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Sample records for alzheimers disease neuroimaging

  1. Neuroimaging of Alzheimer's disease

    International Nuclear Information System (INIS)

    Main purposes of neuroimaging in Alzheimer's disease have been moved from diagnosis of advanced Alzheimer's disease to diagnosis of very early Alzheimer's disease at a prodromal stage of mild cognitive impairment, prediction of conversion from mild cognitive impairment to Alzheimer's disease, and differential diagnosis from other diseases causing dementia. Structural MRI studies and functional studies using fluorodeoxyglucose (FDG)-PET and brain perfusion SPECT are widely used in diagnosis of Alzheimer's disease. Outstanding progress in diagnostic accuracy of these neuroimaging modalities has been obtained using statistical analysis on a voxel-by-voxel basis after spatial normalization of individual scans to a standardized brain-volume template instead of visual inspection or a conventional region of interest technique. In a very early stage of Alzheimer's disease, this statistical approach revealed gray matter loss in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex. These two findings might be related in view of anatomical knowledge that the regions are linked through the circuit of Papez. This statistical approach also offers accurate evaluation of therapeutical effects on brain metabolism or perfusion. The latest development in functional imaging relates to the final pathological hallmark of Alzheimer's disease-amyloid plaques. Amyloid imaging might be an important surrogate marker for trials of disease-modifying agents. (author)

  2. Functional neuroimaging in Alzheimer's disease

    International Nuclear Information System (INIS)

    Recent progress in the title is reviewed often referring to authors' investigations. The method eZIS developed by them is for automated diagnosis of brain perfusion SPECT, where voxel-based analysis can be done using a Z-score map calculable from patient's data and standard database with 3D-stereotactic surface projection. Decreases of regional cerebral blood flow (rCBF) and of glucose metabolism detectable in specified brain regions by PET or SPECT in patients with mild cognitive impairment (MCI), are found useful for predicting the stage progression of MCI to Alzheimer disease (AD) in future. Partial volume correction method, essentially the division of images of a gray matter SPECT by MR, has elevated the precision of cerebral image analysis. Differential diagnosis of AD and dementia with Lewy bodies, the second most common form of dementia, is possible by the difference of occipital perfusion or glucose metabolism. Evidences by rCBF SPECT as well as by symptomatic ones have been accumulated recently for the therapeutic effect of donepezil, an inhibitor of acetylcholine esterase used for AD treatment. PET and SPECT imaging for the assessment of rCBF and metabolism has thus played very important roles in AD diagnosis, staging, differentiation, prediction and drug effect assessment. Recent advance in voxel-based statistical analysis of PET and SPECT images has raised the value of neuroimaging in dementia. (T.I.)

  3. 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.

  4. The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort

    OpenAIRE

    A. Caroli; Frisoni, G B

    2010-01-01

    The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Aβ 1–42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarke...

  5. 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, and...

  6. 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)

  7. To differentiate Alzheimer's disease earlier: introduction of Alzheimer's Disease Neuroimaging Initiative (ADNI

    Directory of Open Access Journals (Sweden)

    Zhi-gang QI

    2014-04-01

    Full Text Available Alzheimer's disease (AD brought about much pressure in modern aging society both economically and psychologically, so it is meaningful to carry out AD research. Being considered as the most successful multi-center, inter-disciplinary and longitudinal research in AD field, Alzheimer's Disease Neuroimaging Initiative (ADNI has obtained outstanding achievements. In this review, we attempt to introduce the research plan of ADNI project for reference. doi: 10.3969/j.issn.1672-6731.2014.04.003

  8. 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.

  9. 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)

  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. PMID:24142306

  11. Applied Neuroimaging to the Diagnosis of Alzheimer's Disease: A Multicriteria Model

    Science.gov (United States)

    Tamanini, Isabelle; de Castro, Ana Karoline; Pinheiro, Plácido Rogério; Pinheiro, Mirian Calíope Dantas

    In the last few years, Alzheimer's disease has been the most frequent cause of dementia and it is responsible, alone or in association with other diseases, for 50% of the cases in western countries. Dementias are syndromes characterized by a decline in memory and other neuropsychological changes, especially occurring in elderly people and increasing exponentially along the aging process. The main focus of this work is to develop a multicriteria model for aiding in decision making on the diagnosis of Alzheimer's disease by using the Aranau Tool, structured on the Verbal Decision Analysis. In this work, the modeling and evaluation processes were conducted with the aid of a medical expert, bibliographic sources and questionnaires. The questionnaires taken into account were based mainly on patients' neuroimaging tests, and we analyzed wheter or not there were problems in the patients' brain that could be relevant to the diagnosis of Alzheimer's disease.

  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. 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......: Six academic EADC centres recruited 49 subjects (healthy controls, subjects with mild cognitive impairment (MCI) and AD). We measured CSF beta-amyloid 42 (CSF Abeta42), total tau-protein (t-tau), phosphorylated tau-proteins (P-tau181, P-tau231), plasma beta-amyloid 40 and 42 (Abeta40/Abeta42......). Immediate fresh shipment was compared to freezing and later shipment on dry ice. RESULTS: CSF T-tau (fresh samples) was increased in AD versus controls (p=0.049), CSF Abeta42 (frozen samples) was decreased in MCI and AD (p=0.02), as well as plasma Abeta40 (fresh and frozen samples) in AD (p=0.049 and p=0...

  15. 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)....

  16. 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)....

  17. About Alzheimer's Disease: Alzheimer's Basics

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Alzheimer's Basics What is Alzheimer's disease? What happens to ... with Alzheimer's disease? What is dementia? What is Alzheimer's disease? Alzheimer’s disease is an irreversible, progressive brain ...

  18. 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

  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. 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

  1. 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.

  2. 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...

  3. 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. PMID:26776178

  4. 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 ...

  5. 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 ...

  6. Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

    Science.gov (United States)

    Tan, Lin; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Chen-Chen; Zhu, Xi-Chen; Miao, Dan; Yu, Wan-Jiang; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2016-01-01

    The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD. PMID:27229352

  7. 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

  8. 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 ...

  9. About Alzheimer's Disease: Treatment

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Treatment How is Alzheimer's disease treated? What ... being researched? What are clinical trials? How is Alzheimer's disease treated? Alzheimer's disease is complex, and it ...

  10. About Alzheimer's Disease: Symptoms

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Symptoms Early signs and symptoms Mild Alzheimer's ... more about other early signs of Alzheimer's » Mild Alzheimer's disease As the disease progresses, people experience greater ...

