, Peter; Jones, Lesley; Hardy, John; Seshadri, Sudha; Schellenberg, Gerard D; Amouyel, Philippe; Williams, Julie

    2015-12-01

    The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample. The disease prediction accuracy was investigated in a subset of the IGAP data, a sample of 3049 cases and 1554 controls (for whom APOE genotype data were available) by means of sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and positive and negative predictive values. We observed significant evidence for a polygenic component enriched in Alzheimer's disease (P = 4.9 × 10(-26)). This enrichment remained significant after APOE and other genome-wide associated regions were excluded (P = 3.4 × 10(-19)). The best prediction accuracy AUC = 78.2% (95% confidence interval 77-80%) was achieved by a logistic regression model with APOE, the polygenic score, sex and age as predictors. In conclusion, Alzheimer's disease has a significant polygenic component, which has predictive utility for Alzheimer's disease risk and could be a valuable research tool complementing experimental designs, including preventative clinical trials, stem cell selection and high/low risk clinical studies. In modelling a range of sample disease prevalences, we found that polygenic scores almost doubles case prediction from chance with increased prediction at polygenic extremes. PMID:26490334

  7. White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI

    Directory of Open Access Journals (Sweden)

    Aikaterini Xekardaki

    2011-01-01

    Full Text Available Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI, a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease.

  8. Self, cortical midline structures and the resting state: Implications for Alzheimer's disease.

    Science.gov (United States)

    Weiler, Marina; Northoff, Georg; Damasceno, Benito Pereira; Balthazar, Marcio Luiz Figueredo

    2016-09-01

    Different aspects of the self have been reported to be affected in many neurological or psychiatric diseases such as Alzheimer's disease (AD), including mainly higher-level cognitive self-unawareness. This higher sense of self-awareness is most likely related to and dependent on episodic memory, due to the proper integration of ourselves in time, with a permanent conservation of ourselves (i.e., sense of continuity across time). Reviewing studies in this field, our objective is thus to raise possible explanations, especially with the help of neuroimaging studies, for where such self-awareness deficits originate in AD patients. We describe not only episodic (and autobiographical memory) impairment in patients, but also the important role of cortical midline structures, the Default Mode Network, and the resting state (intrinsic brain activity) for the processing of self-related information.

  9. 2009 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2009-05-01

    Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States, and the fifth leading cause of death in Americans aged 65 and older. Whereas other major causes of death have been on the decrease, deaths attributable to AD have been rising dramatically. Between 2000 and 2006, heart-disease deaths decreased nearly 12%, stroke deaths decreased 18%, and prostate cancer-related deaths decreased 14%, whereas deaths attributable to AD increased 47%. An estimated 5.3 million Americans have AD; the approximately 200,000 persons under age 65 years with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050, this time is expected to decrease to every 33 seconds. Over the coming decades, the "baby-boom" population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Significant cost implications related to AD and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (e.g., decreased business productivity) costs. Not included in these figures is the $94 billion in unpaid services to individuals with AD provided annually by an estimated 10 million caregivers. Mild cognitive impairment (MCI) is an important component in the continuum from healthy cognition to dementia. Understanding which individuals with MCI are at highest risk for eventually developing AD is key to our ultimate goal of preventing AD. This report provides information meant to increase an understanding of the public-health impact of AD, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. This report also sets the stage for a better understanding of the relationship between MCI and AD. PMID:19426951

  10. 2012 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2012-01-01

    This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD). Topics addressed include incidence, prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society. The report also explores issues that arise when people with AD and other dementias live alone. The characteristics, risks, and unmet needs of this population are described. An estimated 5.4 million Americans have AD, including approximately 200,000 age disease, stroke, and prostate cancer decreased by 13%, 20%, and 8%, respectively, whereas the proportion due to AD increased by 66%. In 2011, more than 15 million family members and other unpaid caregivers provided an estimated 17.4 billion hours of care to people with AD and other dementias, a contribution valued at more than $210 billion. Medicare payments for services to beneficiaries age ≥65 years with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. In 2012, payments for health care, long-term care, and hospice services for people age ≥65 years with AD and other dementias are expected to be $200 billion (not including the contributions of unpaid caregivers). An estimated 800,000 people with AD (one in seven) live alone, and up to half of them do not have an identifiable caregiver. People with dementia who live alone are exposed to risks that exceed the risks encountered by people with dementia who live with others, including inadequate self-care, malnutrition, untreated medical conditions, falls, wandering from home unattended, and accidental deaths. PMID:22404854

  11. Biomedicine and Informatics Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Kang Cheng

    2007-01-01

    Full Text Available In a perspective of biomedicine and informatics, the mechanism of Alzheimer's, senile amnesia, or other aging-associated and cognitive impairment related diseases involve four important informative processing procedures: propagation, consolidation, retrieval and cognition, In this study, we systematically model the four procedures based on published experimental data. When modeling the propagation, we develop an equivalent circuit of biological membrane to describe how the neuron signals are propagated, attenuated, compensated, transferred, oscillated and filtered; and how wrong signals are related to the diseases. Our circuit involves complex admittances, resonance angular frequencies, propagating constants, active pump currents, transfer functions in frequency domain and memory functions in time domain. Our circuit explains recurrent of brain neurons and clinical EEG frequencies as well as represents an encoding of current or electric field intensity (EFI. When modeling the consolidation and the retrieval of long term memory (LTM, we emphasize the EFI consists of a non conservative electric field intensity (NCEFI and a conservative electric field intensity (CEFI. It is mostly a NCEFI of acquired information to evoke an informative flow: from the inherited or mutant DNA to the transcribed RNA, from the transcribed RNA to the translated proteins. Some new synthesized proteins relate to the memory functions. The charges of the proteins and the memory functions mostly store the LTM and play an important role during the LTM retrieval. When modeling the cognition in working memory (WM, our model demonstrates: if a sum of two sets of EFI signals is enhanced positively (or negatively, at a sub-cellular level (especially at the axon hillock, the sum supports a positive (or negative cognition; otherwise, the sum tends to be no cognition. A set of related brain neurons in WM work organically to vote, by EFI signal outputs through their axons, if they

  12. Inflammaging as a prodrome to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Rrapo Elona

    2008-11-01

    Full Text Available Abstract Recently, the term "inflammaging" was coined by Franceshci and colleagues to characterize a widely accepted paradigm that ageing is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses. Inflammaging differs significantly from the traditional five cardinal features of acute inflammation in that it is characterized by a relative decline in adaptive immunity and T-helper 2 responses and is associated with increased innate immunity by cells of the mononuclear phagocyte lineage. While the over-active innate immunity characteristic of inflammaging may remain subclinical in many elderly individuals, a portion of individuals (postulated to have a "high responder inflammatory genotype" may shift from a state of "normal" or "subclinical" inflammaging to one or more of a number of age-associated diseases. We and others have found that IFN-γ and other pro-inflammatory cytokines interact with processing and production of Aβ peptide, the pathological hallmark feature of Alzheimer's disease (AD, suggesting that inflammaging may be a "prodrome" to AD. Although conditions of enhanced innate immune response with overproduction of pro-inflammatory proteins are associated with both healthy aging and AD, it is suggested that those who age "well" demonstrate anti-inflammaging mechanisms and biomarkers that likely counteract the adverse immune response of inflammaging. Thus, opposing the features of inflammaging may prevent or treat the symptoms of AD. In this review, we fully characterize the aging immune system. In addition, we explain how three novel treatments, (1 human umbilical cord blood cells (HUCBC, (2 flavanoids, and (3 Aβ vaccination oppose the forces of inflammaging and AD-like pathology in various mouse models.

  13. Developmental Disabilities and Alzheimer's Disease...What You Should Know.

    Science.gov (United States)

    Arc, Arlington, TX.

    This booklet provides an overview of Alzheimer's disease along with a description of the disease, how to find out if someone has it, and how it affects adults with developmental disabilities. It also provides information on what to do and suggests where to seek help. Specific sections discuss: (1) the etiology of the disease; (2) symptoms of…

  14. Towards an All-Polymer Biosensor for Early Alzheimer's Disease

    DEFF Research Database (Denmark)

    Christiansen, Nikolaj Ormstrup; Heegaard, Niels

    Alzheimer's disease (AD) is quickly evolving into one of the biggest and most costly health issues in Europe and the United States. AD is a protein misfolding disease, caused by accumulation of abnormally folded β-amyloid and tau protein in the brain. The build-up of protein is believed to degene......Alzheimer's disease (AD) is quickly evolving into one of the biggest and most costly health issues in Europe and the United States. AD is a protein misfolding disease, caused by accumulation of abnormally folded β-amyloid and tau protein in the brain. The build-up of protein is believed...

  15. Impact of Neuroprotection on Incidence of Alzheimer's Disease

    OpenAIRE

    Raúl de la Fuente-Fernández

    2006-01-01

    Converging evidence suggests that high levels of education and intellectual activity increase the cognitive reserve and reduce the risk of dementia. However, little is known about the impact that different neuroprotective strategies may have on the incidence of Alzheimer's disease. Using a simple mathematical regression model, it is shown here that age-specific counts of basic cognitive units (surrogate of neurons or synapses) in the normal population can be estimated from Alzheimer's inciden...

  16. Alzheimer's Disease Diagnostics by Adaptation of 3D Convolutional Network

    OpenAIRE

    Hosseini-Asl, Ehsan; Keynto, Robert; El-Baz, Ayman

    2016-01-01

    Early diagnosis, playing an important role in preventing progress and treating the Alzheimer\\{'}s disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposed to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capt...

  17. Discriminative multi-task feature selection for multi-modality classification of Alzheimer's disease.

    Science.gov (United States)

    Ye, Tingting; Zu, Chen; Jie, Biao; Shen, Dinggang; Zhang, Daoqiang

    2016-09-01

    Recently, multi-task based feature selection methods have been used in multi-modality based classification of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). However, in traditional multi-task feature selection methods, some useful discriminative information among subjects is usually not well mined for further improving the subsequent classification performance. Accordingly, in this paper, we propose a discriminative multi-task feature selection method to select the most discriminative features for multi-modality based classification of AD/MCI. Specifically, for each modality, we train a linear regression model using the corresponding modality of data, and further enforce the group-sparsity regularization on weights of those regression models for joint selection of common features across multiple modalities. Furthermore, we propose a discriminative regularization term based on the intra-class and inter-class Laplacian matrices to better use the discriminative information among subjects. To evaluate our proposed method, we perform extensive experiments on 202 subjects, including 51 AD patients, 99 MCI patients, and 52 healthy controls (HC), from the baseline MRI and FDG-PET image data of the Alzheimer's Disease Neuroimaging Initiative (ADNI). The experimental results show that our proposed method not only improves the classification performance, but also has potential to discover the disease-related biomarkers useful for diagnosis of disease, along with the comparison to several state-of-the-art methods for multi-modality based AD/MCI classification. PMID:26311394

  18. Discriminative multi-task feature selection for multi-modality classification of Alzheimer's disease.

    Science.gov (United States)

    Ye, Tingting; Zu, Chen; Jie, Biao; Shen, Dinggang; Zhang, Daoqiang

    2016-09-01

    Recently, multi-task based feature selection methods have been used in multi-modality based classification of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). However, in traditional multi-task feature selection methods, some useful discriminative information among subjects is usually not well mined for further improving the subsequent classification performance. Accordingly, in this paper, we propose a discriminative multi-task feature selection method to select the most discriminative features for multi-modality based classification of AD/MCI. Specifically, for each modality, we train a linear regression model using the corresponding modality of data, and further enforce the group-sparsity regularization on weights of those regression models for joint selection of common features across multiple modalities. Furthermore, we propose a discriminative regularization term based on the intra-class and inter-class Laplacian matrices to better use the discriminative information among subjects. To evaluate our proposed method, we perform extensive experiments on 202 subjects, including 51 AD patients, 99 MCI patients, and 52 healthy controls (HC), from the baseline MRI and FDG-PET image data of the Alzheimer's Disease Neuroimaging Initiative (ADNI). The experimental results show that our proposed method not only improves the classification performance, but also has potential to discover the disease-related biomarkers useful for diagnosis of disease, along with the comparison to several state-of-the-art methods for multi-modality based AD/MCI classification.

  19. Fuzzy Computer-Aided Alzheimer's Disease Diagnosis Based on MRI Data.

    Science.gov (United States)

    Krashenyi, Igor; Ramírez, Javier; Popov, Anton; Górriz, Juan Manuel; The Alzheimer's Disease Neuroimaging Initiative

    2016-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system that has no cure and leads to death. One of the most prevalent tools for AD diagnosis is magnetic resonance imaging (MRI), because of its capability to visualize brain anatomical structures. There is a variety of classification methods for automatic diagnosis of AD, such as support vector machines, genetic algorithms, Bayes classifiers, neural networks, random forests, etc., but none of them provides robust information about the stage of the AD, they can just reveal the presence of disease. In this paper, a new approach for classification of MRI images using a fuzzy inference system is proposed. Two statistical moments (mean and standard deviation) of 116 anatomical regions of interests (ROIs) are used as input features for the classification system. A t-test feature selection method is used to identify the most discriminative ROIs. In order to evaluate the proposed system, MRI images from a database consisting of 818 subjects (229 normal, 401 mild cognitive impairment and 188 AD subjects) collected from the Alzheimer's disease neuroimaging initiative (ADNI) is analyzed. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) of the proposed fuzzy inference system fed by statistical input features are employed as the evaluation criteria with k-fold cross validation. The proposed system yields promising results in normal vs. AD classification with AUC of 0.99 on the training set and 0.8622±0.0033 on the testing set. PMID:26971942

  20. Alzheimer's Project

    Medline Plus

    Full Text Available ... and the effects this debilitating and fatal disease has on those with Alzheimer's and their families. September ... Alzheimer's care, support and research, the Alzheimer's Association has been an active partner in "THE ALZHEIMER'S PROJECT," ...

  1. Alzheimer's Association

    Science.gov (United States)

    ... will not share your information. * Required. View archives. Alzheimer's impact is growing Alzheimer's disease is the sixth- ... Last Updated: Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association advances research ...

  2. Impaired lysosomal cobalamin transport in Alzheimer's disease.

    Science.gov (United States)

    Zhao, Hua; Li, Hongyun; Ruberu, Kalani; Garner, Brett

    2015-01-01

    Cobalamin (vitamin B12) is required for erythrocyte formation and DNA synthesis and it plays a crucial role in maintaining neurological function. As a coenzyme for methionine synthase and methylmalonyl-CoA mutase, cobalamin utilization depends on its efficient transit through the intracellular lysosomal compartment and subsequent delivery to the cytosol and mitochondria. Lysosomal function deteriorates in Alzheimer's disease (AD). Lysosomal acidification is defective in AD and lysosomal proteolysis is disrupted by AD-related presenilin 1 mutation. In this study, we propose that AD related lysosomal dysfunction may impair lysosomal cobalamin transport. The experiments use in vitro and in vivo models of AD to define how lysosomal dysfunction directly affects cobalamin utilization. SH-SY5Y-AβPP mutant cells were treated with a proteasome inhibitor to induce lysosomal amyloid-β accumulation. We metabolically labeled these cells with [57Co] cobalamin and isolated purified lysosomes, mitochondria, and cytosol fractions. The results indicated that proteasome inhibition was associated with lysosomal amyloid-β accumulation and a doubling of lysosomal [57Co] cobalamin levels. We also used AβPPxPS1 transgenic AD mice that were intraperitoneally injected with [57Co] cobalamin. The amount of [57Co] cobalamin in the major organs of these mice was measured and the subcellular [57Co] cobalamin distribution in the brain was assessed. The results demonstrated that lysosomal [57Co] cobalamin level was significantly increased by 56% in the AβPPxPS1 AD mouse brains as compared to wild type control mice. Together these data provide evidence that lysosomal cobalamin may be impaired in AD in association with amyloid-β accumulation. PMID:25125476

  3. Microglial dysfunction connects depression and Alzheimer's disease.

    Science.gov (United States)

    Santos, Luís Eduardo; Beckman, Danielle; Ferreira, Sergio T

    2016-07-01

    Alzheimer's disease (AD) and major depressive disorder (MDD) are highly prevalent neuropsychiatric conditions with intriguing epidemiological overlaps. Depressed patients are at increased risk of developing late-onset AD, and around one in four AD patients are co-diagnosed with MDD. Microglia are the main cellular effectors of innate immunity in the brain, and their activation is central to neuroinflammation - a ubiquitous process in brain pathology, thought to be a causal factor of both AD and MDD. Microglia serve several physiological functions, including roles in synaptic plasticity and neurogenesis, which may be disrupted in neuroinflammation. Following early work on the 'sickness behavior' of humans and other animals, microglia-derived inflammatory cytokines have been shown to produce depressive-like symptoms when administered exogenously or released in response to infection. MDD patients consistently show increased circulating levels of pro-inflammatory cytokines, and anti-inflammatory drugs show promise for treating depression. Activated microglia are abundant in the AD brain, and concentrate around senile plaques, hallmark lesions composed of aggregated amyloid-β peptide (Aβ). The Aβ burden in affected brains is regulated largely by microglial clearance, and the complex activation state of microglia may be crucial for AD progression. Intriguingly, recent reports have linked soluble Aβ oligomers, toxins that accumulate in AD brains and are thought to cause memory impairment, to increased brain cytokine production and depressive-like behavior in mice. Here, we review recent findings supporting the inflammatory hypotheses of AD and MDD, focusing on microglia as a common player and therapeutic target linking these devastating disorders. PMID:26612494

  4. Brain imaging of mild cognitive impairment and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Changhao Yin; Siou Li; Weina Zhao; Jiachun Feng

    2013-01-01

    The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

  5. Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.

    Science.gov (United States)

    Tavares, Eva; Antequera, Desiree; López-González, Irene; Ferrer, Isidro; Miñano, Francisco J; Carro, Eva

    2016-10-01

    Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-β (Aβ), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Aβ-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Aβ-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Aβ-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target. PMID:27497681

  6. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

    Directory of Open Access Journals (Sweden)

    Xiaochuan Wang

    Full Text Available Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.

  7. Preserved painting creativity in an artist with Alzheimer's disease.

    Science.gov (United States)

    Fornazzari, L R

    2005-06-01

    Creativity in any of its forms, either visual, musical, literary or performing arts, may be conceived as a cognitive capability, and should be actively explored in relation to patients with Alzheimer disease and related dementias, even when other cognitive functions do not allow us to even communicate with them. We are reporting the case of a talented artist with the diagnosis of early onset Alzheimer disease (AD) with progressive cognitive impairment but with preservation of her creativity until very late in the course of the disease. PMID:15885044

  8. Alzheimer's Disease in the Danish Malnutrition Period 1999-2007

    DEFF Research Database (Denmark)

    Sparre-Sørensen, Maja; Kristensen, Gustav David Westergaard

    2015-01-01

    BACKGROUND: Several studies published over the last few years have shown that malnutrition is a risk factor for developing and worsening Alzheimer's disease (AD) and that a balanced diet can delay the onset of the disease. During the period from January 1999 to January 2007, a statistically...... from AD associated with the period when the general nutritional state among the elderly in Denmark worsened (from 1999 to 2007). CONCLUSION: The study concludes that the malnutrition period resulted in an excess death rate from Alzheimer's disease. All in all, a total of 345 extra lives were lost...

  9. The S100B/RAGE Axis in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Estelle Leclerc

    2010-01-01

    Full Text Available Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A, the Advanced Glycation Endproducts (AGEs, or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

  10. Impact of neuroprotection on incidence of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Raúl de la Fuente-Fernández

    Full Text Available Converging evidence suggests that high levels of education and intellectual activity increase the cognitive reserve and reduce the risk of dementia. However, little is known about the impact that different neuroprotective strategies may have on the incidence of Alzheimer's disease. Using a simple mathematical regression model, it is shown here that age-specific counts of basic cognitive units (surrogate of neurons or synapses in the normal population can be estimated from Alzheimer's incidence rates. Hence, the model can be used to test the effect of neuroprotection on Alzheimer's incidence. It was found that the number of basic cognitive units decreases with age, but levels off in older people. There were no gender differences after correcting for survival. The model shows that even modest neuroprotective effects on basic cognitive units can lead to dramatic reductions in the number of Alzheimer's cases. Most remarkably, a 5% increase in the cognitive reserve would prevent one third of Alzheimer's cases. These results suggest that public health policies aimed at increasing the cognitive reserve in the general population (e.g., implementing higher levels of education are likely the most effective strategy for preventing Alzheimer's disease.