  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. Alzheimer's Disease Genetics

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Genetics Fact Sheet The Genetics of Disease ...

  13. 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)

  14. Alzheimer's Disease Medications

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Medications Fact Sheet Treatment for Mild to ...

  15. Understanding Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... National Alzheimer's Project Act (NAPA) About ADEAR Understanding Alzheimer's Disease: What You Need to Know Introduction Many ...

  16. Alzheimer's Disease Research Centers

    Science.gov (United States)

    ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease Research Centers The National Institute on Aging ... Repository for Alzheimer's Disease ADC Directory Arizona Arizona Alzheimer’s Disease Center/Sun Health Research Institute Eric Reiman, ...

  17. 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, ...

  18. About Alzheimer's Disease: Diagnosis

    Science.gov (United States)

    ... National Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Diagnosis What should I do if I’ ... I'm worried about memory loss or possible Alzheimer's? If you are concerned about changes in memory ...

  19. PET neuroimaging studies of [(18)F]CABS13 in a double transgenic mouse model of Alzheimer's disease and nonhuman primates.

    Science.gov (United States)

    Liang, Steven H; Holland, Jason P; Stephenson, Nickeisha A; Kassenbrock, Alina; Rotstein, Benjamin H; Daignault, Cory P; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M; Vasdev, Neil

    2015-04-15

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([(18)F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the "metal hypothesis of Alzheimer's disease". Herein, a practical radiosynthesis of [(18)F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [(18)F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [(18)F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 min. Temporal PET neuroimaging studies were carried out in female transgenic B6C3-Tg(APPswe,PSEN 1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7, and 10 months of age. [(18)F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal nonhuman primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable (18)F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  20. Alzheimer's Disease: Unraveling the Mystery

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer's Disease: Unraveling the Mystery Preface Over the past ...

  1. 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: ...

  2. 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 ...

  3. Role of neuroimaging in multidisciplinary approach towards Non-Alzheimer's dementia.

    Science.gov (United States)

    Patro, Satya Narayana; Glikstein, Rafael; Hanagandi, Prasad; Chakraborty, Santanu

    2015-10-01

    Dementia is defined as chronic deterioration of intellectual function and cognitive skills significant enough to interfere with the ability to perform daily activities. Recent advances in the treatment of dementia have renewed interest in the use of various neuroimaging techniques that can assist in the diagnosis and differentiation of various subtypes. Neuroimaging and computational techniques have helped the radiological community to monitor disease progression of various neurodegenerative conditions presenting with dementia, such as Alzheimer disease, frontotemporal lobe dementia (FTLD), progressive supranuclear palsy (PSP) and multisystem atrophy-cerebellar variant (MSA-C), and their response to newer therapies. Prompt identification of treatable or reversible forms of dementia, such as tumours, subdural haemorrhage and intracranial dAVF, is crucial for the effective management of these conditions. It is also prudent to recognize the imaging spectrum of metabolic, infective and autoimmune diseases with rapidly progressing dementia, such as methanol toxicity, central pontine myelinolysis (CPM), delayed post hypoxic leukoencephalopathy (DPHL), HIV, Creutzfeldt-Jakob Disease (CJD), Sjogren's syndrome, multiple sclerosis (MS), radiation necrosis and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which are difficult to treat and often require palliative care. This pictorial review emphasizes various non-Alzheimer's dementia entities and discusses their imaging highlights. Teaching Points • Non Alzheimer's dementia constitutes a broad spectrum of conditions. • Neuroimaging plays an important role in differentiating treatable from irreversible dementia. • Neuroimaging is often non-specific in early stages of neurodegenerative conditions with dementia. • Neuroimaging plays an important role in the multimodal approach towards management of dementia. PMID:26206249

  4. 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...

  5. About Alzheimer's Disease: Causes

    Science.gov (United States)

    ... Project Act (NAPA) About ADEAR About Alzheimer's Disease: Causes Age-related changes in the brain Genetics Health, ... for the Causes of AD" NIA Information on Causes Alzheimer’s Disease in People with Down Syndrome Understanding ...

  6. 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...... trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded...... therapeutic or preventive strategies for Alzheimer's disease....

  7. Neuroimaging abnormalities in Griscelli's disease

    International Nuclear Information System (INIS)

    Griscelli's disease is a rare autosomal recessive immunodeficiency syndrome. We report a 7-1/2-month-old white girl who presented with this syndrome, but initially without neurological abnormalities. Initial CT of the brain was normal. Despite haematological remission with chemotherapy, she developed neurological symptoms, progressing to coma. At this time, CT showed areas of coarse calcification in the globi pallidi, left parietal white matter and left brachium pontis. Hypodense areas were present in the genu and posterior limb of the internal capsule on the right side, as well as posterior aspects of both thalami, together with minimal generalised atrophy. MRI revealed areas of increased T2 signal and a focal area of abnormal enhancement in the subcortical white matter. Griscelli's disease should be added to the list of acquired neuroimaging abnormalities in infants. (orig.)

  8. Alzheimer's disease and stigmatization

    OpenAIRE

    Dimitrios Kosmidis; Aggeliki Nousi; Stavros Τoulis; Antigoni Fountouki; Dimitrios Theofanidis

    2012-01-01

    Aim: The main objective of the study was to explore social bias experienced by patients with Alzheimer's disease and to investigate the knowledge of a sample of the general population regarding this particular disease. Method: The sample consisted of 91 individuals who were first degree relatives of members of three Centers of Open Protection for the Elderly, who did not suffer from dementia as they have recently undergone screening for Alzheimer's disease. A survey design was adopted using a...

  9. 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 ...

  10. 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

  11. 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...

  12. Neuropathology of Alzheimer's Disease

    Science.gov (United States)

    Perl, Daniel P.

    2010-01-01

    Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rod-like bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease–related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. PMID:20101720

  13. 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 ...

  14. 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.)

  15. 2014-2015 Alzheimer's Disease Progress Report

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Alzheimer's Project Act (NAPA) About ADEAR 2014-2015 Alzheimer's Disease Progress Report: Advancing Research Toward a Cure ...

  16. Prediabetes and Alzheimer's Disease

    Science.gov (United States)

    Bitra, V. R.; Rapaka, Deepthi; Akula, Annapurna

    2015-01-01

    Aging patients with diabetes are at higher risk of developing Alzheimer's disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimer's disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimer's abnormalities. PMID:26798163

  17. Prediabetes and alzheimer's disease

    Directory of Open Access Journals (Sweden)

    V R Bitra

    2015-01-01

    Full Text Available Aging patients with diabetes are at higher risk of developing Alzheimer's disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimer's disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimer's abnormalities.