  11. Deformation-based atrophy computation by surface propagation and its application to Alzheimer's disease.

    Science.gov (United States)

    Pai, Akshay; Sporring, Jon; Darkner, Sune; Dam, Erik B; Lillholm, Martin; Jørgensen, Dan; Oh, Joonmi; Chen, Gennan; Suhy, Joyce; Sørensen, Lauge; Nielsen, Mads

    2016-01-01

    Obtaining regional volume changes from a deformation field is more precise when using simplex counting (SC) compared with Jacobian integration (JI) due to the numerics involved in the latter. Although SC has been proposed before, numerical properties underpinning the method and a thorough evaluation of the method against JI is missing in the literature. The contributions of this paper are: (a) we propose surface propagation (SP)-a simplification to SC that significantly reduces its computational complexity; (b) we will derive the orders of approximation of SP which can also be extended to SC. In the experiments, we will begin by empirically showing that SP is indeed nearly identical to SC, and that both methods are more stable than JI in presence of moderate to large deformation noise. Since SC and SP are identical, we consider SP as a representative of both the methods for a practical evaluation against JI. In a real application on Alzheimer's disease neuroimaging initiative data, we show the following: (a) SP produces whole brain and medial temporal lobe atrophy numbers that are significantly better than JI at separating between normal controls and Alzheimer's disease patients; (b) SP produces disease group atrophy differences comparable to or better than those obtained using FreeSurfer, demonstrating the validity of the obtained clinical results. Finally, in a reproducibility study, we show that the voxel-wise application of SP yields significantly lower variance when compared to JI. PMID:27014717

  12. 2010 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2010-03-01

    Alzheimer's disease (AD) is the seventh leading cause of all deaths in the United States and is virtually tied with the sixth leading cause of death-diabetes. AD is the fifth leading cause of death in Americans aged 65 and older. Although other major causes of death have been on the decrease, deaths because of AD have been rising dramatically. Between 2000 and 2006, heart disease deaths decreased 11.1%, stroke deaths decreased 18.2%, and prostate cancer-related deaths decreased 8.7%, whereas deaths because of AD increased 46.1%. Older African-Americans and Hispanics are more likely than older white Americans to have AD or other dementia. Current estimates are that African-Americans are about 2 times more likely, and Hispanics about 1.5 times more likely, than their white counterparts to have these conditions. However, the relationship of race and ethnicity to the development of AD and other dementias is complex and not fully understood. In 2009, nearly 11 million family and other unpaid caregivers provided an estimated 12.5 billion hours of care to persons with AD and other dementias; this care is valued at nearly $144 billion. Medicare payments for services to beneficiaries aged 65 years and older with AD and other dementias are three times higher than for beneficiaries without these conditions. Total payments for 2010 for health care and long-term care services for people aged 65 and older with AD and other dementias are expected to be $172 billion (not including the contributions of unpaid caregivers). An estimated 5.3 million Americans have AD; approximately 200,000 persons under age 65 with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050 the time of every 70 seconds is expected to decrease to every 33 seconds. Over the coming decades, the baby boom population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a

  13. 2011 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2011-03-01

    Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States and is the fifth leading cause of death in Americans aged ≥65 years. Although other major causes of death have been on the decrease, deaths because of AD have been rising dramatically. Between 2000 and 2008 (preliminary data), heart disease deaths decreased by 13%, stroke deaths by 20%, and prostate cancer-related deaths by 8%, whereas deaths because of AD increased by 66%. An estimated 5.4 million Americans have AD; approximately 200,000 people aged <65 years with AD comprise the younger-onset AD population. Every 69 seconds, someone in America develops AD; by 2050, the time is expected to accelerate to every 33 seconds. Over the coming decades, the baby boom population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Dramatic increases in the numbers of "oldest-old" (those aged ≥85 years) across all racial and ethnic groups will also significantly affect the numbers of people living with AD. In 2010, nearly 15 million family and other unpaid caregivers provided an estimated 17 billion hours of care to people with AD and other dementias, a contribution valued at more than $202 billion. Medicare payments for services to beneficiaries aged ≥65 years with AD and other dementias are almost 3 times higher than for beneficiaries without these conditions. Total payments in 2011 for health care, long-term care, and hospice services for people aged ≥65years with AD and other dementias are expected to be $183 billion (not including the contributions of unpaid caregivers). This report provides information to increase understanding of the public health effect of AD, including incidence and prevalence, mortality, health expenditures and costs of care, and effect on caregivers and society in general. The report also examines the

  14. Stem cell therapy for Alzheimer's disease.

    Science.gov (United States)

    Abdel-Salam, Omar M E

    2011-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (Abeta) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain of mice or rats were mostly followed by their incorporation into the host parenchyma and differentiation into functional neural lineages. In the lesioned brain, stem cells exhibited targeted migration towards the damaged regions of the brain, where they engrafted, proliferated and matured into functional neurones. Neural precursor cells can be intravenously administered and yet migrate into brain damaged areas and induce functional recovery. Observations in animal models of AD have provided evidence that transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory deficits. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines and neuronal apoptotic death. Stem cells could also be genetically modified to express growth factors into the brain. In the last years, evidence indicated that the adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute to the

  15. Time estimation in mild Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Nichelli Paolo

    2009-07-01

    Full Text Available Abstract Background Time information processing relies on memory, which greatly supports the operations of hypothetical internal timekeepers. Scalar Expectancy Theory (SET postulates the existence of a memory component that is functionally separated from an internal clock and other processing stages. SET has devised several experimental procedures to map these cognitive stages onto cerebral regions and neurotransmitter systems. One of these, the time bisection procedure, has provided support for a dissociation between the clock stage, controlled by dopaminergic systems, and the memory stage, mainly supported by cholinergic neuronal networks. This study aimed at linking the specific memory processes predicted by SET to brain mechanisms, by submitting time bisection tasks to patients with probable Alzheimer's disease (AD, that are known to present substantial degeneration of the fronto-temporal regions underpinning memory. Methods Twelve mild AD patients were required to make temporal judgments about intervals either ranging from 100 to 600 ms (short time bisection task or from 1000 to 3000 ms (long time bisection task. Their performance was compared with that of a group of aged-matched control participants and a group of young control subjects. Results Long time bisection scores of AD patients were not significantly different from those of the two control groups. In contrast, AD patients showed increased variability (as indexed by increased WR values in timing millisecond durations and a generalized inconsistency of responses over the same interval in both the short and long bisection tasks. A similar, though milder, decreased millisecond interval sensitivity was found for elderly subjects. Conclusion The present results, that are consistent with those of previous timing studies in AD, are interpreted within the SET framework as not selectively dependent on working or reference memory disruptions but as possibly due to distortions in different

  16. Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease.

    Science.gov (United States)

    Alexopoulos, Panagiotis; Kriett, Laura; Haller, Bernhard; Klupp, Elisabeth; Gray, Katherine; Grimmer, Timo; Laskaris, Nikolaos; Förster, Stefan; Perneczky, Robert; Kurz, Alexander; Drzezga, Alexander; Fellgiebel, Andreas; Yakushev, Igor

    2014-11-01

    New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen κ, 0.24-0.34), in accord with a high rate of conflicting findings (26%-41%). Neither diagnosis nor APOE ε4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement tended to be higher in individuals with abnormal versus normal CSF β-amyloid (Aβ1-42) levels. Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.

  17. Alzheimer's disease and Down's syndrome: treating two paths to dementia

    NARCIS (Netherlands)

    Weksler, M.E.; Szabo, P.; Relkin, N.R.; Reidenberg, M.M.; Weksler, B.B.; Coppus, A.M.W.

    2013-01-01

    Successful therapy of dementia, like any disease, depends upon understanding its pathogenesis. This review contrasts the dominant pathways to dementia which differ in Alzheimer's disease (AD) and in Down's syndrome (DS). Impaired clearance of neurotoxic amyloid beta peptides (Abeta) leads to dementi

  18. Alzheimer's Disease. LC Science Tracer Bullet 87-2.

    Science.gov (United States)

    Sammons, Vivian O., Comp.

    Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

  19. Botanics: a potential source of new therapies for Alzheimer's disease?

    OpenAIRE

    Syad AN; Devi KP

    2014-01-01

    Arif Nisha Syad, Kasi Pandima Devi Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India Abstract: Alzheimer's disease is an age-related, complex neurodegenerative disorder characterized by loss of memory and impairment of multiple cognitive functions. Several factors contribute to the progression and development of the disease including amyloid beta accumulation, neurofibrillary tangle formation, cholinergic deficit, oxidative stress, neuroinflammation, and apop...

  20. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    Science.gov (United States)

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows investigations without artificial overexpression of inherited Alzheimer's disease genes. PMID:25991605

  1. Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease.

    Science.gov (United States)

    Kilander, L; Boberg, M; Lithell, H

    1993-04-01

    Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified. PMID:8503259

  2. Alzheimer's disease and Type 2 diabetes mellitus: the cholinesterase connection?

    Directory of Open Access Journals (Sweden)

    Siva Prasad Akula

    2006-11-01

    Full Text Available Abstract Alzheimer's disease and type 2 diabetes mellitus tend to occur together. We sought to identify protein(s common to both conditions that could suggest a possible unifying pathogenic role. Using human neuronal butyrylcholinesterase (AAH08396.1 as the reference protein we used BLAST Tool for protein to protein comparison in humans. We found three groups of sequences among a series of 12, with an E-value between 0–12, common to both Alzheimer's disease and diabetes: butyrylcholinesterase precursor K allele (NP_000046.1, acetylcholinesterase isoform E4-E6 precursor (NP_000656.1, and apoptosis-related acetylcholinesterase (1B41|A. Butyrylcholinesterase and acetylcholinesterase related proteins were found common to both Alzheimer's disease and diabetes; they may play an etiological role via influencing insulin resistance and lipid metabolism.

  3. Efficacy of psychosocial intervention in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Waldorff, F B; Buss, D V; Eckermann, A;

    2012-01-01

    OBJECTIVE: To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers. DESIGN: Multicentre, randomised, controlled, rater blinded trial. SETTING: Primary care and memory clinics in five...... Danish districts. PARTICIPANTS: 330 outpatients with mild Alzheimer's disease and their 330 primary care givers. INTERVENTIONS: Participating dyads (patient and primary care giver) were randomised to control support during follow-up or to control support plus DAISY intervention (multifaceted and semi...... for attrition (P = 0.0146 and P = 0.0103 respectively). CONCLUSIONS: The multifaceted, semi-tailored intervention with counselling, education, and support for patients with mild Alzheimer's disease and their care givers did not have any significant effect beyond that with well structured follow-up support at 12...

  4. Inhalational Alzheimer's disease: an unrecognized—and treatable—epidemic

    Science.gov (United States)

    Bredesen, Dale E.

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave. PMID:26870879

  5. Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.

    Science.gov (United States)

    Bredesen, Dale E

    2016-02-01

    Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave. PMID:26870879

  6. Fast Parallel Image Registration on CPU and GPU for Diagnostic Classification of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Denis P Shamonin

    2014-01-01

    Full Text Available Nonrigid image registration is an important, but time-consuming taskin medical image analysis. In typical neuroimaging studies, multipleimage registrations are performed, i.e. for atlas-based segmentationor template construction. Faster image registration routines wouldtherefore be beneficial.In this paper we explore acceleration of the image registrationpackage elastix by a combination of several techniques: iparallelization on the CPU, to speed up the cost function derivativecalculation; ii parallelization on the GPU building on andextending the OpenCL framework from ITKv4, to speed up the Gaussianpyramid computation and the image resampling step; iii exploitationof certain properties of the B-spline transformation model; ivfurther software optimizations.The accelerated registration tool is employed in a study ondiagnostic classification of Alzheimer's disease and cognitivelynormal controls based on T1-weighted MRI. We selected 299participants from the publicly available Alzheimer's DiseaseNeuroimaging Initiative database. Classification is performed with asupport vector machine based on gray matter volumes as a marker foratrophy. We evaluated two types of strategies (voxel-wise andregion-wise that heavily rely on nonrigid image registration.Parallelization and optimization resulted in an acceleration factorof 4-5x on an 8-core machine. Using OpenCL a speedup factor of ~2was realized for computation of the Gaussian pyramids, and 15-60 forthe resampling step, for larger images. The voxel-wise and theregion-wise classification methods had an area under thereceiver operator characteristic curve of 88% and 90%,respectively, both for standard and accelerated registration.We conclude that the image registration package elastix wassubstantially accelerated, with nearly identical results to thenon-optimized version. The new functionality will become availablein the next release of elastix as open source under the BSD license.

  7. The Valsalva maneuver and Alzheimer's disease: is there a link?

    Science.gov (United States)

    Wostyn, Peter; Audenaert, Kurt; De Deyn, Peter Paul

    2009-02-01

    Recent research findings provide evidence for Alzheimer's disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. This strengthens the possibility that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to elevated mechanical load. As activities or diseases with significant Valsalva effort can generate increased intracranial pressures, we hypothesize that individuals who frequently perform strong Valsalva maneuvers (e.g., long hours of repetitive heavy lifting, sequences of blows during the playing of a wind instrument, forceful and repetitive cough, bearing-down efforts during parturition) may be more susceptible to developing Alzheimer's disease. In this paper, we discuss three hypotheses about the mechanisms by which extensive use of the Valsalva maneuver might contribute to the neuropathogenesis of Alzheimer's disease: via mechanical stress-induced events in the hippocampus and/or via changes in the secretory process of the choroid plexus and/or via hemodynamic changes in cerebral blood flow. If confirmed, this hypothesis could have implications in clinical practice. PMID:19199876

  8. Bioenergetics breakdown in Alzheimer's disease: targets for new therapies

    OpenAIRE

    Saxena, Uday

    2010-01-01

    Alzheimer's disease is rapidly growing worldwide and yet there is no cure for it. Currently available drugs only provide symptomatic relief and do not intervene in disease process sufficiently enough to prevent or cure it. Characteristic features of this disease are decline in neuronal mass and cognitive functions. The most dominant hypothesis proposed for pathogenesis of this disease is called “amyloid hypothesis". It states that excessive production of amyloid peptides called abeta peptides...

  9. Cerebral microbleeds in early Alzheimer's disease.

    Science.gov (United States)

    Poliakova, T; Levin, O; Arablinskiy, A; Vasenina, E; Zerr, I

    2016-10-01

    We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Addenbrooke's Cognitive Examination (ACE-R), Cambridge Cognitive Examination battery (CAMCOG) (Part 3), Clock Drawing Test, fluency test and the visual memory test (SCT). CSF was examined for standard parameters such as tau, phosphorylated tau, amyloid-β 1-40 and 42 and Qalbumin, in accordance with established protocols and genotype. In 61 patients (45 %), at least 1 CMB was found. Most of the CMBs were described in the amnestic profile (67 %). In 86 % of the cases, multiple CMB were observed. The ratio of Aβ1-40/42 in non-amnestic patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). A notable difference in the albumin ratio as an indicator of the BBB was observed between groups with and without CMB. In the CMP-positive group, the E2 genotype was observed more frequently, and the E4 genotype less frequently, than in the CMB-negative group. Based on the cerebrospinal fluid-serum albumin ratio, we were able to show that patients with CMB present several features of BBB dysfunction. According to logistic regression, the predictive factors for CMB in patients with cognitive decline were age, WMHs score and albumin ratio. We found a significant reduction in the Aβ-amyloid ratio in the non-amnestic profile group with CMB (particularly in the cortical region) in comparison to those without CMB. While this is an interesting finding, its significance needs to be assessed in a prospective follow-up.

  10. Early complement components in Alzheimer's disease brains.

    Science.gov (United States)

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  11. Endothelial progenitor cells with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    KONG Xiao-dong; ZHANG Yun; LIU Li; SUN Ning; ZHANG Ming-yi; ZHANG Jian-ning

    2011-01-01

    Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer's disease (AD).Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD (n=30),patients with vascular dementia (VaD, n=34), and healthy elderly control subjects with normal cognition (n=40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups (P >0.05). The patients with AD showed decreased CD34-positive (CD34+) or CD133-positive (CD133+) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34+CD133+ EPCs(CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P <0.05). In the patients with AD, a lower CD34+CD133+ EPCs count was independently associated with a lower Mini-Mental State Examination score (r=0.514, P=0.004). Patients with VaD also showed a significant decrease in CD34+CD133+ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than

  12. Efficacy of psychosocial intervention in patients with mild Alzheimer's disease: the multicentre, rater blinded, randomised Danish Alzheimer Intervention Study (DAISY)

    DEFF Research Database (Denmark)

    Waldorff, F.B.; Buss, D.V.; Eckermann, A.;

    2012-01-01

    To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers.......To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers....

  13. The Use of Neuroimaging in the Diagnosis of Mitochondrial Disease

    Science.gov (United States)

    Friedman, Seth D.; Shaw, Dennis W. W.; Ishak, Gisele; Gropman, Andrea L.; Saneto, Russell P.

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation…

  14. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold;

    2011-01-01

    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain, such as ......Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain...

  15. The Category Cued Recall test in very mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Mortensen, E.L.; Gade, A.;

    2007-01-01

    Episodic memory tests that measure cued recall may be particularly effective in the diagnosis of early Alzheimer's disease (AD) because they examine both episodic and semantic memory functions. The Category Cued Recall (CCR) test provides superordinate semantic cues at encoding and retrieval......, and high discriminative validity has been claimed for this test. The aim of this study was to investigate the discriminative validity for this test when compared with the 10-word memory list from Alzheimer's Disease Assessment Scale (ADAS-cog) that measures free recall. The clinical diagnosis of AD...

  16. Gene therapy in Alzheimer's disease - potential for disease modification.

    Science.gov (United States)

    Nilsson, Per; Iwata, Nobuhisa; Muramatsu, Shin-ichi; Tjernberg, Lars O; Winblad, Bengt; Saido, Takaomi C

    2010-04-01

    Alzheimer's disease (AD) is the major cause of dementia in the elderly, leading to memory loss and cognitive decline. The mechanism underlying onset of the disease has not been fully elucidated. However, characteristic pathological manifestations include extracellular accumulation and aggregation of the amyloid beta-peptide (Abeta) into plaques and intracellular accumulation and aggregation of hyperphosphorylated tau, forming neurofibrillary tangles. Despite extensive research worldwide, no disease modifying treatment is yet available. In this review, we focus on gene therapy as a potential treatment for AD, and summarize recent work in the field, ranging from proof-of-concept studies in animal models to clinical trials. The multifactorial causes of AD offer a variety of possible targets for gene therapy, including two neurotrophic growth factors, nerve growth factor and brain-derived neurotrophic factor, Abeta-degrading enzymes, such as neprilysin, endothelin-converting enzyme and cathepsin B, and AD associated apolipoprotein E. This review also discusses advantages and drawbacks of various rapidly developing virus-mediated gene delivery techniques for gene therapy. Finally, approaches aiming at down-regulating amyloid precursor protein (APP) and beta-site APP cleaving enzyme 1 levels by means of siRNA-mediated knockdown are briefly summarized. Overall, the prospects appear hopeful that gene therapy has the potential to be a disease modifying treatment for AD.

  17. 2014 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2014-03-01

    This report discusses the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, costs of care, and overall effect on caregivers and society. It also examines the impact of AD on women compared with men. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million are age 65 years or older. By mid-century, fueled in large part by the baby boom generation, the number of people living with AD in the United States is projected to grow by about 9 million. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. In 2010, official death certificates recorded 83,494 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans aged 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2014, an estimated 700,000 older Americans will die with AD, and many of them will die from complications caused by AD. In 2013, more than 15 million family members and other unpaid caregivers provided an estimated 17.7 billion hours of care to people with AD and other dementias, a contribution valued at more than $220 billion. Average per-person Medicare payments for services to beneficiaries aged 65 years and older with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as

  18. [Alzheimer's disease: a public health problem: yes, but a priority?].

    Science.gov (United States)

    Dartigues, J F; Helmer, C; Dubois, B; Duyckaerts, C; Laurent, B; Pasquier, F; Touchon, J

    2002-03-01

    Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

  19. How close is the stem cell cure to the Alzheimer's disease Future and beyond?

    Institute of Scientific and Technical Information of China (English)

    Jun Tang

    2012-01-01

    Alzheimer's disease, a progressive neurodegenerative illness, is the most common form of dementia. So far, there is neither an effective prevention nor a cure for Alzheimer's disease. In recent decades, stem cell therapy has been one of the most promising treatments for Alzheimer's disease patients. This article aims to summarize the current progress in the stem cell treatments for Alzheimer's disease from an experiment to a clinical research.

  20. Predicting missing biomarker data in a longitudinal study of Alzheimer disease

    Science.gov (United States)

    Jagust, William J.; Aisen, Paul; Jack, Clifford R.; Toga, Arthur W.; Beckett, Laurel; Gamst, Anthony; Soares, Holly; C. Green, Robert; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Chen, Kewei; Morris, John; Lee, Virginia M.-Y.; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Harvey, Danielle; Kornak, John; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Buckholtz, Neil; Kaye, Jeffrey; Dolen, Sara; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Tang, Cheuk; Marzloff, George; Toledo-Morrell, Leylade; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given, Curtis A.; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Brand, Connie; Richard, Jennifer; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Graff-Radford MBBCH, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Benincasa, Amanda L.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Wu, Chuang-Kuo; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Scott; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Jacobson, Sandra; Killiany, Ronald; Norbash, Alexander; Nair, Anil; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Englert, Jessica; Williamson, Jeff D.; Sink, Kaycee M.; Watkins, Franklin; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo

    2012-01-01

    Objective: To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). Methods: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. Results: CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. Conclusion: The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD. PMID:22491869

  1. Inherent Structure-Based Multiview Learning With Multitemplate Feature Representation for Alzheimer's Disease Diagnosis.

    Science.gov (United States)

    Liu, Mingxia; Zhang, Daoqiang; Adeli, Ehsan; Shen, Dinggang

    2016-07-01

    Multitemplate-based brain morphometric pattern analysis using magnetic resonance imaging has been recently proposed for automatic diagnosis of Alzheimer's disease (AD) and its prodromal stage (i.e., mild cognitive impairment or MCI). In such methods, multiview morphological patterns generated from multiple templates are used as feature representation for brain images. However, existing multitemplate-based methods often simply assume that each class is represented by a specific type of data distribution (i.e., a single cluster), while in reality, the underlying data distribution is actually not preknown. In this paper, we propose an inherent structure-based multiview leaning method using multiple templates for AD/MCI classification. Specifically, we first extract multiview feature representations for subjects using multiple selected templates and then cluster subjects within a specific class into several subclasses (i.e., clusters) in each view space. Then, we encode those subclasses with unique codes by considering both their original class information and their own distribution information, followed by a multitask feature selection model. Finally, we learn an ensemble of view-specific support vector machine classifiers based on their, respectively, selected features in each view and fuse their results to draw the final decision. Experimental results on the Alzheimer's Disease Neuroimaging Initiative database demonstrate that our method achieves promising results for AD/MCI classification, compared to the state-of-the-art multitemplate-based methods.

  2. Multi-method analysis of MRI images in early diagnostics of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Robin Wolz

    Full Text Available The role of structural brain magnetic resonance imaging (MRI is becoming more and more emphasized in the early diagnostics of Alzheimer's disease (AD. This study aimed to assess the improvement in classification accuracy that can be achieved by combining features from different structural MRI analysis techniques. Automatically estimated MR features used are hippocampal volume, tensor-based morphometry, cortical thickness and a novel technique based on manifold learning. Baseline MRIs acquired from all 834 subjects (231 healthy controls (HC, 238 stable mild cognitive impairment (S-MCI, 167 MCI to AD progressors (P-MCI, 198 AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI database were used for evaluation. We compared the classification accuracy achieved with linear discriminant analysis (LDA and support vector machines (SVM. The best results achieved with individual features are 90% sensitivity and 84% specificity (HC/AD classification, 64%/66% (S-MCI/P-MCI and 82%/76% (HC/P-MCI with the LDA classifier. The combination of all features improved these results to 93% sensitivity and 85% specificity (HC/AD, 67%/69% (S-MCI/P-MCI and 86%/82% (HC/P-MCI. Compared with previously published results in the ADNI database using individual MR-based features, the presented results show that a comprehensive analysis of MRI images combining multiple features improves classification accuracy and predictive power in detecting early AD. The most stable and reliable classification was achieved when combining all available features.

  3. Alzheimer's disease risk assessment using large-scale machine learning methods.

    Directory of Open Access Journals (Sweden)

    Ramon Casanova

    Full Text Available The goal of this work is to introduce new metrics to assess risk of Alzheimer's disease (AD which we call AD Pattern Similarity (AD-PS scores. These metrics are the conditional probabilities modeled by large-scale regularized logistic regression. The AD-PS scores derived from structural MRI and cognitive test data were tested across different situations using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI study. The scores were computed across groups of participants stratified by cognitive status, age and functional status. Cox proportional hazards regression was used to evaluate associations with the distribution of conversion times from mild cognitive impairment to AD. The performances of classifiers developed using data from different types of brain tissue were systematically characterized across cognitive status groups. We also explored the performance of anatomical and cognitive-anatomical composite scores generated by combining the outputs of classifiers developed using different types of data. In addition, we provide the AD-PS scores performance relative to other metrics used in the field including the Spatial Pattern of Abnormalities for Recognition of Early AD (SPARE-AD index and total hippocampal volume for the variables examined.

  4. Relationship Induced Multi-Template Learning for Diagnosis of Alzheimer's Disease and Mild Cognitive Impairment.

    Science.gov (United States)

    Liu, Mingxia; Zhang, Daoqiang; Shen, Dinggang

    2016-06-01

    As shown in the literature, methods based on multiple templates usually achieve better performance, compared with those using only a single template for processing medical images. However, most existing multi-template based methods simply average or concatenate multiple sets of features extracted from different templates, which potentially ignores important structural information contained in the multi-template data. Accordingly, in this paper, we propose a novel relationship induced multi-template learning method for automatic diagnosis of Alzheimer's disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI), by explicitly modeling structural information in the multi-template data. Specifically, we first nonlinearly register each brain's magnetic resonance (MR) image separately onto multiple pre-selected templates, and then extract multiple sets of features for this MR image. Next, we develop a novel feature selection algorithm by introducing two regularization terms to model the relationships among templates and among individual subjects. Using these selected features corresponding to multiple templates, we then construct multiple support vector machine (SVM) classifiers. Finally, an ensemble classification is used to combine outputs of all SVM classifiers, for achieving the final result. We evaluate our proposed method on 459 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 97 AD patients, 128 normal controls (NC), 117 progressive MCI (pMCI) patients, and 117 stable MCI (sMCI) patients. The experimental results demonstrate promising classification performance, compared with several state-of-the-art methods for multi-template based AD/MCI classification. PMID:26742127

  5. Inherent Structure-Based Multiview Learning With Multitemplate Feature Representation for Alzheimer's Disease Diagnosis.

    Science.gov (United States)

    Liu, Mingxia; Zhang, Daoqiang; Adeli, Ehsan; Shen, Dinggang

    2016-07-01

    Multitemplate-based brain morphometric pattern analysis using magnetic resonance imaging has been recently proposed for automatic diagnosis of Alzheimer's disease (AD) and its prodromal stage (i.e., mild cognitive impairment or MCI). In such methods, multiview morphological patterns generated from multiple templates are used as feature representation for brain images. However, existing multitemplate-based methods often simply assume that each class is represented by a specific type of data distribution (i.e., a single cluster), while in reality, the underlying data distribution is actually not preknown. In this paper, we propose an inherent structure-based multiview leaning method using multiple templates for AD/MCI classification. Specifically, we first extract multiview feature representations for subjects using multiple selected templates and then cluster subjects within a specific class into several subclasses (i.e., clusters) in each view space. Then, we encode those subclasses with unique codes by considering both their original class information and their own distribution information, followed by a multitask feature selection model. Finally, we learn an ensemble of view-specific support vector machine classifiers based on their, respectively, selected features in each view and fuse their results to draw the final decision. Experimental results on the Alzheimer's Disease Neuroimaging Initiative database demonstrate that our method achieves promising results for AD/MCI classification, compared to the state-of-the-art multitemplate-based methods. PMID:26540666

  6. Serum levels of S100B and NSE proteins in Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Souza Diogo O

    2010-01-01

    Full Text Available Abstract Background Alzheimer's disease is the most common dementia in the elderly, and the potential of peripheral biochemical markers as complementary tools in the neuropsychiatric evaluation of these patients has claimed further attention. Methods We evaluated serum levels of S100B and neuron-specific enolase (NSE in 54 mild, moderate and severe Alzheimer's disease (AD patients and in 66 community-dwelling elderly. AD patients met the probable NINCDS-ADRDA criteria. Severity of dementia was ascertained by the Clinical Dementia Rating (CDR scale, cognitive function by the Mini Mental State Examination (MMSE, and neuroimage findings with magnetic resonance imaging. Serum was obtained from all individuals and frozen at -70°C until analysis. Results By comparing both groups, serum S100B levels were lower in AD group, while serum NSE levels were the same both groups. In AD patients, S100B levels were positively correlated with CDR scores (rho = 0.269; p = 0.049 and negatively correlated with MMSE scores (rho = -0.33; P = 0.048. NSE levels decreased in AD patients with higher levels of brain atrophy. Conclusions The findings suggest that serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in AD.

  7. Hierarchical interactions model for predicting Mild Cognitive Impairment (MCI to Alzheimer's Disease (AD conversion.

    Directory of Open Access Journals (Sweden)

    Han Li

    Full Text Available Identifying patients with Mild Cognitive Impairment (MCI who are likely to convert to dementia has recently attracted increasing attention in Alzheimer's disease (AD research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features.

  8. Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in alzheimer's disease

    DEFF Research Database (Denmark)

    Zahn, R.; Garrard, P.; Talazko, J.;

    2006-01-01

    The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse da...... and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas.......The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse...... damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used...

  9. Deformability of Erythrocytes and Oxidative Damage in Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Mukerrem Betul Yerer

    2012-04-01

    Full Text Available Purpose: A lowered cerebral perfusion as a consequence of hemodynamic microcirculatory insufficiency is one of the factors underlying in Alzheimer's disease, which is a neurodegenerative disorder leading to progressive cognitive impairment. Erythrocyte deformability is one of the major factors affecting the microcirculatory hemodynamics which is closely related to the oxidative damage. The aim of this study is to investigate the relationship between the erythrocyte deformability, nitric oxide levels and oxidative stress in Alzheimer's disease. Methods: The blood samples of 30 elderly people in three groups consisting of healthy control and different severities of the disease (low and severe were used. Then the erythrocytes were isolated and the deformability of erythrocytes was determined by Rheodyne SSD evaluating the elongation indexes of the erythrocytes under different shear stress. The catalase, glutathione peroxidase and plasma nitric oxide levels were measured spectrophotometric ally. Results: The plasma nitric oxide levels, catalase activities were found significantly higher and glutathione peroxidase activity was significantly lower in severe Alzheimer's disease patients compared to the control group. However, the deformability of erythrocytes was not significantly affected from these alterations. Conclusion: the oxidant-antioxidant status is dramatically changed in Alzheimer's disease patients with the severity of the disease and similar alterations were seen in the nitric oxide levels without any significant change in erythrocyte deformability. [Cukurova Med J 2012; 37(2.000: 65-75

  10. 2013 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2013-03-01

    This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long-distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD-related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and

  11. Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Bhattacharya, Sumangala; Vogel, A.; Hansen, M.L.;

    2010-01-01

    The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD)....

  12. Parkinson's disease and Alzheimer's disease: hypersensitivity to X-rays in cultured cell lines

    International Nuclear Information System (INIS)

    Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death. (author)

  13. Therapeutics for Alzheimer's disease based on the metal hypothesis.

    Science.gov (United States)

    Bush, Ashley I; Tanzi, Rudolph E

    2008-07-01

    Alzheimer's disease is the most common form of dementia in the elderly, and it is characterized by elevated brain iron levels and accumulation of copper and zinc in cerebral beta-amyloid deposits (e.g., senile plaques). Both ionic zinc and copper are able to accelerate the aggregation of Abeta, the principle component of beta-amyloid deposits. Copper (and iron) can also promote the neurotoxic redox activity of Abeta and induce oxidative cross-linking of the peptide into stable oligomers. Recent reports have documented the release of Abeta together with ionic zinc and copper in cortical glutamatergic synapses after excitation. This, in turn, leads to the formation of Abeta oligomers, which, in turn, modulates long-term potentiation by controlling synaptic levels of the NMDA receptor. The excessive accumulation of Abeta oligomers in the synaptic cleft would then be predicted to adversely affect synaptic neurotransmission. Based on these findings, we have proposed the "Metal Hypothesis of Alzheimer's Disease," which stipulates that the neuropathogenic effects of Abeta in Alzheimer's disease are promoted by (and possibly even dependent on) Abeta-metal interactions. Increasingly sophisticated pharmaceutical approaches are now being implemented to attenuate abnormal Abeta-metal interactions without causing systemic disturbance of essential metals. Small molecules targeting Abeta-metal interactions (e.g., PBT2) are currently advancing through clinical trials and show increasing promise as disease-modifying agents for Alzheimer's disease based on the "metal hypothesis."

  14. Neuroimaging in assessment of risk of stroke in children with sickle cell disease

    International Nuclear Information System (INIS)

    Purpose: Stroke and subclinical '' silent infarcts '' are major causes of morbidity in children with Sickle Cell Disease (SCD). Ischemic strokes are more common in younger children while hemorrhagic strokes are more frequent in adults. The goal of neuroimaging in acute stroke is to document whether the stroke is ischemic or hemorrhagic, to assess the extent of parenchymal abnormalities and to determine the presence of other cerebrovascular lesions. Computed Tomography (CT) is the primary modality for the assessment of acute stroke patients because of its 24/7 availability and ability to exclude hemorrhagic causes. Magnetic resonance imaging (MRI) and MR angiography (MRA) are recommended to determine precisely extent of infarction and detect cerebrovascular abnormalities. The goal of neuroimaging in patients with hemorrhagic stroke is to identify an arteriovenous malformation or aneurysm(s) amenable to surgery or catheter intervention. The risk of first stroke is very high in asymptomatic children with intracranial arterial mean velocities over 200 cm/s on transcranial Doppler (TCD) examination. The risk can be substantially reduced if chronic blood transfusions are timely implemented. Large cerebral vessel disease detected by TCD can be confirmed or excluded by MRI/MRA. Those with evidence of parenchymal and/or cerebrovascular lesions should be followed by preventive therapy. In patients with neurologic symptoms and negative MRI/MRA findings Positron Emission Tomography or single photon emission CT is recommended. There are no specific neuroimaging findings that suggest that blood transfusions can be safely halted in children with SCD. (authors)

  15. Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Bhattacharya, Suvosree; Vogel, Asmus; Hansen, Marie-Louise H;

    2010-01-01

    The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD).......The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD)....

  16. Multiple testing for neuroimaging via hidden Markov random field.

    Science.gov (United States)

    Shu, Hai; Nan, Bin; Koeppe, Robert

    2015-09-01

    Traditional voxel-level multiple testing procedures in neuroimaging, mostly p-value based, often ignore the spatial correlations among neighboring voxels and thus suffer from substantial loss of power. We extend the local-significance-index based procedure originally developed for the hidden Markov chain models, which aims to minimize the false nondiscovery rate subject to a constraint on the false discovery rate, to three-dimensional neuroimaging data using a hidden Markov random field model. A generalized expectation-maximization algorithm for maximizing the penalized likelihood is proposed for estimating the model parameters. Extensive simulations show that the proposed approach is more powerful than conventional false discovery rate procedures. We apply the method to the comparison between mild cognitive impairment, a disease status with increased risk of developing Alzheimer's or another dementia, and normal controls in the FDG-PET imaging study of the Alzheimer's Disease Neuroimaging Initiative. PMID:26012881

  17. Emotional reactivity and awareness of task performance in Alzheimer's disease.

    Science.gov (United States)

    Mograbi, Daniel C; Brown, Richard G; Salas, Christian; Morris, Robin G

    2012-07-01

    Lack of awareness about performance in tasks is a common feature of Alzheimer's disease. Nevertheless, clinical anecdotes have suggested that patients may show emotional or behavioural responses to the experience of failure despite reporting limited awareness, an aspect which has been little explored experimentally. The current study investigated emotional reactions to success or failure in tasks despite unawareness of performance in Alzheimer's disease. For this purpose, novel computerised tasks which expose participants to systematic success or failure were used in a group of Alzheimer's disease patients (n=23) and age-matched controls (n=21). Two experiments, the first with reaction time tasks and the second with memory tasks, were carried out, and in each experiment two parallel tasks were used, one in a success condition and one in a failure condition. Awareness of performance was measured comparing participant estimations of performance with actual performance. Emotional reactivity was assessed with a self-report questionnaire and rating of filmed facial expressions. In both experiments the results indicated that, relative to controls, Alzheimer's disease patients exhibited impaired awareness of performance, but comparable differential reactivity to failure relative to success tasks, both in terms of self-report and facial expressions. This suggests that affective valence of failure experience is processed despite unawareness of task performance, which might indicate implicit processing of information in neural pathways bypassing awareness. PMID:22609573

  18. The Effect of Alzheimer's Disease and Aging on Conceptual Combination

    Science.gov (United States)

    Taler, Vanessa; Chertkow, Howard; Saumier, Daniel

    2005-01-01

    Alzheimer's disease (AD) subjects, healthy elderly, and young adults interpreted a series of novel noun-noun expressions composed of familiar object words. Subjects interpreted each item by selecting one of three possible definitions: a definition in which the referents of each noun were associated together in a particular context (e.g., rabbit…

  19. Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

    Directory of Open Access Journals (Sweden)

    Tobinick Edward L

    2008-01-01

    Full Text Available Abstract Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers. The efficacy of etanercept, a biologic antagonist of TNF-alpha, delivered by perispinal administration, for treatment of Alzheimer's disease over a period of six months has been previously reported in a pilot study. This report details rapid cognitive improvement, beginning within minutes, using this same anti-TNF treatment modality, in a patient with late-onset Alzheimer's disease. Rapid cognitive improvement following perispinal etanercept may be related to amelioration of the effects of excess TNF-alpha on synaptic mechanisms in Alzheimer's disease and provides a promising area for additional investigation and therapeutic intervention.

  20. Retrograde amnesia for semantic information in Alzheimer's disease

    NARCIS (Netherlands)

    Meeter, M.; Kollen, A.; Scheltens, P.

    2005-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde am

  1. Are Alzheimer's disease, hypertension, and cerebrocapillary damage related?

    NARCIS (Netherlands)

    Farkas, E; De Vos, RAI; Steur, ENHJ; Luiten, PGM

    2000-01-01

    Alzheimer's disease (AD) patients are often subject to vascular dysfunction besides their specific CNS pathology, which warrants further examination of the interaction between vascular factors and the development of dementia. The association of decreased cerebral blood flow (CBF) or hypertension wit

  2. Coping with Specific Stressors in Alzheimer's Disease Caregiving.

    Science.gov (United States)

    Williamson, Gail M.; Schulz, Richard

    1993-01-01

    Examined strategies used by 170 Alzheimer's disease caregivers to cope with memory deficits, communication impairments, and decline of loved one. Wishfulness was related to more depressed affect, regardless of stressor type. Relaxation in response to memory deficits, and acceptance in dealing with communication impairments and decline of loved one…

  3. Close encounter: mitochondria, endoplasmic reticulum and Alzheimer's disease

    OpenAIRE

    De Strooper, Bart; Scorrano, Luca

    2012-01-01

    Alzheimer's disease (AD) pathogenesis is linked to loss of presenilins, components of γ-secretase. Presenilins are located at MAM, a membrane domain at the interface of mitochondria and endoplasmic reticulum (ER). Presenilin loss alters ER–mitochondrial communication, linking it to AD pathogenesis.

  4. Neural activities during affective processing in people with Alzheimer's disease

    NARCIS (Netherlands)

    Lee, Tatia M. C.; Sun, Delin; Leung, Mei-Kei; Chu, Leung-Wing; Keysers, Christian

    2013-01-01

    This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to co

  5. Effects of music on autobiographical verbal narration in Alzheimer's disease

    NARCIS (Netherlands)

    El Haj, M.; Clement, S.; Fasotti, L.; Allain, P.