  18. 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...

  19. Genetics of Alzheimer Disease

    OpenAIRE

    Bekris, Lynn M.; Yu, Chang-En; Bird, Thomas D.; Tsuang, Debby W.

    2010-01-01

    Alzheimer disease (AD) is the most common causes of neurodegenerative disorder in the elderly individuals. Clinically, patients initially present with short-term memory loss, subsequently followed by executive dysfunction, confusion, agitation, and behavioral disturbances. Three causative genes have been associated with autosomal dominant familial AD (APP, PSEN1, and PSEN2) and 1 genetic risk factor (APOEε4 allele). Identification of these genes has led to a number of animal models that have ...

  20. 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......'s degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid...

  1. Magnetic resonance imaging of Alzheimer's disease

    International Nuclear Information System (INIS)

    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.)

  2. 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...

  3. [Immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  4. Preventing Alzheimer's Disease: What Do We Know?

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... National Alzheimer's Project Act (NAPA) About ADEAR Preventing Alzheimer’s Disease: What Do We Know? Introduction The news ...

  5. Alzheimer's Disease in People with Down Syndrome

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s ... Plan National Alzheimer's Project Act (NAPA) About ADEAR Alzheimer’s Disease in People with Down Syndrome People with ...

  6. 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 ...

  7. 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

  8. 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.

  9. Alzheimer's disease and stigmatization

    Directory of Open Access Journals (Sweden)

    Dimitrios Kosmidis

    2012-04-01

    Full Text Available Aim: The main objective of the study was to explore social bias experienced by patients with Alzheimer's disease and to investigate the knowledge of a sample of the general population regarding this particular disease. Method: The sample consisted of 91 individuals who were first degree relatives of members of three Centers of Open Protection for the Elderly, who did not suffer from dementia as they have recently undergone screening for Alzheimer's disease. A survey design was adopted using a face-to-face questionnaire which apart from the demographical data and two open-ended questions, was based on a 5-point lickert scale, looking at knowledge, attitudes and stigma towards the disease. Data was analyzed through SPSS software using descriptive statistics while results were regarded significant at p<0,05 level of significance Results: For the quantitave questions, cronbach's a was a=0,75 and the average discrete index 0,31. Stigma was explored through a series of direct and in-direct questions and while 70 (77% persons distinguish dementia from mental illness, 9(9,9% people did not answer these questions. The majority (62,6% did not stigmatize the patient as 57 persons said that the patient is not to blame for the disease. Conclusions: from the distribution of results it becomes evident that there is a need for education, training and multifaceted enlightenment of the general population on issues concerning mental health. Answers that implied tendencies of marginalization of patients with dementia emanated mainly came from individuals in the sample with limited knowledge of the illness and relatively low educational background.

  10. Home Safety for People with Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  11. Adapting Activities for People with Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  12. Keeping the Person with Alzheimer's Disease Safe

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  13. The role of SPECT in the diagnosis of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, G.P. [Sydney Univ, Sydney, NSW (Australia). School of Medical radiation Technology

    1997-03-01

    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.

  14. The immunotherapy of Alzheimer's disease

    OpenAIRE

    Weksler Marc E

    2004-01-01

    Abstract Only a small percentage of patients with Alzheimer's disease benefit from current drug therapy and for only a relatively short time. This is not surprising as the goal of these drugs is to enhance existing cerebral function in Alzheimer patients and not to block the progression of cognitive decline. In contrast, immunotherapy is directed at clearing the neurotoxic amyloid beta peptide from the brain that directly or indirectly leads to cognitive decline in patients with Alzheimer's d...

  15. 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

  16. 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

  17. 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…

  18. The immunotherapy of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Weksler Marc E

    2004-11-01

    Full Text Available Abstract Only a small percentage of patients with Alzheimer's disease benefit from current drug therapy and for only a relatively short time. This is not surprising as the goal of these drugs is to enhance existing cerebral function in Alzheimer patients and not to block the progression of cognitive decline. In contrast, immunotherapy is directed at clearing the neurotoxic amyloid beta peptide from the brain that directly or indirectly leads to cognitive decline in patients with Alzheimer's disease. The single trial of active immunization with the amyloid beta peptide provided suggestive evidence of a reduction in cerebral amyloid plaques and of stabilization in cognitive function of half the patients who developed good antibody responses to the amyloid beta peptide. However, 6% of actively immunized Alzheimer patients developed sterile meningoencephalitis that forced the cessation of the clinical trial. Passive immunotherapy in animal models of Alzheimer's disease has provided similar benefits comparable to those seen with active immunotherapy and has the potential of being effective in the half of Alzheimer's disease patients who do not make a significant anti-amyloid beta peptide antibody response and without inducing T-cell-mediated encephalitis. Published studies of 5 patients with sporadic Alzheimer disease treated with intravenous immunoglobulin containing anti-amyloid beta peptide antibodies showed that amyloid beta peptide was mobilized from the brain and cognitive decline was interrupted. Further studies of passive immunotherapy are urgently required to confirm these observations.

  19. [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

  20. About Alzheimer's Disease: Risk Factors and Prevention

    Science.gov (United States)

    ... Alzheimer's Project Act (NAPA) About ADEAR About Alzheimer's Disease: Risk Factors and Prevention We can’t control some risk factors for ... Preventing Alzheimer’s Disease: What Do We Know? Alzheimer's Disease: Unraveling the Mystery ... Factors and Prevention News Summit sets the path ahead for Alzheimer's ...

  1. 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 ...

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

    DEFF Research Database (Denmark)

    Sørensen, Lauge Emil Borch Laurs; 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...... 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...

  3. 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

  4. [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

  5. Biomarkers for Alzheimer's disease therapeutic trials.

    Science.gov (United States)

    Hampel, Harald; Wilcock, Gordon; Andrieu, Sandrine; Aisen, Paul; Blennow, Kaj; Broich, K; Carrillo, Maria; Fox, Nick C; Frisoni, Giovanni B; Isaac, Maria; Lovestone, Simon; Nordberg, Agneta; Prvulovic, David; Sampaio, Christina; Scheltens, Philip; Weiner, Michael; Winblad, Bengt; Coley, Nicola; Vellas, Bruno

    2011-12-01

    The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials. PMID:21130138

  6. 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.

  7. [Language Symptoms of Alzheimer's Disease].

    Science.gov (United States)

    Shinagawa, Shunichiro

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by progressive memory disturbance. Language symptoms are considered to be less disease specific and therefore did not attract many researchers, interest until recently. Typical patients with AD present amnesic aphasia in the early disease stage followed by transcortical sensory aphasia; however, their language symptoms are varied. Recently, the concept of logopenic variant of primary progressive aphasia (PPA) has been developed, which is reported to have Alzheimer's neuropathology. Clinicians should verify patients' language abilities, as language can be the key to reveal their true cognitive functions. PMID:27156508

  8. 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 ...

  9. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao

    2014-01-01

    Full Text Available Alzheimer Disease (AD is an outcome as well as source of many diseases. Alzheimer is linked with many other diseases like Diabetes type 2, cholesterolemia, hypertension and many more. But how each of these diseases affecting other is still unknown to scientific community. Signaling Pathways of one disease is interlinked with other disease. But to what extent healthy brain is affected when any signaling in human body is disturbed is the question that matters. There is a need of Pathway analysis, Protein-Protein interaction (PPI and the conserved interactome study in AD and linked diseases. It will be helpful in finding the potent drug or vaccine target in conscious manner. In the present research the Protein-Protein interaction of all the proteins involved in Alzheimer Disease is analyzed using ViSANT and osprey tools and pathway analysis further reveals the significant genes/proteins linking AD with other diseases.

  10. 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.

  11. 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)

  12. Genetic heterogeneity and Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Schellenberg, G.D.; Wijsman, E.M. [Univ. of Washington, Seattle (United States); Bird, T.D. [Veteran`s Affairs Medical Center, Seattle, WA (United States)

    1994-09-01

    In some early-onset Alzheimer`s disease (AD) families, inheritance is autosomal dominant. (Early-onset AD is arbitarily defined as onset at {le} 60 years.) Two loci have been identified which are causative for early-onset familial AD (FAD). One is the amyloid precursor protein gene in which specific mutation have been identified. The second is a locus at 14q24.3 (AD3) which has been localized by linkage analysis; the gene and specific mutations have not been identified. Linkage studies place this locus between D14S61 and D14S63. These 2 loci, however, do not account for all early-onset FAD. The Volga German (VG) kindreds are descendants of families which emigrated from Germany to the Volga river region of Russia and subsequently to the US; AD in these families is hypothesized to be the result of a common genetic founder. The average age-at-onset in these families is 57 years. Linkage analysis for this group has been negative for the APP gene and for chromosome 14 markers. Thus, there is at least 1 other early-onset FAD locus. Recently, the {epsilon}4 allele of apolipoprotein E (ApoE) was identified as a risk-factor for late-onset AD. In a series of 53 late-onset kindreds, a strong genetic association was observed between the ApoE {epsilon}4 allele and AD. However, when linkage analysis was performed using a highly polymorphic locus at the ApoCII gene, which is within 30 kb of ApoE, significant evidence for co-segregation was not observed. This and other data suggests that while ApoE is an age-at-onset modifying locus, another gene(s), located elsewhere, contribute(s) to late-onset AD. Thus, there is probably at least 1 other late-onset locus. Once the VG locus is identified, it will be possible to determine whether an allelic variant of this locus is responsible for late-onset FAD.

  13. 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

  14. 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.

  15. Immunotherapeutic Approaches to Alzheimer's Disease

    Science.gov (United States)

    Monsonego, Alon; Weiner, Howard L.

    2003-10-01

    Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.

  16. Glycation in Parkinson's disease and Alzheimer's disease.

    Science.gov (United States)

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  17. Application of pattern classification in the diagnosis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Min-yue CHI

    2015-07-01

    Full Text Available Alzheimer's disease (AD is a common neurodegenerative disease in the elderly. Early diagnosis and prediction plays an important role in early intervention and delaying disease progression of AD. This paper focused on the principles and process of pattern classification method, and its application in the clinical study and auxiliary diagnosis of AD. The biomarkers, neuroimaging and cognitive ability scales are important features for pattern classification. Various classification algorithms including Bayesian networks, decision trees, support vector machines (SVM and multilayer perception have been adopted to distinguish AD, mild cognitive impairment (MCI and normal aging subjects. Besides, they can effectively trace and analyze MCI patients.

  18. Endocannabinoid signalling in Alzheimer's disease.

    Science.gov (United States)

    Maroof, Nazia; Pardon, Marie Christine; Kendall, David A

    2013-12-01

    The ECs (endocannabinoids) AEA (anandamide) and 2-AG (2-arachidonoylglycerol) and their lipid congeners OEA (N-oleoylethanolamide) and PEA (N-palmitoylethanolamide) are multifunctional lipophilic signalling molecules. The ECs, OEA and PEA have multiple physiological roles including involvement in learning and memory, neuroinflammation, oxidative stress, neuroprotection and neurogenesis. They have also been implicated in the pathology of, or perhaps protective responses to, neurodegenerative diseases. This is particularly the case with Alzheimer's disease, the most common age-related dementia associated with impairments in learning and memory accompanied by neuroinflammation, oxidative stress and neurodegeneration. The present mini-review examines the evidence supporting the roles that ECs appear to play in Alzheimer's disease and the potential for beneficial therapeutic manipulation of the EC signalling system. PMID:24256258

  19. 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 ...

  20. Frontotemporal dementia to Alzheimer's disease

    OpenAIRE

    Silveri, Maria Caterina

    2007-01-01

    Behavioral manifestations may dominate the clinical picture of the frontal variant of frontotemporal dementia (fv-FTD) for a long time before the appearance of true cognitive deficits. On the other hand, a deficit in the episodic memory domain represents the main manifestation of Alzheimer's disease (AD), Many behavioral disorders have been described in the clinical course of both FTD and AD; however, apathy and personality changes characterize frontal dementias, while depression dominates in...

  1. Inflammatory process in Alzheimer's Disease

    OpenAIRE

    MARCO ANTONIO MERAZ RIOS; DANIRA TORAL-RIOS; DIANA FRANCO-BOCANEGRA; VICTORIA CAMPOS-PEÑA

    2013-01-01

    Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs) surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ), a small fragment of 4...

  2. 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

  3. 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.)

  4. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. PMID:25459121

  5. Neurogenesis and Alzheimer's Disease

    OpenAIRE

    Philippe Taupin

    2006-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS)...