    2013-01-01

    There is a growing body of evidence suggesting a beneficial effect of music exposure on autobiographical memory in patients with Alzheimer's Disease (AD). Our paper was aimed at revealing the linguistic characteristics of these music-evoked autobiographical narrations. Eighteen AD patients and 18 he

  6. Roles of sigma-1 receptors in Alzheimer's disease.

    Science.gov (United States)

    Jin, Jia-Li; Fang, Min; Zhao, Yan-Xin; Liu, Xue-Yuan

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of senile dementia all over the world. Still no existing drugs can effectively reverse the cognitive impairment. However, Sigma-1 (σ-1) receptors have been long implicated in multiple neurological and psychiatric conditions over these years. In this review, we discuss the current understanding of σ-1 receptor functions. Through regulation of lipid rafts, secretases, kinases, neuroceptors and ion channels, σ-1 receptors can influence cellular signal transduction, TCA cycle, oxidative stress, neuron plasticity and neurotransmitter release etc. Based on this, we suggest the key cellular mechanisms linking σ-1 receptor to Alzheimer's disease. Besides, we detail the evidences showing that σ-1 receptors agonists, being the promising compounds for treatment of cognitive dysfunction, exhibit robust neuroprotection and anti-amnesia effect against Aβ neurotoxicity in the progress of Alzheimer's disease. The evidence comes from animal models, preclinical studies in humans and full clinical trials. In addition, the questions to be solved regarding this receptor are also presented. When concerned with NMDAR, σ-1 receptor activation may result in two totally different influences on AD. Utilization of σ-1 agents early in AD remains an overlooked therapeutic opportunity. This article may pave the way for further studies about sigma-1 receptor on Alzheimer's disease. PMID:26131055

  7. Neuropeptides in Alzheimer's Disease : From Pathophysiological Mechanisms to Therapeutic Opportunities

    NARCIS (Netherlands)

    Van Dam, Debby; Van Dijck, Annemie; Janssen, Leen; De Deyn, Peter Paul

    2013-01-01

    Neuropeptides are found throughout the entire nervous system where they can act as neurotransmitter, neuromodulator or neurohormone. In those functions, they play important roles in the regulation of cognition and behavior. In brain disorders like Alzheimer's disease (AD), where abnormal cognition a

  8. Semantic memory impairment in the earliest phases of Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Gade, Anders; Stokholm, Jette;

    2005-01-01

    The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD....

  9. The impact of Alzheimer's disease on the chinese economy

    DEFF Research Database (Denmark)

    Keogh-Brown, Marcus R; Jensen, Henning Tarp; Arrighi, H Michael;

    2016-01-01

    BACKGROUND: Recent increases in life expectancy may greatly expand future Alzheimer's Disease (AD) burdens. China's demographic profile, aging workforce and predicted increasing burden of AD-related care make its economy vulnerable to AD impacts. Previous economic estimates of AD predominantly...

  10. Music Enhances Autobiographical Memory in Mild Alzheimer's Disease

    Science.gov (United States)

    El Haj, Mohamad; Postal, Virginie; Allain, Philippe

    2012-01-01

    Studies have shown that the "Four Seasons" music may enhance the autobiographical performance of Alzheimer's disease (AD) patients. We used a repeated measures design in which autobiographical recall of 12 mild AD patients was assessed using a free narrative method under three conditions: (a) in "Silence," (b) after being exposed to the opus "Four…

  11. Semantic memory impairment in the earliest phases of Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Gade, Anders; Stokholm, Jette;

    2005-01-01

    The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD...

  12. Awareness of deficits in mild cognitive impairment and Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Stokholm, Jette; Gade, Anders;

    2004-01-01

    In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...

  13. Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

    DEFF Research Database (Denmark)

    Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga;

    2006-01-01

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD...

  14. Cost Analysis of Early Psychosocial Intervention in Alzheimer's Disease

    DEFF Research Database (Denmark)

    Søgaard, R.; Sørensen, J.; Waldorff, F.B.;

    2014-01-01

    BACKGROUND/AIM: To investigate the impact of early psychosocial intervention aimed at patients with Alzheimer's disease (AD) and their caregivers on resource use and costs from a societal perspective. METHODS: Dyads of patients and their primary caregiver were randomised to intervention (n = 163...

  15. Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Andreasen, Jesper Tobias; Arvaniti, Maria;

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus...

  16. Voice Onset Time Production in Speakers with Alzheimer's Disease

    Science.gov (United States)

    Baker, Julie; Ryalls, Jack; Brice, Alejandro; Whiteside, Janet

    2007-01-01

    In the present study, voice onset time (VOT) measurements were compared between a group of individuals with moderate Alzheimer's disease (AD) and a group of healthy age- and gender-matched peers. Participants read a list of consonant-vowel-consonant (CVC) words, which included the six stop consonants. The VOT measurements were made from…

  17. Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer's Disease

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Waldemar, Gunhild; Staehelin Jensen, Troels;

    2015-01-01

    BACKGROUND: Autonomic function has received little attention in Alzheimer's disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE: To investigate autonomic...

  18. Semantic Priming for Coordinate Distant Concepts in Alzheimer's Disease Patients

    Science.gov (United States)

    Perri, R.; Zannino, G. D.; Caltagirone, C.; Carlesimo, G. A.

    2011-01-01

    Semantic priming paradigms have been used to investigate semantic knowledge in patients with Alzheimer's disease (AD). While priming effects produced by prime-target pairs with associative relatedness reflect processes at both lexical and semantic levels, priming effects produced by words that are semantically related but not associated should…

  19. Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics.

    Science.gov (United States)

    Duce, James A; Bush, Ashley I

    2010-09-01

    The equilibrium of metal ions is critical for many physiological functions, particularly in the central nervous system, where metals are essential for development and maintenance of enzymatic activities, mitochondrial function, myelination, neurotransmission as well as learning and memory. Due to their importance, cells have evolved complex machinery for controlling metal-ion homeostasis. However, disruption of these mechanisms, or absorption of detrimental metals with no known biological function, alter the ionic balance and can result in a disease state, including several neurodegenerative disorders such as Alzheimer's disease. Understanding the complex structural and functional interactions of metal ions with the various intracellular and extracellular components of the central nervous system, under normal conditions and during neurodegeneration, is essential for the development of effective therapies. Accordingly, assisting the balance of metal ions back to homeostatic levels has been proposed as a disease-modifying therapeutic strategy for Alzheimer's disease as well as other neurodegenerative diseases.

  20. Pharmacological strategies for the prevention of Alzheimer's disease.

    Science.gov (United States)

    Doraiswamy, P Murali; Xiong, Glen L

    2006-01-01

    This review examines key pharmacological strategies that have been clinically studied for the primary or secondary prevention of Alzheimer's disease. Much information (neuropsychological, genetic and imaging) is already available to characterise an individual's risk for developing Alzheimer's disease. However, regulatory pathways for obtaining a prevention indication are less well charted, and such trials tend to involve 3- to 7-year studies of 1000 - 5000 individuals, depending on baseline status. Treatments developed for prevention will also need to have superior safety. For these reasons, > 100 proprietary pharmacological products are currently being developed for an Alzheimer's disease treatment, but only a few are being studied for prevention. Randomised trial data are available for antihypertensive agents (calcium channel blockers, angiotensin-converting enzyme inhibitors), pravastatin, simvastatin, conjugated oestrogen, raloxifene, rofecoxib, CX516 (AMPA agonist) and cholinesterase inhibitors regarding efficacy for Alzheimer's disease prevention. At least four large prevention trials of conjugated oestrogen, selenium and vitamin E, Ginkgo biloba and statins are currently underway. Strategies using other agents have not yet been evaluated in Alzheimer's disease prevention clinical trials. These include anti-amyloid antibodies, active immunisation, selective secretase inhibitors and modulators, microtubule stabilisers (e.g., paclitaxel), R-flurbiprofen, xaliproden, ONO-2506, FK962 (somatostatin releaser), SGS 742 (GABA(B) antagonist), TCH 346 (apoptosis inhibitor), Alzhemedtrade mark, phophodiesterase inhibitors, rosiglitazone, leuprolide, interferons, metal-protein attenuating compounds (e.g., PBT2), CX717, rasagaline, huperzine A, antioxidants and memantine. Studies combining lifestyle modification and drug therapy have not been conducted. Full validation of surrogate markers for disease progression (such as amyloid imaging) should further facilitate drug

  1. Alzheimer's Project

    Medline Plus

    Full Text Available ... disease has on those with Alzheimer's and their families. September 14, 2009 "The Alzheimer's Project" wins two ... way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on your Web site . ...

  2. Alzheimer's Myths

    Science.gov (United States)

    ... caused by another type of dementia . Myth 2: Alzheimer’s disease is not fatal. Reality: Alzheimer's disease has ... home. Myth 3: Only older people can get Alzheimer's Reality: Alzheimer's can strike people in their 30s, ...

  3. Regional fluorodeoxyglucose metabolism and instrumental activities of daily living across the Alzheimer's disease spectrum

    Science.gov (United States)

    Roy, Kamolika; Pepin, Lesley C.; Philiossaint, Marlie; Lorius, Natacha; Becker, J. Alex; Locascio, Joseph J.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad A.

    2014-01-01

    Background Impairment in instrumental activities of daily living (IADL) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Objective To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally. Methods One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cogniton, and behavior. Results The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time. Conclusion These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum. PMID:24898635

  4. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    Science.gov (United States)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  5. [Development of Disease-modifying Therapy for Alzheimer's Disease].

    Science.gov (United States)

    Akiyama, Haruhiko

    2016-04-01

    The development of disease-modifying therapy (DMT) that can arrest the pathological processes of Alzheimer's disease (AD) has emerged as one of the highest priorities of medical research. Two pathological hallmarks, amyloid-beta (Abeta) protein deposition and tau accumulation, are the major targets of DMT. Immunotherapy for Abeta removal and secretase inhibitors/modulators that reduce total or accumulation-prone Abeta are candidate DMTs against Abeta. Compounds that prevent tau aggregation are also under development. Clinical trials that test the efficacy of these DMT candidates are in preparation or ongoing. Recent studies of biomarkers of AD brain lesions have indicated that Abeta and tau accumulation appears 10 to 30 years before the occurrence of dementia and gradually propagate to reach the level that causes symptoms. Therefore, efficacy of DMT has to be evaluated in the preclinical stage of AD. The incidence of preclinical AD in the cognitively normal, aged population are estimated to be around 19%. Thus, currently available biomarkers, amyloid/tau PET imaging and cerebrospinal fluid measurements of Abeta and tau, are, perhaps, too invasive and costly. An international collaborative effort is needed to overcome this issue. PMID:27056864

  6. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

    Science.gov (United States)

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J.

    2016-01-01

    We examined the brains of 266 patients with prion diseases (PrionD) and found that 46 (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (Hu BrnAggs) to brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease (CJD) and found that the neurons in the Hu BrnAggs produced many β-amyloid (β42) inclusions, whereas uninfected, control-exposed Hu BrnAggs did not. Western blots of 20-pooled CJD-infected BrnAggs verified higher Aβ42 levels than controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many Aβ42 intraneuronal inclusions, low APOE-4, and no significant nerve cell loss. Seven patients had high levels of PrPSc, low Aβ42, high APOE-4 and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls and 2 controls had a few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to AD and suggest that PrionD are diseases of PrPSc, Aβ42, APOE-4 and abnormal tau. PMID:26226132

  7. Translocator protein (TSPO) role in aging and Alzheimer's disease.

    Science.gov (United States)

    Repalli, Jayanthi

    2014-01-01

    Cellular damage and deregulated apoptotic cell death lead to functional impairment, and a main consequence of these events is aging. Cellular damage is initiated by different stress/risk factors such as oxidative stress, inflammation, and heavy metals. These stress/risk factors affect the cellular homeostasis by altering methylation status of several aging and Alzheimer's disease associated genes; these effects can be manifested immediately after exposure to stress and at later stages of life. However, when cellular damage exceeds certain threshold levels apoptosis is initiated. This review discusses the stress factors involved in cellular damage and the role and potential of TSPO-mediated cell death in aging as well as in Alzheimer's disease, which is also characterized by extensive cell death. Mitochondrial-mediated apoptotic death through the release of cytochrome c is regulated by TSPO, and increased expression of this protein is observed in both elderly people and in patients with Alzheimer's disease. TSPO forms and mediates opening of the mitochondrial membrane pore, mPTP and oxidizes cardiolipin, and these events lead to the leakage of apoptotic death mediators, such as cytochrome c, resulting in cell death. However, TSPO has many proposed functions and can also increase steroid synthesis, which leads to inhibition of inflammation and inhibition of the release of apoptotic factors, thereby decreasing cell damage and promoting cell survival. Thus, TSPO mediates apoptosis and decreases the cell damage, which in turn dictates the process of aging as well as the functionality of organs such as the brain. TSPO modulation with ligands in the Alzheimer's disease mouse model showed improvement in behavioral symptoms, and studies in Drosophila species showed increased cell survival and prolonged lifespan in flies after TSPO inhibition. These data suggest that since effects/signs of stress can manifest at any time, prevention through change in lifestyle and TSPO

  8. Systematic review of atorvastatin for the treatment of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yuan Sun; Genfa Wang; Zhihong Pan; Shuyan Chen

    2012-01-01

    OBJECTIVE: To assess the clinical efficacy and safety of atorvastatin in the treatment of Alz-heimer's disease.DATA SOURCES: Medline (1948/2011-04), Embase (1966/2011-04), Cochrane Library (Issue 3, 2011), Chinese National Knowledge Infrastructure (1989/2011-04), and the Chinese Biomedical Literature Database (1979/2011-04) were searched for randomized clinical trials regardless of lan-guage. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org) were also searched.Key words included Alzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryl-CoA reductase inhibitors, atorvastatin and statins.DATA SELECTION: Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer's disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Revman 5.1 software was used for data analysis.MAIN OUTCOME MEASURES: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects.CONCLUSION: There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer's disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer's disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.

  9. Neuroprotective Effect against Alzheimer's Disease of Porcine Brain Extract

    Directory of Open Access Journals (Sweden)

    Wipawee Thukham-Mee

    2012-01-01

    Full Text Available Problem statement: Despite the increasing importance of Alzheimer’s disease, no effective therapeutic strategy is available. Therefore, neuroprotective strategy is still required. Recent findings show that numerous substances possessing antioxidant can improve neurodegeneration and memory impairment. Based on the antioxidant effect and its reputation to serve as brain tonic in traditional folklore, we hypothesized that porcine brain extract could mitigate neurodegeneration and memory impairment. Therefore, this study was set up to determine the effect of porcine brain extract on memory impairment and neurodegeneration in animal models of Alzheimer’s disease. Approach: Male Wistar rats (180-220 g had been orally given porcine brain extract at doses of 0.5 and 2.5 mg kg-1 BW for a period of 4 weeks before and 1 week after the induction of cognitive deficit condition as those found in early phase of Alzheimer’s disease via the intraventricular injection of AF64A, a cholinotoxin. Rats were assessed the spatial memory using Morris water maze test. Then, they were determined neuron density in hippocampus using histological techniques. Moreover, the assessment of acetylcholinesterase (AChE activity and malondialdehyde (MDA level in hippocampus were also performed. Results: It was found that both doses of porcine brain extract could enhance memory, neuron and cholinergic neuron density in all subregions of hippocampus. In addition, the decreased AChE and MDA were also observed. Therefore, our results suggested that the possible underlying mechanism of the extract might occur partly via the decrease in oxidative stress marker, MDA and AChE. Conclusion: This study clearly demonstrates that porcine brain extract can protect against memory impairment and neurodegeneration in animal model of Alzheimer’s disease. Therefore, it should be serve as the potential food supplement or adjuvant therapy against Alzheimer’s disease and other age-related cognitive

  10. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    Science.gov (United States)

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    -negative cases whose post-positon emission tomography diagnosis remained Alzheimer's disease. While the non-amnestic and non-specific amyloid-negative cases usually showed patterns of atrophy and hypometabolism suggestive of another degenerative disorder, the amnestic amyloid-negative cases had subtle atrophy and hypometabolism, restricted to the retrosplenial/posterior cingulate cortex. Patients with a negative amyloid positon emission tomography scan following an initial clinical diagnosis of Alzheimer's disease have heterogeneous clinical presentations and neuroimaging profiles; a majority showed a clinical progression that was consistent with a neurodegenerative condition. In contrast, in the subgroup of amnestic amyloid-negative cases, the clinical presentation and follow-up usually remained consistent with Alzheimer's disease. An alternative diagnosis was not made in about half of the amnestic amyloid-negative cases, highlighting the need for a clinical framework and terminology to define these patients, who may have underlying limbic-predominant, non-amyloid-related pathologies. PMID:27357349

  11. Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: A critical review.

    Science.gov (United States)

    Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Saini, Jitender; Pal, Pramod Kumar

    2015-07-01

    Patients with Parkinson's disease (PD) may develop various non-motor symptoms (NMS) during the course of the illness and psychosis is one of the common NMS of PD. Visual hallucinations (VH) are the most common manifestation of psychosis in PD. The exact pathogenesis of VH in patients with PD is not clearly understood. Presence of VH has been described to be associated with rapid cognitive decline and increased nursing home placements in PD patients. A large number of structural and functional neuroimaging studies have been conducted to understand the cerebral basis of VH in PD. Structural imaging studies (Voxel Based Morphometry) have reported grey matter atrophy in multiple regions of the brain such as primary visual cortex, visual association cortex, limbic regions, cholinergic structures such as pedunculopontine nucleus and substantia innominata, which conclude possible alterations of brain regions associated with functions such as visuospatial-perception, attention control and memory. Most functional neuroimaging studies (functional MRI, positron emission tomography and single photon emission computerized tomography) have reported altered activation, blood flow, or reduced metabolism in both dorsal and ventral visual pathways, which probably indicates an alteration in the normal bottom-top visual processing and the presence of an aberrant top-down visual processing. This review critically analyzes the published studies on the structural and functional neuroimaging in PD patients with VH.

  12. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD, the focus is the amyloid beta peptide (Aß that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

  13. Mortality from Alzheimer's Disease in the United States: Data for 2000 and 2010

    Science.gov (United States)

    ... System . Multiple cause-of-death files. Alzheimer's Association. Alzheimer's disease facts and figures, Alzheimer's & dementia [PDF - 1.2 MB] Vol 8, Issue 2. 2012. Hoyert DL, Xu JQ. Deaths: Preliminary data for 2011 [PDF - 891 KB] . ... Disease Education and Referral Center National Institute on Aging. ...

  14. Understanding suffering: Utermohlen's self-portraits and Alzheimer's disease.

    Science.gov (United States)

    Harrison, Elizabeth M

    2013-01-01

    Human suffering is a universal experience simply defined as, or associated with, physical or psychological pain and distress. Faculty seeks ways to help its students understand and ease their patients' suffering. The author uses Alzheimer's disease as an exemplar of suffering and describes a creative teaching strategy using 9 self-portraits that chronicle American-born artist William Utermohlen's deterioration from the disease. PMID:23222627

  15. Revisiting rodent models: Octodon degus as Alzheimer's disease model?

    Science.gov (United States)

    Steffen, Johannes; Krohn, Markus; Paarmann, Kristin; Schwitlick, Christina; Brüning, Thomas; Marreiros, Rita; Müller-Schiffmann, Andreas; Korth, Carsten; Braun, Katharina; Pahnke, Jens

    2016-01-01

    Alzheimer's disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these 'engineered' models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural 'sporadic Alzheimer's disease model' with 'Alzheimer's disease-like neuropathology'. To unveil advantages over the 'artificial' mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer's disease patients or transgenic disease models. PMID:27566602

  16. A Survey of TCM Treatment for Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Alzheimer's disease (AD) is a disorder in the aged people, characterized by irreversible and progressive degeneration of the intelligence, memory, ability of orientation, judgment, speech and thinking. It is often accompanied with character changes. Statistical data show that 5%-15% of the old people suffer from mild to severe symptoms of dementia, which becomes a burden to their families and the society. The following is a survey of TCM treatment for the disease.

  17. Vitamin D and the risk of dementia and Alzheimer disease

    OpenAIRE

    Thomas J Littlejohns; Henley, William E.; Lang, Iain A.; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H. M.; Fried, Linda; Kestenbaum, Bryan R.; Kuller, Lewis H.; Langa, Kenneth M.; Lopez, Oscar L.; Kos, Katarina; Soni, Maya; Llewellyn, David J.

    2014-01-01

    Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass...

  18. Chronic mild cerebrovascular dysfunction as a cause for Alzheimer's disease?

    OpenAIRE

    Humpel, Christian

    2011-01-01

    Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by β-amyloid plaques and angiopathy, tau pathology, neuronal cell death, and inflammatory responses. The reasons for this disease are not known. This review proposes the hypothesis that a chronic mild longlasting cerebrovascular dysfunction could initiate a cascade of events leading to AD. It is suggested that (vascular) risk factors (e.g. hypercholesterolemia, type 2 diabetes, hyperhomocysteinemia) causes either ...

  19. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  20. Research progress on animal models of Alzheimer's disease

    OpenAIRE

    Dong, Wen; Wang, Rong

    2015-01-01

    Alzheimer's disease (AD) is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  1. Friend or foe? Targeting microglia in Alzheimer's disease.

    Science.gov (United States)

    Dhib-Jalbut, Suhayl

    2016-10-01

    Inflammation is believed to be a component of a number of degenerative brain diseases including Alzheimer's disease. A recent article by Fu and colleagues (2016) demonstrated that the cytokine IL-33 can modulate microglia in an animal model of AD to become better scavengers of beta-amyloid and less pro-inflammatory. The findings have potential therapeutic implications for a number of brain conditions. PMID:27442003

  2. Frontal variant of Alzheimer's disease and typical Alzheimer's disease: a comparative study

    Directory of Open Access Journals (Sweden)

    Bernardino Fernández-Calvo

    2013-01-01

    Full Text Available Clinical heterogeneity is one of the characteristics of Alzheimer's disease (AD. Hence, the atypical frontal or dysexecutive presentation is becoming increasingly well-known, although the underlying factors are still unknown. In this study, the neuropsychological performance of two groups of patients with AD (frontal variant--ADfv--and typical--TAD were compared. The ADfv group (n = 13 was selected due to the existence of frontal hypoperfusion on a simple photon emission computer tomography (SPECT. The results revealed that the ADfv group displayed a severe dysexecutive disorder, more severe neuropsychiatric symptomatology (disinhibition and apathy, more functional impairment, and it generated a higher caregiver overload than the TAD group without frontal impairment (n = 47. Despite the facts that the ADfv group's performance was poorer in all the neuropsychological tests, significant group differences were only found in the processing speed and visuoconstruction tasks. Logistic regression analysis revealed that the processing speed and mental flexibility scores significantly predicted a diagnosis of ADfv. The existence of the grasp reflex, anosognosia, and the absence of apolipoprotein E epsilon 4 allele (APOE e4 were also more prevalent in the ADfv group. This group had a predominance of males and it was more likely to have a positive family history of AD. To conclude, the study suggests that ADfv represents a subtype of AD that seems to have different clinical, neuropsychological, and genetic characteristics from TAD.

  3. Doença de Alzheimer esporádica de início precoce Sporadic early onset Alzheimer´s disease

    Directory of Open Access Journals (Sweden)

    Annibal Truzzi

    2005-01-01

    Full Text Available A doença de Alzheimer (DA é a principal causa de demência. Um subgrupo de pacientes apresenta sua forma familiar ou precoce (Alzheimer's disease (AD is the main cause of dementia. A subgroup of patients has the familial or early-onset (<65 years form of AD, with rapid course and a dominant genetic transmission through many generations. We report a case of a patient without a positive familiar history for AD, who presented early memory problems and progressive functional and cognitive (speech, praxis, executive functions e viso-spatial habilities decline. Behavioural (imnsonia, psychomotor agitation and hypersexuality and psychological (depression symptoms of AD were noticed in different stages of the disease. Structural and functional neuroimaging techniques showed impairment of posterior cortical areas. Early onset AD can be confounded with psychiatric disorders especially when there is no familiar history for AD. The presenile impact on both patient and family is intense and treatment in the early stages is very important to reduce patient and caregivers' burden.

  4. Impaired awareness of deficits and neuropsychiatric symptoms in early Alzheimer's disease: the Danish Alzheimer Intervention Study (DAISY)

    DEFF Research Database (Denmark)

    Vogel, Asmus; Waldorff, Frans Boch; Waldemar, Gunhild

    2010-01-01

    Impaired awareness may be associated with increased neuropsychiatric symptoms in moderate to severe Alzheimer's disease, but relatively little is known about the association in early Alzheimer's disease. The aim of this study was to investigate if impaired awareness was associated with a higher...... frequency of neuropsychiatric symptoms in early Alzheimer's disease. In a Danish multicenter study, 321 patients with MMSE score > or =20 were evaluated. Patients with poor insight had significantly more neuropsychiatric symptoms than patients with full insight. When patients had increasing neuropsychiatric...

  5. Fluorescence tomography in a murine model of Alzheimer's disease

    Science.gov (United States)

    Raymond, Scott B.; Kumar, Anand T. N.; Dunn, Andrew K.; Boas, David A.; Bacskai, Brian J.

    2007-02-01

    Noninvasive molecular imaging of amyloid plaques in murine Alzheimer's disease models would accelerate drug development and basic Alzheimer's research. Amyloid plaques differ from traditional fluorescent targets in size and spatial distribution and therefore present a unique challenge for biomarker development and tomography. To study imaging feasibility and establish biomarker criteria, we developed a digital mouse head model from a 100 μm-resolution, digital, segmented mouse atlas1. The cortical region of the brain was filled with a spatially uniform distribution of plaques that had different fluorescent properties from the surrounding brain tissue, similar to current transgenic mouse models of Alzheimer's disease. Fluorescence was simulated with a Monte Carlo algorithm using different plaque densities, detection geometries, and background fluorescence. Our preliminary results demonstrated that shielding effects might require nonlinear reconstruction algorithms and that background fluorescence would seriously hinder quantitative burden estimation. The Monte Carlo based approach presented here offers a powerful way to study the feasibility of non-invasive imaging in murine Alzheimer's models and to optimize experimental conditions.

  6. A family living with Alzheimer's disease: The communicative challenges.

    Science.gov (United States)

    Jones, Danielle

    2015-09-01

    Alzheimer's disease irrevocably challenges a person's capacity to communicate with others. Earlier research on these challenges focused on the language disorders associated with the condition and situated language deficit solely in the limitations of a person's cognitive and semantic impairments. This research falls short of gaining insight into the actual interactional experiences of a person with Alzheimer's and their family. Drawing on a UK data set of 70 telephone calls recorded over a two-and-a-half year period (2006-2008) between one elderly woman with Alzheimer's disease, and her daughter and son-in-law, this paper explores the role which communication (and its degeneration) plays in family relationships. Investigating these interactions, using a conversation analytic approach, reveals that there are clearly communicative difficulties, but closer inspection suggests that they arise due to the contingencies that are generated by the other's contributions in the interaction. That being so, this paper marks a departure from the traditional focus on language level analysis and the assumption that deficits are intrinsic to the individual with Alzheimer's, and instead focuses on the collaborative communicative challenges that arise in the interaction itself and which have a profound impact on people's lives and relationships.

  7. A family living with Alzheimer's disease: The communicative challenges.

    Science.gov (United States)

    Jones, Danielle

    2015-09-01

    Alzheimer's disease irrevocably challenges a person's capacity to communicate with others. Earlier research on these challenges focused on the language disorders associated with the condition and situated language deficit solely in the limitations of a person's cognitive and semantic impairments. This research falls short of gaining insight into the actual interactional experiences of a person with Alzheimer's and their family. Drawing on a UK data set of 70 telephone calls recorded over a two-and-a-half year period (2006-2008) between one elderly woman with Alzheimer's disease, and her daughter and son-in-law, this paper explores the role which communication (and its degeneration) plays in family relationships. Investigating these interactions, using a conversation analytic approach, reveals that there are clearly communicative difficulties, but closer inspection suggests that they arise due to the contingencies that are generated by the other's contributions in the interaction. That being so, this paper marks a departure from the traditional focus on language level analysis and the assumption that deficits are intrinsic to the individual with Alzheimer's, and instead focuses on the collaborative communicative challenges that arise in the interaction itself and which have a profound impact on people's lives and relationships. PMID:24339113

  8. 100 Years of Alzheimer's disease (1906-2006).

    Science.gov (United States)

    Lage, José Manuel Martínez

    2006-01-01

    As we commemorate the first centennial since Alzheimer's disease (AD) was first diagnosed, this article casts back into the past while also looking to the future. It reflects on the life of Alois Alzheimer (1864-1915) and the scientific work he undertook in describing the disorder suffered by Auguste D. from age 51 to 56 and the neuropathological findings revealed by her brain, reminding us of the origin of the eponym. It highlights how, throughout the 1960's, the true importance of AD as the major cause of late life dementia ultimately came to light and narrates the evolution of the concepts related to AD throughout the years and its recognition as a major public health problem. Finally, the article pays homage to the work done by the Alzheimer's Association and the research undertaken at the Alzheimer's Disease Centres within the framework of the National Institute on Aging (NIA) Program, briefly discussing the long road travelled in the fight against AD in the past 25 years and the scientific odyssey that we trust will result in finding a cure. PMID:17004362

  9. Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer's disease.

    Science.gov (United States)

    de Haan, W; van der Flier, W M; Koene, T; Smits, L L; Scheltens, P; Stam, C J

    2012-02-15

    The relation between pathology and cognitive dysfunction in dementia is still poorly understood, although disturbed communication between different brain regions is almost certainly involved. In this study we combine magneto-encephalography (MEG) and network analysis to investigate the role of functional sub-networks (modules) in the brain with regard to cognitive failure in Alzheimer's disease. Whole-head resting-state (MEG) was performed in 18 Alzheimer patients (age 67 ± 9, 6 females, MMSE 23 ± 5) and 18 healthy controls (age 66 ± 9, 11 females, MMSE 29 ± 1). We constructed functional brain networks based on interregional synchronization measurements, and performed graph theoretical analysis with a focus on modular organization. The overall modular strength and the number of modules changed significantly in Alzheimer patients. The parietal cortex was the most highly connected network area, but showed the strongest intramodular losses. Nonetheless, weakening of intermodular connectivity was even more outspoken, and more strongly related to cognitive impairment. The results of this study demonstrate that particularly the loss of communication between different functional brain regions reflects cognitive decline in Alzheimer's disease. These findings imply the relevance of regarding dementia as a functional network disorder. PMID:22154957

  10. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    Directory of Open Access Journals (Sweden)

    Jürgen Götz

    2009-11-01

    Full Text Available In dementia research, animal models have become indispensable tools. They not only model aspects of the human condition, but also simulate processes that occur in humans and hence provide insight into how disease is initiated and propagated. The present review discusses two prominent human neurodegenerative disorders, Alzheimer's disease and frontotemporal dementia. It discusses what we would like to model in animals and highlights some of the more recent achievements using species as diverse as mice, fish, flies and worms. Advances in imaging and therapy are explored. We also discuss some anticipated new models and developments. These will reveal how key players in the pathogenesis of Alzheimer's disease and frontotemporal dementia, such as the peptide Aβ (amyloid β and the protein tau, cause neuronal dysfunction and eventually, neuronal demise. Understanding these processes fully will lead to early diagnosis and therapy.

  11. Magnetoencephalography as a Putative Biomarker for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Edward Zamrini

    2011-01-01

    Full Text Available Alzheimer's Disease (AD is the most common dementia in the elderly and is estimated to affect tens of millions of people worldwide. AD is believed to have a prodromal stage lasting ten or more years. While amyloid deposits, tau filaments, and loss of brain cells are characteristics of the disease, the loss of dendritic spines and of synapses predate such changes. Popular preclinical detection strategies mainly involve cerebrospinal fluid biomarkers, magnetic resonance imaging, metabolic PET scans, and amyloid imaging. One strategy missing from this list involves neurophysiological measures, which might be more sensitive to detect alterations in brain function. The Magnetoencephalography International Consortium of Alzheimer's Disease arose out of the need to advance the use of Magnetoencephalography (MEG, as a tool in AD and pre-AD research. This paper presents a framework for using MEG in dementia research, and for short-term research priorities.

  12. Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics.

    Science.gov (United States)

    Sala Frigerio, Carlo; De Strooper, Bart

    2016-07-01

    Ten years of remarkable progress in understanding the fundamental biochemistry of Alzheimer's disease have been followed by ten years of remarkable and increasing clinical insight into the natural progression of the disorder. The concept of a long, intermediary, prodromal phase between the first appearance of amyloid plaques and tangles and the manifestation of dementia is now well established. The major challenge for the next decade is to chart the many cellular processes that underlie this phase and link the biochemical alterations to the clinical manifestation of Alzheimer's disease. We discuss here how genetics, new cell culture systems, and improved animal models will fuel this work. We anticipate that the resulting novel insights will provide a basis for further drug development for this terrible disease. PMID:27050320

  13. New therapeutic strategy for Parkinson's and Alzheimer's disease.

    Science.gov (United States)

    Esposito, E; Cuzzocrea, S

    2010-01-01

    The development of potential neuroprotective therapies for neurodegenerative diseases (Parkinson's and Alzheimer's Disease) must be based on understanding their molecular and biochemical pathogenesis. Many potential pathways of neuronal cell death have been implicated in a mouse model of neurodegenerative disease, including excitotoxicity, toxicity from reactive oxygen species (superoxide anion, nitric oxide, hydroxyl radical), apoptosis (caspase-dependent and -independent pathways), necrosis and glial injury. Some agents that act on these pathways may be available for protecting the brain against chronic neurodegenerative conditions like Parkinson's and Alzheimer's disease. Drugs currently used to treat neurological disease and injuries provide temporary relief of symptoms but do not stop or slow the underlying neurodegenerative process. Restorative therapies for Parkinson's Disease are currently focused on cell replacement and administration of growth factors and small-molecule neurotrophic agents. The new experimental drugs, by contrast, target the common, underlying cause of destructive process of brain cell death. For example, p53 inhibitors attack a key protein involved in nerve cell death and represent a new strategy for preserving brain function following sudden injury or chronic disease. Analogues of pifithrin-alpha (PFT), which was shown in previous studies to inhibit p53, were designed, synthesized and tested to see whether they would work against cultured brain cells and animal models of neurodegenerative disease. Moreover, several agents based on the predominant anti-amyloid strategy, targeting amyloid-beta (Aβ) peptide, which aggregates in the plaques that are a hallmark of Alzheimer's disease, would affect disease progression. Researchers are already making great strides in developing a vaccine for this progressive brain disorder. Immunization could offer a way to blunt or even prevent the deadly, memory-robbing disease. Here we review many of

  14. Association between Cytokine production and disease severity in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Farahzad Jabbari Azad

    2014-12-01

    Full Text Available The role of transforming growth factor (TGF-β1, interferon (IFN-γ, interleukin (IL-2, IL-3, and IL-6 in the pathogenesis of Alzheimer's Disease (AD has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients' disease risk. 40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and gender-matched control group was recruited. The participants' cognitive performance was measured according to the Mini Mental State Examination (MMSE, the Global Deterioration Scale (GDS and Clinical Dementia Ratio (CDR. The levels of cytokines were measured in supernatants of lymphocytes culture, using assays of ELISA and atomic absorption. Higher levels of IL-6 and IFN-γ were found more in the altered T lymphocytes of the AD patients rather than in the control individuals. Furthermore, a marginal significant difference was found between the TGF-β levels of the two study groups. Regression analysis of CDR score and cytokines showed the inverse significant correlation between CDR score and IFN-γ levels. Furthermore, the relation between MMSE scores and IFN-γ was significant, meaning that by increasing MMSE score, IFN-γ level was significantly increased. This study suggests that the levels of IL-6 and IFN-γ are significantly increased in altered T lymphocytes of AD patients, as compared to those who are not inflicted with AD, and that they are related to the patient's age. Also, IFN-γ is related to the severity stage of the AD.

  15. Dual task and postural control in Alzheimer's and Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Larissa Pires de Andrade

    2014-03-01

    Full Text Available Patients with neurodegenerative diseases are required to use cognitive resources while maintaining postural control. The aim of this study was to investigate the effects of a frontal cognitive task on postural control in patients with Alzheimer, Parkinson and controls. Thirty-eight participants were instructed to stand upright on a force platform in two experimental conditions: single and dual task. Participants with Parkinson's disease presented an increase in the coefficient of variation greater than 100% in the dual task as compared to the single task for center of pressure (COP area and COP path. In addition, patients with Parkinson's and Alzheimer's disease had a higher number of errors during the execution of the cognitive task when compared to the group of elderly without neurodegenerative diseases. The motor cortex, which is engaged in postural control, does not seem to compete with frontal brain regions in the performance of the cognitive task. However, patients with Parkinson's and Alzheimer's disease presented worsened performance in cognitive task.

  16. Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.

    Science.gov (United States)

    Trojano, Luigi; Gainotti, Guido

    2016-04-21

    Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing. PMID:27104898

  17. Bioinformatics methods in drug repurposing for Alzheimer's disease.

    Science.gov (United States)

    Siavelis, John C; Bourdakou, Marilena M; Athanasiadis, Emmanouil I; Spyrou, George M; Nikita, Konstantina S

    2016-03-01

    Alarming epidemiological features of Alzheimer's disease impose curative treatment rather than symptomatic relief. Drug repurposing, that is reappraisal of a substance's indications against other diseases, offers time, cost and efficiency benefits in drug development, especially when in silico techniques are used. In this study, we have used gene signatures, where up- and down-regulated gene lists summarize a cell's gene expression perturbation from a drug or disease. To cope with the inherent biological and computational noise, we used an integrative approach on five disease-related microarray data sets of hippocampal origin with three different methods of evaluating differential gene expression and four drug repurposing tools. We found a list of 27 potential anti-Alzheimer agents that were additionally processed with regard to molecular similarity, pathway/ontology enrichment and network analysis. Protein kinase C, histone deacetylase, glycogen synthase kinase 3 and arginase inhibitors appear consistently in the resultant drug list and may exert their pharmacologic action in an epidermal growth factor receptor-mediated subpathway of Alzheimer's disease. PMID:26197808

  18. Studying infrared light therapy for treating Alzheimer's disease

    Science.gov (United States)

    Han, Mengmeng; Wang, Qiyan; Zeng, Yuhui; Meng, Qingqiang; Zhang, Jun; Wei, Xunbin

    2016-03-01

    Alzheimer's disease (AD) is an extensive neurodegenerative disease. It is generally believed that there are some connections between AD and amyloid protein plaques in the brain. AD is a chronic disease that usually starts slowly and gets worse over time. The typical symptoms are memory loss, language disorders, mood swings and behavioral issues. Gradual losses of somatic functions eventually lead patients to death. Currently, the main therapeutic method is pharmacotherapy, which may temporarily reduce symptoms, but has many side effects. No current treatment can reverse AD's deterioration. Infrared (IR) light therapy has been studied in a range of single and multiple irradiation protocols in previous studies and was found beneficial for neuropathology. In our research, we have verified the effect of infrared light on AD through Alzheimer's disease mouse model. This transgenic mouse model is made by co-injecting two vectors encoding mutant amyloid precursor protein (APP) and mutant presenilin-1 (PSEN1). We designed an experimental apparatus for treating mice, which primarily includes a therapeutic box and a LED array, which emits infrared light. After the treatment, we assessed the effects of infrared light by testing cognitive performance of the mice in Morris water maze. Our results show that infra-red therapy is able to improve cognitive performance in the mouse model. It might provide a novel and safe way to treat Alzheimer's disease.

  19. Physical activity benefits for Alzheimer's disease patients (A Review)

    OpenAIRE

    Pano, Genti

    2014-01-01

    Alzheimer's disease (AD) is a chronic and degenerative disease which is the main cause for dementia in older adults. It is well known that exercise can reduce the risk level for vascular risk factors, heart diseases (Blair et al., 1996), atherosclerosis (Lakka et al., 2001), stroke (Kurl et al., 2001) and diabetes (Seals et al., 1984; Houmard et al., 1996), diseases that can increase the risk for dementia and AD (Gustafson et al., 2003). Main objective of this study was to review the latest l...

  20. Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines.

    Science.gov (United States)

    Keene, C Dirk; Darvas, Martin; Kraemer, Brian; Liggitt, Denny; Sigurdson, Christina; Ladiges, Warren

    2016-01-01

    Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD), have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1) cerebrospinal fluid (CSF) AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2) structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG), and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3) cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines and standards

  1. Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines

    Science.gov (United States)

    Keene, C. Dirk; Darvas, Martin; Kraemer, Brian; Liggitt, Denny; Sigurdson, Christina; Ladiges, Warren

    2016-01-01

    Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD), have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1) cerebrospinal fluid (CSF) AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2) structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG), and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3) cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines and standards

  2. Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines

    Directory of Open Access Journals (Sweden)

    C. Dirk Keene

    2016-06-01

    Full Text Available Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD, have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1 cerebrospinal fluid (CSF AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2 structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG, and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3 cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines

  3. Apatia na doença de Alzheimer Apathy in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Antônio Lúcio Teixeira-Jr

    2006-09-01

    Full Text Available Apatia é a mais comum síndrome neuropsiquiátrica na doença de Alzheimer, afetando entre 30 e 60% dos pacientes. Pode ser definida como perda de motivação e se manifesta com alterações afetivas, cognitivas e comportamentais, determinando, respectivamente, redução da resposta emocional, perda de autocrítica e retração social. Nesse artigo, são apresentadas as características clínicas da síndrome apática e suas perspectivas terapêuticas. Conclui-se que há uma superposição considerável entre apatia e depressão na doença de Alzheimer, mas ambas as condições são consideradas síndromes independentes. Intervenções farmacológicas para apatia incluem psicoestimulantes, como o metilfenidato, agentes dopaminérgicos e inibidores de colinesterase; mas os resultados são controversos e não há tratamento estabelecido.Apathy is the most common neuropsychiatry syndrome in Alzheimer's disease affecting 30-60% of patients. It can be defined as a loss of motivation and manifests in affect, cognition and behavioral changes, determining blunted emotional response, lack of insight and social retraction, respectively. In this paper, the clinical features and the therapeutic perspectives of apathy are presented. There is considerable overlap between apathy and depression in Alzheimer's disease, but both are considered discrete syndromes. Pharmacological interventions for apathy include psychostimulants, such as methylphenidate, dopaminergic agents and cholinesterase inhibitors, but the results are controversial and there is no established treatment.