  6. The Importance of Adipokines in Alzheimer's Disease

    OpenAIRE

    Seyid Ahmet Ay; Ferhat Deniz; Kamil Baskoy; Arif Yonem

    2015-01-01

    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 var...

  7. Alzheimer's disease and periodontitis - an elusive link

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2014-01-01

    Full Text Available Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

  8. Neurotransmitter replacement therapy in Alzheimer's disease.

    OpenAIRE

    Mohr, E; Mendis, T; Rusk, I N; Grimes, J. D.

    1994-01-01

    The relative success of symptomatic attenuation of motor dysfunction in Parkinson's disease with dopaminomimetics has spurred interest in neurotransmitter replacement therapy for treating Alzheimer's disease. While cholinergic dysfunction has been linked to various clinical parameters in Alzheimer's disease, cholinergic replacement, including precursor therapy, administration of direct-acting agonists and inhibition of enzymatic degradation has had only very modest success. The inhibition of ...

  9. 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 ...

  10. 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...

  11. [Antibody therapy for Alzheimer's disease].

    Science.gov (United States)

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  12. 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?

  13. 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

  14. 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.

  15. Finding the Right Place for the Person with Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  16. Home Safety for People with Alzheimer's Disease: Driving

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  17. Legal and Financial Planning for People with Alzheimer's Disease

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  18. Understanding How Alzheimer's Disease Changes People: Challenges and Coping Strategies

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  19. Home Safety for People with Alzheimer's Disease: Natural Disaster Safety

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  20. Home Safety for People with Alzheimer's Disease: General Safety Concerns

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  1. Facilitating Alzheimer disease research recruitment.

    Science.gov (United States)

    Grill, Joshua D; Galvin, James E

    2014-01-01

    Alzheimer disease (AD) research faces challenges to successful enrollment, especially to clinical trials and biomarker studies. Failure to recruit the planned number of participants in a timely manner threatens the internal validity and success of clinical research, raising concerns about external validity and generalizability of results, and possibly leading to disparities in disease treatment. Methods to improve recruitment exist, but require varying levels of staff effort and financial resources, and evidence of effectiveness is often lacking or inconsistent. In this review, we summarize some of the available methods to improve AD research recruitment, the available literature to support or refute these strategies, and some of the experiences at the authors' AD Research Centers. We discuss the use of community-based participatory research principles and participant registries as a means to enhance research enrollment and increase diversity of research samples. PMID:24322484

  2. 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 ...

  3. The age factor in Alzheimer's disease.

    Science.gov (United States)

    Guerreiro, Rita; Bras, Jose

    2015-01-01

    Alzheimer's disease is the most common type of dementia, and it is characterized by a decline in memory or other thinking skills. The greatest risk factor for Alzheimer's disease is advanced age. A recent genome-wide study identified a locus on chromosome 17 associated with the age at onset, and a specific variant in CCL11 is probably responsible for the association. The association of a protective haplotype with a 10-year delay in the onset of Alzheimer's disease and the identification of a CCL11 variant with possible functional roles in this association might allow the future development of immunomodulators with the potential to halve disease incidence. PMID:26482651

  4. 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

  5. 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) in the...

  6. APP processing in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Zhang Yun-wu

    2011-01-01

    Full Text Available Abstract An important pathological feature of Alzheimer's disease (AD is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ. Multiple lines of evidence demonstrate that overproduction/aggregation of Aβ in the brain is a primary cause of AD and inhibition of Aβ generation has become a hot topic in AD research. Aβ is generated from β-amyloid precursor protein (APP through sequential cleavages first by β-secretase and then by γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα and preclude Aβ generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites.

  7. The genetics of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Bagyinszky E

    2014-04-01

    Full Text Available Eva Bagyinszky,1 Young Chul Youn,2 Seong Soo A An,1,* SangYun Kim3,*1Department of BioNano Technology Gachon University, Gyeonggi-do, 2Department of Neurology, Chung-Ang University College of Medicine, Seoul, 3Department of Neurology, Seoul National University Budang Hospital, Gyeonggi-do, South Korea*These authors contributed equally to this workAbstract: Alzheimer's disease (AD is a complex and heterogeneous neurodegenerative disorder, classified as either early onset (under 65 years of age, or late onset (over 65 years of age. Three main genes are involved in early onset AD: amyloid precursor protein (APP, presenilin 1 (PSEN1, and presenilin 2 (PSEN2. The apolipoprotein E (APOE E4 allele has been found to be a main risk factor for late-onset Alzheimer's disease. Additionally, genome-wide association studies (GWASs have identified several genes that might be potential risk factors for AD, including clusterin (CLU, complement receptor 1 (CR1, phosphatidylinositol binding clathrin assembly protein (PICALM, and sortilin-related receptor (SORL1. Recent studies have discovered additional novel genes that might be involved in late-onset AD, such as triggering receptor expressed on myeloid cells 2 (TREM2 and cluster of differentiation 33 (CD33. Identification of new AD-related genes is important for better understanding of the pathomechanisms leading to neurodegeneration. Since the differential diagnoses of neurodegenerative disorders are difficult, especially in the early stages, genetic testing is essential for diagnostic processes. Next-generation sequencing studies have been successfully used for detecting mutations, monitoring the epigenetic changes, and analyzing transcriptomes. These studies may be a promising approach toward understanding the complete genetic mechanisms of diverse genetic disorders such as AD.Keywords: dementia, amyloid precursor protein, presenilin 1, presenilin 2, APOE, mutation, diagnosis, genetic testing

  8. 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... Alzheimer's disease. Coordinate Alzheimer's disease research and services across all federal...

  9. 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.

  10. 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.

  11. 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.)

  12. 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.

  13. 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

  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. Neuroprotective peptides related to Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Slaninová, Jiřina; Borovičková, Lenka; Krejčová, G.; Patočka, J.

    2004-01-01

    Roč. 10, S (2004), s. H33. ISSN 1075-2617. [Hellenic Forum on Bioactive Peptides /4./. 22.04.2004-24.04.2004, Patras-Hellas] Keywords : neuroprotective peptides * Alzheimer's disease Subject RIV: CE - Biochemistry

  16. 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 ( 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...

  17. 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.

  18. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Alzheimer's Disease URL of this page: https://medlineplus.gov/languages/alzheimersdisease.html Other topics A-Z A B ...

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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)

  4. 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

  5. [Aβ immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

    Alzheimer's disease (AD) is one of the neurodegenerative diseases characterized by the deposition of amyloid-β-protein (Aβ) as senile plaques in the brain parenchyma and phosphorylated-tau accumulation as neurofibrillary tangles in the neurons. Although details of the disease pathomechanisms remain unclear, Aβ likely acts as a key protein for AD initiation and progression, followed by abnormal tau phosphorylation and neuronal death (amyloid-cascade hypothesis). According to this hypothesis, Aβ immunization therapies are created to eliminate Aβ from the brain, and to prevent the neurons from damage by these pathogenic proteins. There are two methods for Aβ immunotherapies: active and passive immunization. Previous studies have shown Aβ removal and improved cognitive function in animal models of AD. Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. On the contrary, side effects emerged, such as meningoencephalitis, vasogenic edema, which are currently called amyloid related imaging abnormalities (ARIA)-E and microhemorrhage (ARIA-H). In neuropathological studies of immunized cases, Aβ was removed from the brain parenchyma and phosphorylated-tau was reduced in the neuronal processes. Moreover, deterioration of the cerebral amyloid angiopathy (CAA) and an increase of microhemorrhages and microinfarcts were described. Aβ is cleared from the brain mainly via the lymphatic drainage pathway. ARIA could stem from severe CAA due to dysfunction of the drainage pathway after immunotherapy. Aβ immunization has a potential of cure for AD patients, although the above-described problems must be overcome before applying this therapy in clinical treatment. PMID:23568994

  6. Cognitive debt and Alzheimer's disease.

    Science.gov (United States)

    Marchant, Natalie L; Howard, Robert J

    2015-01-01

    We propose the concept of Cognitive Debt to characterize thoughts and behaviors that increase vulnerability to symptomatic Alzheimer's disease (AD). Evidence indicates that depression, anxiety, sleep disorder, neuroticism, life stress, and post-traumatic stress disorder increase risk for AD, and we suggest they do so by increasing Cognitive Debt. Repetitive negative thinking (RNT), a behaviorally measurable process common to these factors, may drive Cognitive Debt acquisition. RNT transcends disorder-specific definition, encompasses rumination and worry, and is defined by perseverative, negative thought tendencies. Evidence of dysregulated stress responses supports the concept of Cognitive Debt, of RNT as its causal mechanism, and of an interaction with the APOE-ε4 genotype to increase vulnerability to clinical AD, independent from traditional AD pathology. Defining a more specific behavioral profile of risk would enable interventions to be targeted earlier and more precisely at individuals most vulnerable to developing AD. Additionally, modulating RNT could potentially reduce risk of clinical AD. Interventions to reduce RNT are discussed, as are suggestions for future research. For these reasons we submit that the Cognitive Debt model may aid understanding of the psychological mechanisms that potentially increase predisposition to AD. PMID:25362035

  7. 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

  8. 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

  9. 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.

  10. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... 简体中文) Chinese - Traditional (繁體中文) French (français) German (Deutsch) Hindi (हिन्दी) Italian (italiano) Japanese (日本語) Korean (한국어) ... Gehirn: Eine interaktive Tour - Deutsch (German) Alzheimer's Association Hindi (हिन्दी) Alzheimer's Disease हिन्दी (Hindi) Bilingual ...

  11. 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)

  12. Raman spectroscopy of Alzheimer's diseased tissue

    Science.gov (United States)

    Sudworth, Caroline D.; Krasner, Neville

    2004-07-01

    Alzheimer's disease is one of the most common forms of dementia, and causes steady memory loss and mental regression. It is also accompanied by severe atrophy of the brain. However, the pathological biomarkers of the disease can only be confirmed and examined upon the death of the patient. A commercial (Renishaw PLC, UK) Raman system with an 830 nm NIR diode laser was used to analyse brain samples, which were flash frozen at post-mortem. Ethical approval was sought for these samples. The Alzheimer's diseased samples contained a number of biomarkers, including neuritic plaques and tangles. The Raman spectra were examined by order to differentiate between normal and Alzheimer's diseased brain tissues. Preliminary results indicate that Alzheimer's diseased tissues can be differentiated from control tissues using Raman spectroscopy. The Raman spectra differ in terms of peak intensity, and the presence of a stronger amide I band in the 1667 cm-1 region which occurs more prominently in the Alzheimer's diseased tissue. These preliminary results indicate that the beta-amyloid protein originating from neuritic plaques can be identified with Raman spectroscopy.

  13. 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

  14. Geriatric Dentistry and the Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Marcelo Coelho GOIATO

    2006-08-01

    Full Text Available Introduction: The world population is getting old, mainly in countries in development like Brazil. So, the number of pathologies, which appears in the elderly, will happen in a higher frequency. Among these diseases, we can point Alzheimer, an irreversible dementia, that has been related to age, cerebral vascular disease, stroke, immunological defects and to genetic factors (Down Syndrome. It is known that with the progression of dementia, patients present difficulties of oral hygiene caused by decrease of motor and cognitive functions of Alzheimer's bearers. These patients demand specific strategies for a dental treatment without bigger difficulties. Objective: the aim of this paper was to review the articles about the relationship of geriatric dentistry and Alzheimer disease focusing and the characteristics of the patients with this kind of dementia and the cares to them. For this purpose, a peer-reviewed literature was completed using Medline database for the period from 1972 to 2006, including alzheimer disease and dentistry, and BBO for the period from 1987 to 2004, with geriatric keyword. Conclusion: The available data indicate that individuals with Alzheimer disease have more oral health problems than individuals without dementia.

  15. 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.

  16. Progress Report on Alzheimer's Disease: Volume II.

    Science.gov (United States)

    National Inst. on Aging (DHHS/PHS), Bethesda, MD.

    This document provides an overview of the state of scientific study of Alzheimer's disease, a disease of catastrophic proportions whose symptoms include serious forgetfulness; changes in personality; confused, restless, and irritable behavior; and problems with judgment, concentration, writing, reading, speech, and naming of objects. It discusses…

  17. 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...