  4. New perspectives in the search for reliable biomarkers in Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Laura Moreno

    2015-03-01

    Full Text Available Background and Objectives: The search for accurate biomarkers in Alzheimer Disease (AD, on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient therapeutic strategies. A wide variety of potential biomarkers are has been identified by neuroimaging techniques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF or blood. Recently, a growing number of studies are focused on the discovery of reliable blood-based biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases. In this review, the latest challenges in the search for accurate biomarkers of AD is revised, in particular, an update in blood-based biomarkers is described in depth. Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72.

  5. Discrepancy between self- and proxy-rated pain in Alzheimer's disease: results from the danish Alzheimer intervention study

    DEFF Research Database (Denmark)

    Jensen-Dahm, C.; Vogel, A.; Waldorff, F.B.;

    2012-01-01

    OBJECTIVES: To investigate the prevalence of self- and proxy-reported pain in a cohort with Alzheimer's disease (AD) and to identify characteristics of individuals with AD reporting pain. DESIGN: Data were collected at the baseline visit of the Danish Alzheimer Intervention Study. SETTING......: Community. PARTICIPANTS: Three hundred twenty-one community-living individuals with AD (MMSE >/= 20) and their primary caregivers. MEASUREMENTS: Pain was assessed as part of the EuroQol EQ-5D (caregiver- and self-rated). The Cornell Scale for Depression in Dementia, Quality of Life in Alzheimer's Disease...

  6. Environment, epigenetics and neurodegeneration: Focus on nutrition in Alzheimer's disease.

    Science.gov (United States)

    Nicolia, Vincenzina; Lucarelli, Marco; Fuso, Andrea

    2015-08-01

    Many different environmental factors (nutrients, pollutants, chemicals, physical activity, lifestyle, physical and mental stress) can modulate epigenetic markers in the developing and adult organism. Epigenetics, in turn, can cause and is associated with several neurodegenerative and aging-dependent human diseases. Alzheimer's disease certainly represents one of the most relevant neurodegenerative disorders due to its incidence and its huge socio-economic impact. Therefore, it is easy to understand why recent literature focuses on the epigenetic modifications associated with Alzheimer's disease and other neurodegenerative disorders. One of the most intriguing and, at the same time, worrying evidence is that even "mild" environmental factors (such as behavioral or physical stress) as well as the under-threshold exposure to pollutants and chemicals, can be effective. Finally, even mild nutrients disequilibria can result in long-lasting and functional alterations of many epigenetic markers, although they don't have an immediate acute effect. Therefore, we will probably have to re-define the current risk threshold for many factors, molecules and stresses. Among the many different environmental factors affecting the epigenome, nutrition represents one of the most investigated fields; the reasons are probably that each person interacts with nutrients and that, in turn, nutrients can modulate at molecular level the epigenetic biochemical pathways. The role that nutrition can exert in modulating epigenetic modifications in Alzheimer's disease will be discussed with particular emphasis on the role of B vitamins and DNA methylation. PMID:25456841

  7. Olive Oil and its Potential Effects on Alzheimer's Disease

    Science.gov (United States)

    Antony, Shan; Zhang, G. P.

    Alzheimer's disease is a neuro-degenerative brain disease that is responsible for affecting the lives of hundreds of thousands of people every year. There has been no evidence to suggest a cure for the disease and the only existing treatments have very low rates of success in trial patients. This is largely due to the fact that the brain is one of the most undiscovered parts of the human body. Brain chemistry is highly complex and responds to its environment in random and radical ways. My research includes testing the reactionary outcomes of combining compounds of olive oil with the 20 basic amino acids. Regions around the world with olive oil based diets show a direct correlation to lower rates of Alzheimer's. Testing few compounds of olive oil with chemicals already found in the brain may yield to a better understanding as to why that is. I took the compounds tyrosol, hydroxytyrosol, and oleocanthal, and combined them with the 20 basic amino acids and calculated the total energy of the new molecule. The molecules produced with acceptably low energy values will be the center of further research. These molecules could lead to truly understanding olive oil's effect on the brain, and ultimately, the cure or prevention of Alzheimer's disease.

  8. Caloric restriction: beneficial effects on brain aging and Alzheimer's disease.

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Vandendriessche, Charysse; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer's disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies. In this review, we will discuss the mechanisms and effects of CR on aging and Alzheimer's disease. A potential alternative to CR as a lifestyle modification is the use of CR mimetics. These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. We discuss the effect of two of the most investigated mimetics, resveratrol and rapamycin, on aging and their potential as Alzheimer's disease therapeutics. However, additional research will be needed to determine the safety, efficacy, and usability of CR and its mimetics before a general recommendation can be proposed to implement them. PMID:27240590

  9. Alzheimer's Disease: Mechanism and Approach to Cell Therapy.

    Science.gov (United States)

    Amemori, Takashi; Jendelova, Pavla; Ruzicka, Jiri; Urdzikova, Lucia Machova; Sykova, Eva

    2015-11-04

    Alzheimer's disease (AD) is the most common form of dementia. The risk of AD increases with age. Although two of the main pathological features of AD, amyloid plaques and neurofibrillary tangles, were already recognized by Alois Alzheimer at the beginning of the 20th century, the pathogenesis of the disease remains unsettled. Therapeutic approaches targeting plaques or tangles have not yet resulted in satisfactory improvements in AD treatment. This may, in part, be due to early-onset and late-onset AD pathogenesis being underpinned by different mechanisms. Most animal models of AD are generated from gene mutations involved in early onset familial AD, accounting for only 1% of all cases, which may consequently complicate our understanding of AD mechanisms. In this article, the authors discuss the pathogenesis of AD according to the two main neuropathologies, including senescence-related mechanisms and possible treatments using stem cells, namely mesenchymal and neural stem cells.

  10. Differentiating Alzheimer disease-associated aggregates with small molecules.

    Science.gov (United States)

    Honson, Nicolette S; Johnson, Ronald L; Huang, Wenwei; Inglese, James; Austin, Christopher P; Kuret, Jeff

    2007-12-01

    Alzheimer disease is diagnosed postmortem by the density and spatial distribution of beta-amyloid plaques and tau-bearing neurofibrillary tangles. The major protein component of each lesion adopts cross-beta-sheet conformation capable of binding small molecules with submicromolar affinity. In many cases, however, Alzheimer pathology overlaps with Lewy body disease, characterized by the accumulation of a third cross-beta-sheet forming protein, alpha-synuclein. To determine the feasibility of distinguishing tau aggregates from beta-amyloid and alpha-synuclein aggregates with small molecule probes, a library containing 72,455 small molecules was screened for antagonists of tau-aggregate-mediated changes in Thioflavin S fluorescence, followed by secondary screens to distinguish the relative affinity for each substrate protein. Results showed that >10-fold binding selectivity among substrates could be achieved, with molecules selective for tau aggregates containing at least three aromatic or rigid moieties connected by two rotatable bonds.

  11. Challenges, solutions, and recommendations for Alzheimer's disease combination therapy.

    Science.gov (United States)

    Hendrix, James A; Bateman, Randall J; Brashear, H Robert; Duggan, Cynthia; Carrillo, Maria C; Bain, Lisa J; DeMattos, Ronald; Katz, Russell G; Ostrowitzki, Susanne; Siemers, Eric; Sperling, Reisa; Vitolo, Ottavio V

    2016-05-01

    Given the complex neuropathology Alzheimer's disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer's Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders. PMID:27017906

  12. Alzheimer's disease: rare variants with large effect sizes.

    Science.gov (United States)

    Del-Aguila, Jorge L; Koboldt, Daniel C; Black, Kathleen; Chasse, Rachel; Norton, Joanne; Wilson, Richard K; Cruchaga, Carlos

    2015-08-01

    Recent advances in sequencing technology and novel genotyping arrays (focused on low-frequency and coding variants) have made it possible to identify novel coding variants with large effect sizes and also novel genes (TREM2, PLD3, UNC5C, and AKAP9) associated with Alzheimer's disease (AD) risk. The major advantages of these studies over the classic genome-wide association studies (GWAS) include the identification of the functional variant and the gene-driven association. In addition to the large effect size, these studies make it possible to model these variants and genes using cell and animal systems. On the other hand, the underlying population-variability of these very low allele frequency variants poses a great challenge to replicating results. Studies that include very large datasets (>10,000 cases and controls) and combine sequencing and genotyping approaches will lead to the identification of novel genes for Alzheimer's disease. PMID:26311074

  13. High-resolution PET studies in Alzheimer's disease

    International Nuclear Information System (INIS)

    Forty-seven patients with probable dementia of the Alzheimer type (DAT) and 30 healthy age-matched controls were scanned using [18F]-2-fluoro-2-deoxy-D-glucose on a Scanditronix PC 1024-7B tomograph (inplane resolution = 6 mm, axial resolution = 10 mm). Patients and controls were scanned in the resting state with their eyes patched and ears occluded. The regional cerebral metabolic rates for glucose (rCMRglc) in most major neocortical and subcortical gray matter regions, and certain metabolic ratios (rCMRglc/ calcarine rCMRglc), quantitatively discriminated even the mildly demented patients from healthy controls. The association neocortices showed metabolic abnormalities that were more severe than those in the sensorimotor and calcarine regions. All demented groups showed significant neuropsychological disturbances when compared to healthy controls. These data demonstrated widespread metabolic disturbances, particularly in the association areas, relatively early in Alzheimer's disease, and more profound involvement with disease progression

  14. Implication of alpha1-antichymotrypsin polymorphism in familial Alzheimer's disease.

    Science.gov (United States)

    Nacmias, B; Marcon, G; Tedde, A; Forleo, P; Latorraca, S; Piacentini, S; Amaducci, L; Sorbi, S

    1998-03-13

    A common polymorphism in the alpha1-antichymotrypsin (ACT) gene has been shown to modify the Apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. Using the polymerase chain reaction, we analyzed the segregation of the ACT and ApoE polymorphisms in familial Alzheimer's disease (FAD) patients carrying mutations in Presenilin (PS) and APP genes and in both early onset (EO) and late onset (LO) FAD patients without known mutations. Our data suggest that ACT does not represent an additional risk factor for PS and APP mutated families. However, in LOFAD patients a high frequency of the combined ACT/AA and ApoE epsilon4/epsilon4 genotypes suggest that ACT may interact with ApoE and play a role in LOFAD. PMID:9572591

  15. Protein phosphatase 2A, a key player in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Rong LIU; Qing TIAN

    2009-01-01

    Protein phosphatase 2A (PP2A) is the pre-dominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer's disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neurofibrillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation underlie PP2A inactivation in AD. β-amyloid (Aβ) over-production, estrogen deficiency and impaired homocys-teine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer's disease.

  16. Neuroimaging studies of striatum in cognition Part II: Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Alexandru eHanganu

    2015-10-01

    Full Text Available In recent years a gradual shift in the definition of Parkinson’s disease (PD has been established, from a classical akinetic-rigid movement disorder to a multi-system neurodegenerative disease. While the pathophysiology of PD is complex and goes much beyond the nigro-striatal degeneration, the striatum has been shown to be responsible for many cognitive functions. Patients with PD develop impairments in multiple cognitive domains and the PD model is probably the most extensively studied regarding striatum dysfunction and its influence on cognition. Up to 40% of PD patients present cognitive impairment even in the early stages of disease development. Thus understanding the key patterns of striatum and connecting regions’ influence on cognition will help develop more specific approaches to alleviate cognitive impairment and slow down its decline. This review focuses on the contribution of neuroimaging studies in understanding how striatum impairment affects cognition in PD.

  17. Cognitive rehabilitation in a visual variant of Alzheimer's disease

    OpenAIRE

    Alves, Jorge; Rosana MAGALHÃES; Arantes, Mavilde; Cruz, Sara; Gonçalves, Óscar F.; Sampaio, Adriana

    2015-01-01

    Alzheimer's disease (AD) is commonly associated with marked memory deficits; however, nonamnestic variants have been consistently described as well. Posterior cortical atrophy (PCA) is a progressive degenerative condition in which posterior regions of the brain are predominantly affected, therefore resulting in a pattern of distinctive and marked visuospatial symptoms, such as apraxia, alexia, and spatial neglect. Despite the growing number of studies on cognitive and neural bases of the visu...

  18. Fear conditioning in frontotemporal lobar degeneration and Alzheimer's disease

    OpenAIRE

    Hoefer, M.; Allison, S. C.; Schauer, G. F.; Neuhaus, J M; Hall, J.; Dang, J. N.; Weiner, M.W.; Miller, B. L.; Rosen, H.J.

    2008-01-01

    Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia.We studied FC in controls (n = 25), Alzheimer's disease (n =25) a...

  19. Brain Tocopherols Related to Alzheimer Disease Neuropathology in Humans

    OpenAIRE

    Morris, Martha Clare; Schneider, Julie A.; LI Hong; Tangney, Christy C; Nag, Sukrit; Bennett, David A.; Honer, William G.; Barnes, Lisa

    2014-01-01

    Randomized trials of α-tocopherol supplements on cognitive decline are negative whereas studies of dietary tocopherols show benefit. We investigated these inconsistencies by analyzing the relations of α- and γ-tocopherol brain concentrations to Alzheimer disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adju...

  20. Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

    OpenAIRE

    Tobinick Edward L; Gross Hyman

    2008-01-01

    Abstract Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligo...

  1. Retrograde amnesia for semantic information in Alzheimer's disease

    OpenAIRE

    Meeter, M.; Kollen, A.; Scheltens, P

    2005-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde amnesia within semantic memory. No evidence for a gradient within this amnesia was found, although one was present on an autobiographic test of retrograde amnesia that had a wider time scale. Several...

  2. Awareness of deficits in mild cognitive impairment and Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Stokholm, Jette; Gade, Anders;

    2004-01-01

    In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...... heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected...

  3. Analysis of electroencephalograms in Alzheimer's disease patients with multiscale entropy

    OpenAIRE

    Escudero, J; Abasolo, D; Hornero, R.; Espino, P; M. Lopez

    2006-01-01

    The aim of this study was to analyse the electroencephalogram ( EEG) background activity of Alzheimer's disease ( AD) patients using multiscale entropy (MSE). MSE is a recently developed method that quantifies the regularity of a signal on different time scales. These time scales are inspected by means of several coarse-grained sequences formed from the analysed signals. We recorded the EEGs from 19 scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the MSE profile f...

  4. Functional neuroanatomy of auditory scene analysis in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Hannah L. Golden

    2015-01-01

    Full Text Available Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name are used to segregate auditory ‘foreground’ and ‘background’. Patients with typical amnestic Alzheimer's disease (n = 13 and age-matched healthy individuals (n = 17 underwent functional 3T-MRI using a sparse acquisition protocol with passive listening to auditory stimulus conditions comprising the participant's own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable analogues of these conditions. Name identification (conditions containing the participant's own name contrasted with spectrally rotated analogues produced extensive bilateral activation involving superior temporal cortex in both the AD and healthy control groups, with no significant differences between groups. Auditory object segregation (conditions with interleaved name sounds contrasted with superimposed name sounds produced activation of right posterior superior temporal cortex in both groups, again with no differences between groups. However, the cocktail party effect (interaction of own name identification with auditory object segregation processing produced activation of right supramarginal gyrus in the AD group that was significantly enhanced compared with the healthy control group. The findings delineate an altered functional neuroanatomical profile of auditory scene analysis in Alzheimer's disease that may constitute a novel computational signature of this neurodegenerative pathology.

  5. Functional neuroanatomy of auditory scene analysis in Alzheimer's disease.

    Science.gov (United States)

    Golden, Hannah L; Agustus, Jennifer L; Goll, Johanna C; Downey, Laura E; Mummery, Catherine J; Schott, Jonathan M; Crutch, Sebastian J; Warren, Jason D

    2015-01-01

    Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known 'cocktail party effect' as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory 'foreground' and 'background'. Patients with typical amnestic Alzheimer's disease (n = 13) and age-matched healthy individuals (n = 17) underwent functional 3T-MRI using a sparse acquisition protocol with passive listening to auditory stimulus conditions comprising the participant's own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable) analogues of these conditions. Name identification (conditions containing the participant's own name contrasted with spectrally rotated analogues) produced extensive bilateral activation involving superior temporal cortex in both the AD and healthy control groups, with no significant differences between groups. Auditory object segregation (conditions with interleaved name sounds contrasted with superimposed name sounds) produced activation of right posterior superior temporal cortex in both groups, again with no differences between groups. However, the cocktail party effect (interaction of own name identification with auditory object segregation processing) produced activation of right supramarginal gyrus in the AD group that was significantly enhanced compared with the healthy control group. The findings delineate an altered functional neuroanatomical profile of auditory scene analysis in Alzheimer's disease that may constitute a novel computational signature of this neurodegenerative pathology. PMID:26029629

  6. Functional neuroanatomy of spatial sound processing in Alzheimer's disease.

    OpenAIRE

    Golden, HL; Agustus, JL; Nicholas, JM; Schott, JM; Crutch, SJ; L. Mancini; Warren, JD

    2016-01-01

    Deficits of auditory scene analysis accompany Alzheimer's disease (AD). However, the functional neuroanatomy of spatial sound processing has not been defined in AD. We addressed this using a "sparse" fMRI virtual auditory spatial paradigm in 14 patients with typical AD in relation to 16 healthy age-matched individuals. Sound stimulus sequences discretely varied perceived spatial location and pitch of the sound source in a factorial design. AD was associated with loss of differentiated cortica...

  7. Neuritin can normalize neural deficits of Alzheimer's disease

    OpenAIRE

    An, K; Jung, J. H.; Jeong, A Y; Kim, H G; Jung, S. Y.; Lee, K.; Kim, H. J.; Kim, S-J; Jeong, T-Y; Son, Y.; Kim, H-S; Kim, J-H

    2014-01-01

    Reductions in hippocampal neurite complexity and synaptic plasticity are believed to contribute to the progressive impairment in episodic memory and the mild cognitive decline that occur particularly in the early stages of Alzheimer's disease (AD). Despite the functional and therapeutic importance for patients with AD, intervention to rescue or normalize dendritic elaboration and synaptic plasticity is scarcely provided. Here we show that overexpression of neuritin, an activity-dependent prot...

  8. Sleep and Alzheimer disease pathology—a bidirectional relationship

    OpenAIRE

    Ju, Yo-El S.; Lucey, Brendan P.; Holtzman, David M.

    2013-01-01

    Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep–wake cycle directly influences levels of Aβ in the brain. In experimental models, sleep deprivation increases the concentration of soluble Aβ and results in chronic accumulation of Aβ, whereas sleep extension has the opposite effe...

  9. PET studies in Alzheimer disease and other degenerative dementias

    International Nuclear Information System (INIS)

    Neurodegenerative disorders cause a variety of dementia including Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and Huntington's disease. PET scan is useful for early detection and differential diagnosis of theses dementing disorders. Also, it provides valuable information about clinico-anatomical correlation, allowing better understanding of function of brain. Here we discuss recent achievements PET studies regarding these dementing disorders. Future progress in PET technology, new tracers, and image analysis will play an important role in further clarifying the disease pathophysiology and brain functions

  10. Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.

    Science.gov (United States)

    Egorova, Polina; Popugaeva, Elena; Bezprozvanny, Ilya

    2015-04-01

    Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and Alzheimer's disease (AD) represent a huge scientific and medical question, but the molecular mechanisms of these diseases are still not clear. There is increasing evidence that neuronal calcium signaling is abnormal in many neurodegenerative disorders. Abnormal neuronal calcium release from the endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic dysfunction, and eventual cell death. Neuronal loss is observed in most cases of neurodegenerative diseases. Recent experimental evidence supporting the role of neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in this review.