  18. Differing astrocytic cytoskeleton alterations in alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Olabarria, M.; Noristani, H.; Chvátal, Alexandr; Verkhratsky, Alexei; Rodríguez Arellano, Jose Julio

    2009-01-01

    Roč. 57, č. 13 (2009), S103-S104. ISSN 0894-1491. [European Meeting on Glial Cells in Health and Disease /9./. 09.09.2009-12.09.2009, Paris] Institutional research plan: CEZ:AV0Z50390703 Keywords : Alzheimer ´s disease Subject RIV: FH - Neurology

  19. Differences of neuroimaging between early-onset and late-onset alzheimer-type dementia

    International Nuclear Information System (INIS)

    Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer's disease (EAD) differ from those of late-onset Alzheimer's disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT (e.g. global hypoperfusion in addition to temporoparietal change) than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations. (author)

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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

  5. Role of physical exercise in Alzheimer's disease

    OpenAIRE

    Chen, Wei-Wei; Zhang, Xia; HUANG, WEN-JUAN

    2016-01-01

    The benefits of physical exercise on the brain and general wellness are well recognised, but not particularly well known to the general public. Understanding the importance of integrating active behavior for overall health is crucial at any age and particularly for the elderly who are at risk of developing Alzheimer's disease (AD), a disease mainly affecting individuals aged >65 years. AD is a neurodegenerative disease characterized by extracellular senile plaques of amyloid-β, intracellular ...

  6. Alzheimer's Disease: Genes, pathogenesis and risk prediction

    OpenAIRE

    Sleegers, Kristel; Duijn, Cock

    2001-01-01

    textabstractWith the aging of western society the contribution to morbidity of diseases of the elderly, such as dementia, will increase exponentially. Thorough preventative and curative strategies are needed to constrain the increasing prevalence of these disabling diseases. Better understanding of the pathogenesis of disease will enable development of therapy, prevention and the identification of high-risk groups in the population. Here, we review the genetic epidemiology of Alzheimer's dise...

  7. Alzheimer's Disease and Stem Cell Therapy

    OpenAIRE

    Choi, Sung S.; Lee, Sang-Rae; Kim, Seung U.; Lee, Hong J.

    2014-01-01

    The loss of neuronal cells in the central nervous system may occur in many neurodegenerative diseases. Alzheimer's disease is a common senile disease in people over 65 years, and it causes impairment characterized by the decline of mental function, including memory loss and cognitive impairment, and affects the quality of life of patients. However, the current therapeutic strategies against AD are only to relieve symptoms, but not to cure it. Because there are only a few therapeutic strategie...

  8. Physiological genomics analysis for Alzheimer's disease.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2013-01-01

    Alzheimer's disease is a common kind of dementia. This disorder can be detected in all countries around the world. This neurological disorder affects millions of population and becomes an important concern in modern neurology. There are many researches on the pathogenesis of Alzheimer's disease. Although it has been determined for a long time, there is no clear-cut that this is a case with genetic disorder or not. A physiological genomics is a new application that is useful for track function to genes within the human genome and can be applied for answering the problem of underlying pathobiology of complex diseases. The physiogenomics can be helpful for study of systemic approach on the pathophysiology, and genomics might provide useful information to better understand the pathogenesis of Alzheimer's disease. The present advent in genomics technique makes it possible to trace for the underlying genomics of disease. In this work, physiological genomics analysis for Alzheimer's disease was performed. The standard published technique is used for assessment. According to this work, there are 20 identified physiogenomics relationship on several chromosomes. Considering the results, the HADH2 gene on chromosome X, APBA1 gene on chromosome 9, AGER gene on chromosome 6, GSK3B gene on chromosome 3, CDKHR1 gene on chromosome 17, APPBP1 gene on chromosome 16, APBA2 gene on chromosome 15, GAL gene on chromosome 11, and APLP2 gene on chromosome 11 have the highest physiogenomics score (9.26) while the CASP3 gene on chromosome 4 and the SNCA gene on chromosome 4 have the lowest physiogenomics score (7.44). The results from this study confirm that Alzheimer's disease has a polygenomic origin. PMID:23661967

  9. 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.

  10. 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...

  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. 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.

  13. 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

  14. 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 '

  15. Next generation therapeutics for Alzheimer's disease

    OpenAIRE

    Bredesen, Dale E.; John, Varghese

    2013-01-01

    To date, no truly effective therapy has been developed for Alzheimer's disease or mild cognitive impairment. In searching for new approaches that may succeed where previous ones have failed, it may be instructive to consider the successful therapeutic developments for other chronic illnesses such as cancer and human immunodeficiency virus.

  16. Association studies in late onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Goate, A.M.; Lendon, C.; Talbot, C. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  17. Why Do We Get Alzheimer's Disease?

    International Nuclear Information System (INIS)

    Neurodegenerative diseases and Alzheimer's disease (AD) in particular, are among the major health concerns of the elderly in industrialized societies. The cause of AD is unknown and no disease-modifying treatments are available. The disease is characterized clinically by a progressive dementia and pathologically by the accumulation of protein aggregates in the brain and a profound loss of nerve cells. It has also become clear recently that local immune responses are activated in the AD brain and may have a role in the disease. Our laboratory uses genetic mouse models to understand the disease process and to identify potential therapeutic targets.

  18. 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) ...

  19. 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...

  20. Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... interventions designed to lower the levels of Alzheimer's pathologies in the brain treatments for health issues that may be linked to Alzheimer's, such as heart disease and type 2 diabetes cognitive training eating ...

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

    Medline Plus

    Full Text Available ... the risk of developing Alzheimer's disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's and related brain disorders As we learn more, researchers move ever ...

  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. 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...

  4. Increased hippocampal neurogenesis in Alzheimer's disease

    OpenAIRE

    Jin, Kunlin; Peel, Alyson L.; Mao, Xiao Ou; Xie, Lin; Cottrell, Barbara A.; Henshall, David C.; Greenberg, David A.

    2003-01-01

    Neurogenesis, which persists in the adult mammalian brain, may provide a basis for neuronal replacement therapy in neurodegenerative diseases like Alzheimer's disease (AD). Neurogenesis is increased in certain acute neurological disorders, such as ischemia and epilepsy, but the effect of more chronic neurodegenerations is uncertain, and some animal models of AD show impaired neurogenesis. To determine how neurogenesis is affected in the brains of patients with AD, we investigated the expressi...

  5. SPECT in Alzheimer`s disease and the dementias

    Energy Technology Data Exchange (ETDEWEB)

    Bonte, F.J. [Univ. of Texas Southwestern Medical Center, Dallas (United States)

    1991-12-31

    Among 90 patients with a clinical diagnosis of Alzheimer`s disease (AD), two subgroups were identified for special study, including 42 patients who had a history of dementia in one or more first-degree relatives, and 14 who had a diagnosis of early AD. Of the 42 patients with a family history of dementia, 34 out of the 35 patients whose final clinical diagnosis was possible or probable AD had positive SPECT rCBF studies. Studies in the 14 patients thought to have very early AD were positive in 11 cases. This finding suggests that altered cortical physiology, and hence, rCBF, occurs quite early in the course of AD, perhaps before the onset of symptoms. It is possible that Xenon 133 rCBF studies might be used to detect the presence of subclinical AD in a population of individuals at risk to this disorder. Despite the drawbacks of a radionuclide with poor photon energy, Xenon 133, with its low cost and round-the-clock availability, deserves further study. Although the physical characteristics of Xenon 127 might make it preferable as a SPECT tracer, it is still not regularly available, and some instrument systems are not designed to handle its higher photon energies.