  11. Deep sparse multi-task learning for feature selection in Alzheimer's disease diagnosis.

    Science.gov (United States)

    Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2016-06-01

    Recently, neuroimaging-based Alzheimer's disease (AD) or mild cognitive impairment (MCI) diagnosis has attracted researchers in the field, due to the increasing prevalence of the diseases. Unfortunately, the unfavorable high-dimensional nature of neuroimaging data, but a limited small number of samples available, makes it challenging to build a robust computer-aided diagnosis system. Machine learning techniques have been considered as a useful tool in this respect and, among various methods, sparse regression has shown its validity in the literature. However, to our best knowledge, the existing sparse regression methods mostly try to select features based on the optimal regression coefficients in one step. We argue that since the training feature vectors are composed of both informative and uninformative or less informative features, the resulting optimal regression coefficients are inevidently affected by the uninformative or less informative features. To this end, we first propose a novel deep architecture to recursively discard uninformative features by performing sparse multi-task learning in a hierarchical fashion. We further hypothesize that the optimal regression coefficients reflect the relative importance of features in representing the target response variables. In this regard, we use the optimal regression coefficients learned in one hierarchy as feature weighting factors in the following hierarchy, and formulate a weighted sparse multi-task learning method. Lastly, we also take into account the distributional characteristics of samples per class and use clustering-induced subclass label vectors as target response values in our sparse regression model. In our experiments on the ADNI cohort, we performed both binary and multi-class classification tasks in AD/MCI diagnosis and showed the superiority of the proposed method by comparing with the state-of-the-art methods. PMID:25993900

  12. Deep sparse multi-task learning for feature selection in Alzheimer's disease diagnosis.

    Science.gov (United States)

    Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2016-06-01

    Recently, neuroimaging-based Alzheimer's disease (AD) or mild cognitive impairment (MCI) diagnosis has attracted researchers in the field, due to the increasing prevalence of the diseases. Unfortunately, the unfavorable high-dimensional nature of neuroimaging data, but a limited small number of samples available, makes it challenging to build a robust computer-aided diagnosis system. Machine learning techniques have been considered as a useful tool in this respect and, among various methods, sparse regression has shown its validity in the literature. However, to our best knowledge, the existing sparse regression methods mostly try to select features based on the optimal regression coefficients in one step. We argue that since the training feature vectors are composed of both informative and uninformative or less informative features, the resulting optimal regression coefficients are inevidently affected by the uninformative or less informative features. To this end, we first propose a novel deep architecture to recursively discard uninformative features by performing sparse multi-task learning in a hierarchical fashion. We further hypothesize that the optimal regression coefficients reflect the relative importance of features in representing the target response variables. In this regard, we use the optimal regression coefficients learned in one hierarchy as feature weighting factors in the following hierarchy, and formulate a weighted sparse multi-task learning method. Lastly, we also take into account the distributional characteristics of samples per class and use clustering-induced subclass label vectors as target response values in our sparse regression model. In our experiments on the ADNI cohort, we performed both binary and multi-class classification tasks in AD/MCI diagnosis and showed the superiority of the proposed method by comparing with the state-of-the-art methods.

  13. Cerebral correlates of psychotic symptoms in Alzheimer's disease

    Science.gov (United States)

    Mega, M.; Lee, L.; Dinov, I.; Mishkin, F.; Toga, A.; Cummings, J.

    2000-01-01

    BACKGROUND—Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities.
OBJECTIVES—To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT).
METHODS—Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map.
RESULTS—The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group.
CONCLUSION—Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

 PMID:10896687

  14. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    Science.gov (United States)

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning.

  15. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    Science.gov (United States)

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning. PMID:18674439

  16. Inflammatory proteins in plasma are associated with severity of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Rufina Leung

    Full Text Available Markers of Alzheimer's disease (AD are being widely sought with a number of studies suggesting blood measures of inflammatory proteins as putative biomarkers. Here we report findings from a panel of 27 cytokines and related proteins in over 350 subjects with AD, subjects with Mild Cognitive Impairment (MCI and elderly normal controls where we also have measures of longitudinal change in cognition and baseline neuroimaging measures of atrophy. In this study, we identify five inflammatory proteins associated with evidence of atrophy on MR imaging data particularly in whole brain, ventricular and entorhinal cortex measures. In addition, we observed six analytes that showed significant change (over a period of one year in people with fast cognitive decline compared to those with intermediate and slow decline. One of these (IL-10 was also associated with brain atrophy in AD. In conclusion, IL-10 was associated with both clinical and imaging evidence of severity of disease and might therefore have potential to act as biomarker of disease progression.

  17. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.

    Science.gov (United States)

    Locascio, Joseph J; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y; Flaherty, Alice W; Schwarzschild, Michael A; Hayes, Michael T; Wills, Anne-Marie; Shivraj Sohur, U; Mejia, Nicte I; Selkoe, Dennis J; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. PMID:26220939

  18. Single photon emission computed tomography in the diagnosis of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hanyu, Haruo; Asano, Tetsuichi; Abe, Shin`e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru; Shindo, Hiroaki; Abe, Kimihiko [Tokyo Medical Coll. (Japan)

    1997-06-01

    Studies with single photon emission computed tomography (SPECT) have shown temporoparietal (TP) hypoperfusion in patients with Alzheimer`s disease (AD). We evaluated the utility of this findings in the diagnosis of AD. SPECT images with {sup 123}I-iodoamphetamine were analyzed qualitatively by a rater without knowledge of the subject`s clinical status. Sixty-seven of 302 consecutive patients were judged as having TP hypoperfusion by SPECT imaging. This perfusion pattern was observed in 44 of 51 patients with AD, in 5 with mixed dementia, 8 with cerebrovascular disease (including 5 with dementia), 4 with Parkinson`s disease (including 2 with dementia), 1 with normal pressure hydrocephalus, 1 with slowly progressive aphasia, 1 with progressive autonomic failure, 2 with age-associated memory impairment, and 1 with unclassified dementia. The sensitivity for AD was 86.3% (44 of 51 AD), and the specificity was 91.2% (229 of 251 non-AD). Next, we looked for differences in perfusion images between patients with AD and without AD. Some patients without AD had additional hypoperfusion beyond TP areas: deep gray matter hypoperfusion and diffuse frontal hypoperfusion, which could be used to differentiate them from the patients with AD. Others could not be distinguished from patients with AD by their perfusion pattern. Although patients with other cerebral disorders occasionally have TP hypoperfusion, this finding makes the diagnosis of AD very likely. (author)

  19. Heat Shock Protein 90 in Alzheimer's Disease

    OpenAIRE

    Jiang-Rong Ou; Meng-Shan Tan; An-Mu Xie; Jin-Tai Yu; Lan Tan

    2014-01-01

    Alzheimer’s disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aβ) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, an...

  20. Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Min Soo Byun

    Full Text Available We aimed to identify and characterize subtypes of Alzheimer's disease (AD exhibiting different patterns of regional brain atrophy on MRI using age- and gender-specific norms of regional brain volumes. AD subjects included in the Alzheimer's Disease Neuroimaging Initiative study were classified into subtypes based on standardized values (Z-scores of hippocampal and regional cortical volumes on MRI with reference to age- and gender-specific norms obtained from 222 cognitively normal (CN subjects. Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes. Whole-brain-level gray matter (GM atrophy pattern using voxel-based morphometry (VBM and cerebrospinal fluid (CSF biomarkers of the subtypes were also investigated. Of 163 AD subjects, 58.9% were classified as the "both impaired" subtype with the typical hippocampal and cortical atrophy pattern, whereas 41.1% were classified as the subtypes with atypical atrophy patterns: "hippocampal atrophy only" (19.0%, "cortical atrophy only" (11.7%, and "both spared" (10.4%. Voxel-based morphometric analysis demonstrated whole-brain-level differences in overall GM atrophy across the subtypes. These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-β 1-42 levels compared to CN. In conclusion, we identified four AD subtypes exhibiting heterogeneous atrophy patterns on MRI with different progression rates after controlling the effects of aging and gender on atrophy with normative information. CSF biomarker analysis suggests the presence of Aβ neuropathology irrespective of subtypes. Such heterogeneity of MRI-based neuronal injury biomarker and related heterogeneous progression patterns should be considered in clinical trials and practice with AD patients.

  1. Ensembles of Deep Learning Architectures for the Early Diagnosis of the Alzheimer's Disease.

    Science.gov (United States)

    Ortiz, Andrés; Munilla, Jorge; Górriz, Juan M; Ramírez, Javier

    2016-11-01

    Computer Aided Diagnosis (CAD) constitutes an important tool for the early diagnosis of Alzheimer's Disease (AD), which, in turn, allows the application of treatments that can be simpler and more likely to be effective. This paper explores the construction of classification methods based on deep learning architectures applied on brain regions defined by the Automated Anatomical Labeling (AAL). Gray Matter (GM) images from each brain area have been split into 3D patches according to the regions defined by the AAL atlas and these patches are used to train different deep belief networks. An ensemble of deep belief networks is then composed where the final prediction is determined by a voting scheme. Two deep learning based structures and four different voting schemes are implemented and compared, giving as a result a potent classification architecture where discriminative features are computed in an unsupervised fashion. The resulting method has been evaluated using a large dataset from the Alzheimer's disease Neuroimaging Initiative (ADNI). Classification results assessed by cross-validation prove that the proposed method is not only valid for differentiate between controls (NC) and AD images, but it also provides good performances when tested for the more challenging case of classifying Mild Cognitive Impairment (MCI) Subjects. In particular, the classification architecture provides accuracy values up to 0.90 and AUC of 0.95 for NC/AD classification, 0.84 and AUC of 0.91 for stable MCI/AD classification and 0.83 and AUC of 0.95 for NC/MCI converters classification.

  2. Regional cortical thinning and cerebrospinal biomarkers predict worsening daily functioning across the Alzheimer disease spectrum

    Science.gov (United States)

    Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2014-01-01

    Background Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p<0.0001), greater lateral occipital cortical thickness and diagnosis (p<0.0001), and greater amyloid-beta 1-42 (Aβ1-42) and diagnosis (p=0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p=0.02) and inferior temporal (p=0.05) cortical thickness, lower Aβ1-42 (p<0.0001), and greater total tau (t-tau) (p=0.02) were associated with greater rate of IADL impairment over time. Conclusions Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI. PMID:24685624

  3. Amyloid and APOE ε4 interact to influence short-term decline in preclinical Alzheimer disease

    Science.gov (United States)

    Betensky, Rebecca A.; Hedden, Trey; Schultz, Aaron P.; Ward, Andrew; Huijbers, Willem; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2014-01-01

    Objective: To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN). Methods: Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE ε4 and Aβ on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores). Results: High Aβ participants were more likely to be APOE ε4+ than low Aβ participants. CNs who were both high Aβ and APOE ε4+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low Aβ/APOE ε4−, low Aβ/APOE ε4+, and high Aβ/APOE ε4−). No other pairwise contrast was significant for any cognitive measure. Conclusions: Clinically normal individuals who are APOE ε4+ and have high Aβ showed the highest cognitive decline. These results suggest that Aβ and APOE ε4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging. PMID:24748674

  4. Risk classification in mild cognitive impairment patients for developing Alzheimer's disease.

    Science.gov (United States)

    Zhou, Bin; Nakatani, Eiji; Teramukai, Satoshi; Nagai, Yoji; Fukushima, Masanori

    2012-01-01

    The objective of this study was to develop new risk classifications for conversion to Alzheimer's disease (AD) by comparing the relative reliability of classifiers in patients with mild cognitive impairment (MCI). The 397 MCI subjects and all baseline data, including characteristics, neuropsychological tests, cerebrospinal fluid biomarkers and MRI findings in Alzheimer's Disease Neuroimaging Initiative (ADNI), were used for analysis by Cox proportional hazard regression, bootstrap sampling, and c-index. Multivariate Cox regression analysis revealed the following factors to be associated with increased risk of conversion from MCI to AD during the 53-month follow-up period: AVLT 30-minute delayed recall, AVLT trial 1, Boston naming, logical delayed recall, trail-making B, CDR-sob, ADAS13, the cortical thickness of the right inferior temporal lobe (st91ta), and the left hippocampus volume. The combinations of ADAS13 at a cutoff point of 15.67 with CDR-sob at 1.5 or with the cortical thickness of the right inferior temporal lobe at 2.56 mm3 produced high conversion rates of 92.7% (82.4%-100.0%) and 88.8% (77.3%-100.0%), respectively, at 48 months. The discriminative ability based on c-index for the proposed combination was 0.68. The sample size was estimated as 504 in the group with a combination of ADAS13 and CDR-sob whose conversion rate is highest. The combination of ADAS13 with CDR-sob at an optimal cutoff point has a high reliability in classifying the MCI patients into high- and low-risk conversion to AD and will be benefit for patients' assessment and potentially facilitate the clinical development of novel therapeutics. PMID:22426014

  5. Identification of conversion from mild cognitive impairment to Alzheimer's disease using multivariate predictors.

    Directory of Open Access Journals (Sweden)

    Yue Cui

    Full Text Available Prediction of conversion from mild cognitive impairment (MCI to Alzheimer's disease (AD is of major interest in AD research. A large number of potential predictors have been proposed, with most investigations tending to examine one or a set of related predictors. In this study, we simultaneously examined multiple features from different modalities of data, including structural magnetic resonance imaging (MRI morphometry, cerebrospinal fluid (CSF biomarkers and neuropsychological and functional measures (NMs, to explore an optimal set of predictors of conversion from MCI to AD in an Alzheimer's Disease Neuroimaging Initiative (ADNI cohort. After FreeSurfer-derived MRI feature extraction, CSF and NM feature collection, feature selection was employed to choose optimal subsets of features from each modality. Support vector machine (SVM classifiers were then trained on normal control (NC and AD participants. Testing was conducted on MCIc (MCI individuals who have converted to AD within 24 months and MCInc (MCI individuals who have not converted to AD within 24 months groups. Classification results demonstrated that NMs outperformed CSF and MRI features. The combination of selected NM, MRI and CSF features attained an accuracy of 67.13%, a sensitivity of 96.43%, a specificity of 48.28%, and an AUC (area under curve of 0.796. Analysis of the predictive values of MCIc who converted at different follow-up evaluations showed that the predictive values were significantly different between individuals who converted within 12 months and after 12 months. This study establishes meaningful multivariate predictors composed of selected NM, MRI and CSF measures which may be useful and practical for clinical diagnosis.

  6. Ensembles of Deep Learning Architectures for the Early Diagnosis of the Alzheimer's Disease.

    Science.gov (United States)

    Ortiz, Andrés; Munilla, Jorge; Górriz, Juan M; Ramírez, Javier

    2016-11-01

    Computer Aided Diagnosis (CAD) constitutes an important tool for the early diagnosis of Alzheimer's Disease (AD), which, in turn, allows the application of treatments that can be simpler and more likely to be effective. This paper explores the construction of classification methods based on deep learning architectures applied on brain regions defined by the Automated Anatomical Labeling (AAL). Gray Matter (GM) images from each brain area have been split into 3D patches according to the regions defined by the AAL atlas and these patches are used to train different deep belief networks. An ensemble of deep belief networks is then composed where the final prediction is determined by a voting scheme. Two deep learning based structures and four different voting schemes are implemented and compared, giving as a result a potent classification architecture where discriminative features are computed in an unsupervised fashion. The resulting method has been evaluated using a large dataset from the Alzheimer's disease Neuroimaging Initiative (ADNI). Classification results assessed by cross-validation prove that the proposed method is not only valid for differentiate between controls (NC) and AD images, but it also provides good performances when tested for the more challenging case of classifying Mild Cognitive Impairment (MCI) Subjects. In particular, the classification architecture provides accuracy values up to 0.90 and AUC of 0.95 for NC/AD classification, 0.84 and AUC of 0.91 for stable MCI/AD classification and 0.83 and AUC of 0.95 for NC/MCI converters classification. PMID:27478060

  7. Diffusion tensor metrics as biomarkers in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Julio Acosta-Cabronero

    Full Text Available BACKGROUND: Although diffusion tensor imaging has been a major research focus for Alzheimer's disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer's disease. METHODS: The biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics, and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N = 21 and mild (N = 22 Alzheimer's disease patients were examined as well as a longitudinal cohort (N = 16 that had been rescanned at 12 months. FINDINGS AND SIGNIFICANCE: The results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as 'state-specific' markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear 'stage-specific' and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the

  8. Beneficial effects of melatonin in experimental models of Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    Yong CHENG; Zheng FENG; Qing-zhu ZHANG; Jun-tian ZHANG

    2006-01-01

    Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss.Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxidant and free radical scavenger. Additionally, melatonin stimulates several antioxidative enzymes and improves mitochondrial energy metabolism. These findings led us to study amyloid precursor protein transgenic mice, ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe whether melatonin had any effect on Alzheimer's symptoms or pathological changes. We found that melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of β-amyloid (Aβ) deposition and Aβ fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation.These actions may potentially slow down or stop the progression of dementia.

  9. Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect

    KAUST Repository

    Demetrius, Lloyd A.

    2015-01-14

    Epidemiological and biochemical studies show that the sporadic forms of Alzheimer\\'s disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.

  10. Comparison of the cerebral SPECT and biological markers in the Alzheimer disease

    International Nuclear Information System (INIS)

    This study aim was to compare the contribution of SPECT of cerebral perfusion and bio markers of the cerebrospinal liquid in the diagnosis of Alzheimer disease. Our preliminary conclusions show that the concordance of the SPECT and cerebrospinal liquid is good in the possible Alzheimer disease. the interest of the cerebral SPECT and bio markers of the cerebrospinal liquid, used alone or conjointly, for a more reliable diagnosis of Alzheimer disease must be evaluated of prospective way. (N.C.)

  11. Alzheimer's disease care management plan: maximizing patient care.

    Science.gov (United States)

    Treinkman, Anna

    2005-03-01

    Nurse practitioners have the potential to significantly impact the care of patients with dementia. Healthcare providers can now offer patients medications that will control symptoms and prolong functioning. As a result of ongoing contact with patients, NPs play an important role in assessing and screening patients for AD and educating the patients, families, and caregivers about the disease. Alzheimer's disease is a chronic, progressive illness that requires long-term management. Nurse practitioners should be familiar with available medications and appreciate the need to individualize therapy to maximize efficacy and minimize potential adverse drug reactions.

  12. Does ionizing radiation influence Alzheimer's disease risk?

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is a human neurodegenerative disease, and its global prevalence is predicted to increase dramatically in the following decades. There is mounting evidence describing the effects of ionizing radiation (IR) on the brain, suggesting that exposure to IR might ultimately favor the development of AD. Therefore better understanding the possible connections between exposure to IR and AD pathogenesis is of utmost importance. In this review, recent developments in the research on the biological and cognitive effects of IR in the brain will be explored. Because AD is largely an age-related pathology, the effects of IR on ageing will be investigated

  13. Towards an All-Polymer Biosensor for Early Alzheimer's Disease

    OpenAIRE

    Christiansen, Nikolaj Ormstrup; Rozlosnik, Noemi; Heegaard, Niels

    2013-01-01

    Alzheimer's disease (AD) is quickly evolving into one of the biggest and most costly health issues in Europe and the United States. AD is a protein misfolding disease, caused by accumulation of abnormally folded β-amyloid and tau protein in the brain. The build-up of protein is believed to degenerate the brain tissue literally shrinking the brain. This slowly destroys function of these parts of the brain. It has been discovered that the concentration of A42 in cerebrospinal fluid (CSF) is a b...

  14. Numb and Alzheimer's Disease: The Current Picture.

    Directory of Open Access Journals (Sweden)

    Dimitrios eNtelios

    2012-10-01

    Full Text Available Twenty three years ago, numb was identified as a critical regulator in Drosophila sensory organ precursor cell asymmetric divisions. Beyond the recently recognized role in carcinogenesis, Numb seems to be important in Alzheimer’s disease. This assertion comes from the involvement in various processes such as synapse morphogenesis, APP trafficking, notch signaling and neurogenesis. The purpose of the present mini-review is to provide the current picture of Numb’s participation in mechanisms underlying Alzheimer’s disease pathogenesis and emphasize potential aspects for future research.

  15. Estado nutricional na doença de Alzheimer Nutritional status in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jacqueline Machado

    2009-01-01

    Full Text Available OBJETIVO: Descrever aspectos nutricionais de idosos com doença de Alzheimer leve a moderada em ambulatório. MÉTODOS: A amostra contou com a participação de 40 idosos de ambos os sexos, diagnosticados com doença da Alzheimer (NINCDS-ADRDA por seleção consecutiva. Foram realizadas avaliações socioeconômicas de atividades de vida diária, antropométrica, clínica e dietética. RESULTADOS: Do total, 65% eram do sexo feminino. Ao se verificar a capacidade funcional, constatou-se que mais de 70% dos idosos mostraram-se independentes para a realização de suas atividades de vida diária. Com base na avaliação do estado nutricional e na gravidade da doença, os idosos encontraram-se eutróficos, com diferença estatisticamente significativa na circunferência do braço entre os graus de demência. Quanto à presença de enfermidades secundárias à doença, 52% dos idosos apresentaram hipertensão arterial sistêmica, seguido de alterações do tipo artrose (17%. O consumo médio de energia e de macronutrientes dos idosos classificados no estágio leve foi de 1645 kcal, distribuídos em 53,7% para carboidratos, 17,5% para proteínas e 28,8% para lipídeos, enquanto que aqueles no estágio moderado foi de 1482 kcal, distribuídos em 59,3% para carboidratos, 16,1% para proteínas e 24,6% para lipídeos. CONCLUSÃO: Neste estudo descritivo de uma amostra ambulatorial de idosos com DA leve e moderada a maior parte deles apresentou estado nutricional de eutrofia, com consumo dietético adequado de carboidratos, proteínas, lipídeos e vitamina C, embora com baixo consumo alimentar de vitamina E.OBJECTIVE: To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. METHODS: Subjects of both genders (n=40 diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary

  16. Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families.

    Science.gov (United States)

    Cuenco, Karen T; Friedland, Robert; Baldwin, Clinton T; Guo, Jianping; Vardarajan, Badri; Lunetta, Kathryn L; Cupples, L Adrienne; Green, Robert C; DeCarli, Charles; Farrer, Lindsay A

    2011-02-01

    In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

  17. Nano-biosensors to detect beta-amyloid for Alzheimer's disease management.

    Science.gov (United States)

    Kaushik, Ajeet; Jayant, Rahul Dev; Tiwari, Sneham; Vashist, Arti; Nair, Madhavan

    2016-06-15

    Beta-amyloid (β-A) peptides are potential biomarkers to monitor Alzheimer's diseases (AD) for diagnostic purposes. Increased β-A level is neurotoxic and induces oxidative stress in brain resulting in neurodegeneration and causes dementia. As of now, no sensitive and inexpensive method is available for β-A detection under physiological and pathological conditions. Although, available methods such as neuroimaging, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) detect β-A, but they are not yet extended at point-of-care (POC) due to sophisticated equipments, need of high expertize, complicated operations, and challenge of low detection limit. Recently, β-A antibody based electrochemical immuno-sensing approach has been explored to detect β-A at pM levels within 30-40 min compared to 6-8h of ELISA test. The introduction of nano-enabling electrochemical sensing technology could enable rapid detection of β-A at POC and may facilitate fast personalized health care delivery. This review explores recent advancements in nano-enabling electrochemical β-A sensing technologies towards POC application to AD management. These analytical tools can serve as an analytical tool for AD management program to obtain bio-informatics needed to optimize therapeutics for neurodegenerative diseases diagnosis management.

  18. Classification of structural MRI images in Alzheimer's disease from the perspective of ill-posed problems.

    Directory of Open Access Journals (Sweden)

    Ramon Casanova

    Full Text Available BACKGROUND: Machine learning neuroimaging researchers have often relied on regularization techniques when classifying MRI images. Although these were originally introduced to deal with "ill-posed" problems it is rare to find studies that evaluate the ill-posedness of MRI image classification problems. In addition, to avoid the effects of the "curse of dimensionality" very often dimension reduction is applied to the data. METHODOLOGY: Baseline structural MRI data from cognitively normal and Alzheimer's disease (AD patients from the AD Neuroimaging Initiative database were used in this study. We evaluated here the ill-posedness of this classification problem across different dimensions and sample sizes and its relationship to the performance of regularized logistic regression (RLR, linear support vector machine (SVM and linear regression classifier (LRC. In addition, these methods were compared with their principal components space counterparts. PRINCIPAL FINDINGS: In voxel space the prediction performance of all methods increased as sample sizes increased. They were not only relatively robust to the increase of dimension, but they often showed improvements in accuracy. We linked this behavior to improvements in conditioning of the linear kernels matrices. In general the RLR and SVM performed similarly. Surprisingly, the LRC was often very competitive when the linear kernel matrices were best conditioned. Finally, when comparing these methods in voxel and principal component spaces, we did not find large differences in prediction performance. CONCLUSIONS AND SIGNIFICANCE: We analyzed the problem of classifying AD MRI images from the perspective of linear ill-posed problems. We demonstrate empirically the impact of the linear kernel matrix conditioning on different classifiers' performance. This dependence is characterized across sample sizes and dimensions. In this context we also show that increased dimensionality does not necessarily degrade

  19. Factors associated with the variability in caregiver assessments of the capacities of the patients with Alzheimer"s disease

    OpenAIRE

    Conde Sala, Josep Lluís; Reñé Ramírez, Ramon; Turró Garriga, Oriol; Gascón-Bayarri, J.; Juncadella i Puig, Montserrat; Moreno-Cordón, L.; Viñas Diez, V.; Vilalta Franch, Joan; Garre Olmo, Josep

    2013-01-01

    Abstract Background: Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer"s disease (AD). Objectives: To identify the caregiver variables associated with variability in their ratings of patients" capacities. Methods: Consecutive sample of 221 out-patients with AD and their family caregivers. The capacities evaluated by caregivers were: the degree of functional disability, using the Disability A...

  20. [Nutritional factors in prevention of Alzheimer's disease].

    Science.gov (United States)

    Wyka, Joanna

    2012-01-01

    Nutritional patterns affect significantly man's body at each age. The elderly--with their eating habits and diseases they have overcome--often require specific dietary intervention. A proper and well-balanced diet is an important element of lifestyle that may become a factor facilitating the so-called healthy, successful ageing and delay the development of noninfectious, chronic metabolic diseases that are in majority of cases diagnosed in elder people. Neurodegenerative diseases have been classified amongst chronic diseases yet with still controversial etiology. Nevertheless, it is speculated that some nutritional factors, including the appropriate intake of B-group vitamins, antioxidative vitamins and polyunsaturated fatty acids, are likely to play a significant role in their prevention and therapy. A diet rich in vegetables and fruits, whole-meal bread, milk and dairy products as well as containing fish, plant oils and nuts provides all indispensable nutrients. The appropriate merging of these food products into dishes--widely described in literature as the Mediterranean diet--facilitates leading a long life in health. PMID:22928359

  1. Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease

    Science.gov (United States)

    Yokoyama, Jennifer S.; Wang, Yunpeng; Schork, Andrew J.; Thompson, Wesley K.; Karch, Celeste M.; Cruchaga, Carlos; McEvoy, Linda K.; Witoelar, Aree; Chen, Chi-Hua; Holland, Dominic; Brewer, James B.; Franke, Andre; Dillon, William P.; Wilson, David M.; Mukherjee, Pratik; Hess, Christopher P.; Miller, Zachary; Bonham, Luke W.; Shen, Jeffrey; Rabinovici, Gil D.; Rosen, Howard J.; Miller, Bruce L.; Hyman, Bradley T.; Schellenberg, Gerard D.; Karlsen, Tom H.; Andreassen, Ole A.; Dale, Anders M.; Desikan, Rahul S.

    2016-01-01

    IMPORTANCE Late-onset Alzheimer disease (AD), the most common form of dementia, places a large burden on families and society. Although epidemiological and clinical evidence suggests a relationship between inflammation and AD, their relationship is not well understood and could have implications for treatment and prevention strategies. OBJECTIVE To determine whether a subset of genes involved with increased risk of inflammation are also associated with increased risk for AD. DESIGN, SETTING, AND PARTICIPANTS In a genetic epidemiology study conducted in July 2015, we systematically investigated genetic overlap between AD (International Genomics of Alzheimer’s Project stage 1) and Crohn disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, and psoriasis using summary data from genome-wide association studies at multiple academic clinical research centers. P values and odds ratios from genome-wide association studies of more than 100 000 individuals were from previous comparisons of patients vs respective control cohorts. Diagnosis for each disorder was previously established for the parent study using consensus criteria. MAIN OUTCOMES AND MEASURES The primary outcome was the pleiotropic (conjunction) false discovery rate P value. Follow-up for candidate variants included neuritic plaque and neurofibrillary tangle pathology; longitudinal Alzheimer’s Disease Assessment Scale cognitive subscale scores as a measure of cognitive dysfunction (Alzheimer’s Disease Neuroimaging Initiative); and gene expression in AD vs control brains (Gene Expression Omnibus data). RESULTS Eight single-nucleotide polymorphisms (false discovery rate P < .05) were associated with both AD and immune-mediated diseases. Of these, rs2516049 (closest gene HLA-DRB5; conjunction false discovery rate P = .04 for AD and psoriasis, 5.37 × 10−5 for AD, and 6.03 × 10−15 for psoriasis) and rs12570088 (closest gene IPMK; conjunction false discovery rate P = .009 for

  2. Low vitamin B-12 status in confirmed Alzheimer's disease as revealed by serum holotranscobalamin

    OpenAIRE

    Refsum, H.; Smith, A.

    2003-01-01

    Methods: 51 patients with pathologically confirmed Alzheimer's disease and 65 cognitively screened elderly controls were studied. Serum holotranscobalamin was measured by a new solid phase radioimmunoassay.

  3. Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD

    Directory of Open Access Journals (Sweden)

    Christopher L Edwards

    2007-01-01

    Full Text Available Christopher L Edwards1, Renee Dunn Raynor1, Miriam Feliu1, Camela McDougald1, Stephanie Johnson2, Donald Schmechel3, Mary Wood1, Gary G Bennett4, Patrick Saurona5, Melanie Bonner1, Chante’ Wellington1, Laura M DeCastro6, Elaine Whitworth6, Mary Abrams6, Patrick Logue1, Lekisha Edwards1, Salutario Martinez7, Keith E Whitfield81Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; 2American Psychological Association, Science Directorate, Washington, DC, USA; 3Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA; 4Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA; 5Taub Institute For Research on Alzheimer’s Disease and The Aging Brain, Columbia University, New York, NY, USA; 6Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, NC, USA; 7Department of Radiology, Duke University Medical Center, Durham, NC, USA; 8Duke University, Durham, NC, USAAbstract: Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.Keywords: cerebral vascular event, neuropsychological assessment, sickle cell disease, neuroimaging

  4. Targeting Gonadotropins: An Alternative Option for Alzheimer Disease Treatment

    Directory of Open Access Journals (Sweden)

    Gemma Casadesus

    2006-01-01

    Full Text Available Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of the disease. As such, the role of reproductive hormones, which are closely associated with the cell cycle both during development and after birth, may be of key import. While estrogen has been the primary focus, the protective effects of hormone replacement therapy on cognition and dementia only during a “crucial period” led us to expand the study of hormonal influences to other members of the hypothalamic pituitary axis. Specifically, in this review, we focus on luteinizing hormone, which is not only increased in the sera of patients with Alzheimer disease but, like estrogen, is modulated by hormone replacement therapy and also influences cognitive behavior and pathogenic processing in animal models of the disease. Targeting gonadotropins may be a useful treatment strategy for disease targeting multiple pleiotropic downstream consequences.

  5. Alzheimer's disease: is a vaccine possible?

    International Nuclear Information System (INIS)

    The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility

  6. Alzheimer's disease: is a vaccine possible?

    Energy Technology Data Exchange (ETDEWEB)

    Alves, R.P.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil); Yang, M.J. [Instituto Butantan, Laboratório de Genética, São Paulo, SP, Brasil, Laboratório de Genética, Instituto Butantan, São Paulo, SP (Brazil); Batista, M.T.; Ferreira, L.C.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-05-09

    The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

  7. Pharmacoeconomics of cholinesterase inhibitors in the treatment of Alzheimer's disease.

    Science.gov (United States)

    Jönsson, Linus

    2003-01-01

    Cholinesterase inhibitors constitute one of few treatment options available for Alzheimer's disease, the most common cause of dementia. The modest effects and relatively high acquisition costs of these drugs make the health economics of dementia an important subject of study. Simulation models can be used to bring together existing data and make predictions of the long-term cost effectiveness of treatment. Most models have been built around cognitive function as a key parameter based on the observed relationship between cognitive function and costs of care. Patients with more severe disease attain higher total costs of care. Also, these patients have a higher share of formal care costs than do patients with mild disease, who are usually looked after by informal caregivers. The valuation of unpaid care is controversial, and the choice of method may affect results considerably. Another important issue is the measurement of health-related QOL in patients with Alzheimer's disease. The few existing studies have used proxy respondents to elicit utility weights in different disease states; however, this methodology has not been validated. It is likely that the increased drug costs incurred by the use of cholinesterase inhibitors will be offset (at least partly) by savings in other healthcare costs. However, these results should be viewed as preliminary, since we are still awaiting data from long-term follow-up studies. Also, the value of treatment for patients and caregivers in terms of QOL improvements has yet to be established. PMID:13129415

  8. Inflammation and NF-kappa B in Alzheimer's Disease and Diabetes

    NARCIS (Netherlands)

    Granic, Ivica; Dolga, Amalia; Nijholt, Ingrid M.; van Dijk, Gertjan; Eisel, Ulrich L. M.

    2009-01-01

    Inflammatory processes are a hallmark of many chronic diseases including Alzheimer's disease and diabetes mellitus. Fairly recent statistical evidence indicating that type 2 diabetes increases the risk of developing Alzheimer's disease has led to investigations of the potential common processes that

  9. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - Therapeutic potential or a mirage?

    NARCIS (Netherlands)

    Gladkevich, A.; Bosker, F.; Korf, J.; Yenkoyan, K.; Vahradyan, H.; Aghajanov, M.

    2007-01-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experiment

  10. Alzheimer's Project

    Medline Plus

    Full Text Available ... Chicago National Alzheimer's Gala A Night at Sardi's Alzheimer's Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project ... help us change the way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on ...

  11. Alterations in metabolic properties in fibroblasts in Alzheimer disease.

    Science.gov (United States)

    Sorbi, S; Piacentini, S; Latorraca, S; Piersanti, P; Amaducci, L

    1995-01-01

    Alzheimer disease (AD) leads to alterations in several biochemical properties in cultured skin fibroblasts. Because abnormal glucose metabolism has been reported in both in vivo and in vitro studies of the brain, we examined glucose and glutamine oxidation and lactate production in cultured skin fibroblasts from nine patients with familial AD, 19 with sporadic AD, and 20 age-matched controls. The production of CO2 from glucose and glutamine was significantly lower in both groups of Alzheimer fibroblasts compared to controls after 10 min or 1, 2, and 4 h of incubation. The reduction in CO2 production was most evident after 1 h of incubation with either (U-14C)-glucose or (U-14C)-glutamine. Lactate concentration was comparable in all groups at any time of incubation. These findings suggest that processes that require mitochondrial function as glucose or glutamine oxidation are altered in AD and provide evidence that complex metabolic differences are expressed in cultured nonneuronal cells from Alzheimer patients. PMID:7662326

  12. The "Alzheimer's disease signature": potential perspectives for novel biomarkers

    Directory of Open Access Journals (Sweden)

    Zella Davide

    2011-09-01

    Full Text Available Abstract Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis.

  13. Stroke, Vascular Dementia, and Alzheimer's Disease: Molecular Links.

    Science.gov (United States)

    Vijayan, Murali; Reddy, P Hemachandra

    2016-09-01

    Stroke is a brain disease that occurs when blood flow stops, resulting in reduced oxygen supply to neurons. Stroke occurs at any time and at any age, but increases after the age of 55. It is the second leading cause of death and the third leading cause of disability-adjusted, life-years. The pathophysiology of ischemic stroke is complex and recent molecular, cellular, and animal models and postmortem brain studies have revealed that multiple cellular changes have been implicated, including oxidative stress/mitochondrial dysfunction, inflammatory responses, micro RNA alterations, and marked changes in brain proteins. These cellular changes provide new information for developing therapeutic strategies for ischemic stroke treatment. Research also revealed that stroke increases with a number of modifiable factors and most strokes can be prevented and/or controlled through pharmacological or surgical interventions and lifestyle changes. Ischemic stroke is the major risk factor for vascular dementia and Alzheimer's disease. This review summarizes the latest research findings on stroke, including causal factors and molecular links between stroke and vascular disease/Alzheimer's disease. PMID:27567871

  14. Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

    LENUS (Irish Health Repository)

    Hampel, H

    2012-02-01

    In the earliest clinical stages of Alzheimer\\'s Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.

  15. Voxel-Based Correlation between Coregistered Single-Photon Emission Computed Tomography and Dynamic Susceptibility Contrast Magnetic Resonance Imaging in Subjects with Suspected Alzheimer Disease

    Energy Technology Data Exchange (ETDEWEB)

    Cavallin, L.; Axelsson, R.; Wahlund, L.O.; Oeksengard, A.R.; Svensson, L.; Juhlin, P.; Wiberg, M. Kristoffersen; Frank, A. [Division of Radiology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden)

    2008-12-15

    Background: Current diagnosis of Alzheimer disease is made by clinical, neuropsychologic, and neuroimaging assessments. Neuroimaging techniques such as magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) could be valuable in the differential diagnosis of Alzheimer disease, as well as in assessing prognosis. Purpose: To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). Material and Methods: 24 patients, eight with AD, 10 with MCI, and six controls, were investigated with SPECT using {sup 99m}Tc-hexamethylpropyleneamine oxime (HMPAO, Ceretec; GE Healthcare Ltd., Little Chalsont UK) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a contrast-enhancing gadobutrol formula (Gadovist; Bayer Schering Pharma, Berlin, Germany). Voxel-based correlation between coregistered SPECT and DSC-MR images was calculated. Region-of-interest (ROI) analyses were then performed in 24 different brain areas using brain registration and analysis of SPECT studies (BRASS; Nuclear Diagnostics AB, Stockholm (SE)) on both SPECT and DSC-MRI. Results: Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. ROI analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and five regions in DSC-MR. Conclusion: SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer disease.

  16. Voxel-Based Correlation between Coregistered Single-Photon Emission Computed Tomography and Dynamic Susceptibility Contrast Magnetic Resonance Imaging in Subjects with Suspected Alzheimer Disease

    Energy Technology Data Exchange (ETDEWEB)

    Cavallin, L.; Axelsson, R.; Wahlund, L.O.; Oeksengard, A.R.; Svensson, L.; Juhlin, P.; Wiberg, M. Kristoffersen; Frank, A. (Division of Radiology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden))

    2008-12-15

    Background: Current diagnosis of Alzheimer disease is made by clinical, neuropsychologic, and neuroimaging assessments. Neuroimaging techniques such as magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) could be valuable in the differential diagnosis of Alzheimer disease, as well as in assessing prognosis. Purpose: To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). Material and Methods: 24 patients, eight with AD, 10 with MCI, and six controls, were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO, Ceretec; GE Healthcare Ltd., Little Chalsont UK) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a contrast-enhancing gadobutrol formula (Gadovist; Bayer Schering Pharma, Berlin, Germany). Voxel-based correlation between coregistered SPECT and DSC-MR images was calculated. Region-of-interest (ROI) analyses were then performed in 24 different brain areas using brain registration and analysis of SPECT studies (BRASS; Nuclear Diagnostics AB, Stockholm (Sweden)) on both SPECT and DSC-MRI. Results: Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. ROI analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and five regions in DSC-MR. Conclusion: SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer disease

  17. Why musical memory can be preserved in advanced Alzheimer's disease.

    Science.gov (United States)

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  18. Why musical memory can be preserved in advanced Alzheimer's disease.

    Science.gov (United States)

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  19. Genetic variants in Alzheimer disease - molecular and brain network approaches.

    Science.gov (United States)

    Gaiteri, Chris; Mostafavi, Sara; Honey, Christopher J; De Jager, Philip L; Bennett, David A

    2016-07-01

    Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID:27282653

  20. Alzheimer's disease: a mathematical model for onset and progression

    CERN Document Server

    Bertsch, Michiel; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2015-01-01

    In this paper we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium, and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Even though we deliberately neglect many aspects of the complexity of the brain and the disease, numerical simulations are in good qualitative agreement with clinical...