  6. 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

  7. An Investigation of the Late Excitatory Potentials in the Hand following Transcranial Magnetic Stimulation in Early Alzheimer's Disease.

    OpenAIRE

    Balla, christina; Pepin, Jean-Louis; Maertens de Noordhout, Alain

    2014-01-01

    BACKGROUND: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). PATIENTS AND METHODS: We measured the silent period (SP) induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. RESULTS: An increase in the duration of the...

  8. 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 ...

  9. Screening for new agonists against Alzheimer's disease.

    Science.gov (United States)

    Zheng, Huiqin; Wei, Dong-Qing; Zhang, Rui; Wang, Chunfang; Wei, Huachun; Chou, Kuo-Chen

    2007-09-01

    To find new drug candidates for treating Alzheimer's disease, we used the similarity search technique and GTS-21 as a template to search the Traditional Chinese Medicines Database. The high-score molecules thus obtained were compared with the template through the flexible alignment. Those molecules which had good alignment with GTS-21 were selected for conducting the docking studies aimed at the alpha7 nicotinic acetylcholine receptor. The CHARMM22 force field was taken to compute the partial charge and the TABU search was adopted to operate the docking process. The docking results thus obtained were used to compare with that of GTS-21. Those molecules which had better docking results than that of GTS-21 were singled out for further consideration. Finally, it was found through an in-depth structural analysis that Mol 7235 might be a promising candidate for further modification by experiments to make it become an effective drug for treating Alzheimer's disease. PMID:17897076

  10. 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.

  11. 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)

  12. Atrophy and magnetization transfer ratio of the corpus callosum in patients with Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Imon, Yukari; Hanyu, Haruo; Iwamoto, Toshihiko; Takasaki, Masaru; Abe, Kimihiko [Tokyo Medical Coll. (Japan)

    1998-12-01

    We compared atrophy and magnetization transfer ratio (MTR) in the corpus callosum in patients with Alzheimer`s disease and age-matched normal subjects. Fifteen patients with Alzheimer`s disease and fourteen normal subjects received MRI. The corpus callosum was divided into three parts (anterior, middle, and posterior portions) on midsagittal slice, and their areas on T2-weighted reversed images and MTR on magnetization transfer contrast images in each portion were measured. The area and MTR decreased significantly in the posterior portion in patients with Alzheimer`s disease. In the anterior portion, MTR decreased significantly, but although the area showed no significant change. In the middle portion, the area and MTR showed no significant change. MTR and the area was correlated in each portion in patients with Alzheimer`s disease. The score of Hasegawa dementia scale-revised (HDS-R) and the area of the middle, posterior and total of corpus callosum were significantly related. The score of HDS-R and MTR in the anterior portion of corpus callosum were significantly related. The present study revealed decreases in MTR in the anterior portion of the corpus callosum of patients with Alzheimer`s disease although the area showed no significant change, and this change suggests the increase in free water and/or the decrease in bound water in tissues, probably due to demyelination and axonal degeneration. (author)

  13. Ayurvedic medicinal plants for Alzheimer's disease: a review

    OpenAIRE

    Rao, Rammohan V.; Descamps, Olivier,; John, Varghese; Bredesen, Dale E.

    2012-01-01

    Alzheimer's disease is an age-associated, irreversible, progressive neurodegenerative disease that is characterized by severe memory loss, unusual behavior, personality changes, and a decline in cognitive function. No cure for Alzheimer's exists, and the drugs currently available to treat the disease have limited effectiveness. It is believed that therapeutic intervention that could postpone the onset or progression of Alzheimer's disease would dramatically reduce the number of cases in the n...

  14. Practical Principles for the Management of Alzheimer's Disease

    OpenAIRE

    Christensen, Daniel D.

    2002-01-01

    Alzheimer's disease is a complex disorder that is particularly challenging to treat and manage. Early recognition of Alzheimer's disease is the first step toward providing patients with optimal therapy and the best opportunity for treatment response. Subsequently, physicians will need to address issues that emerge as the disease inevitably progresses. As the number of elderly patients with Alzheimer's disease increases, it becomes increasingly important for the primary care physician—usually ...

  15. 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....

  16. 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...

  17. 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...

  18. Psychotherapy for individuals with Alzheimer disease.

    Science.gov (United States)

    Bonder, B R

    1994-01-01

    Individuals with Alzheimer disease often experience depression, anger, and other psychological symptoms. Various forms of psychotherapy have been attempted with these individuals, including insight oriented therapy and less verbal therapies such as music therapy and art therapy. Although there are few data-based outcome studies that support the effectiveness of these interventions, case studies and descriptive information suggest that they can be helpful in alleviating negative emotions and minimizing problematic behaviors. PMID:7999349

  19. Neuroprotective peptides related to Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Slaninová, Jiřina; Borovičková, Lenka; Bláha, I.; Hlaváček, Jan; Krejčová, G.; Patočka, J.

    Patras : Typorama, 2005 - (Cordopatis, P.; Manessi-Zoupa, E.; Pairas, G.), 147-154 ISBN 960-7620-31-3. [Hellenic Forum on Bioactive Peptides /4./. Patras (GR), 22.04.2004-24.04.2004] R&D Projects: GA ČR(CZ) GA305/03/1100 Institutional research plan: CEZ:AV0Z40550506 Keywords : peptides * Alzheimer's disease * humanin Subject RIV: CE - Biochemistry

  20. Neurogenesis in Alzheimer´s disease

    Czech Academy of Sciences Publication Activity Database

    Rodríguez Arellano, Jose Julio; Verkhratsky, Alexei

    2011-01-01

    Roč. 219, č. 1 (2011), s. 78-89. ISSN 0021-8782 R&D Projects: GA ČR GA309/09/1696; GA ČR(CZ) GAP304/11/0184; GA ČR GA309/08/1381; GA ČR GA305/08/1384 Institutional research plan: CEZ:AV0Z50390703 Keywords : Alzheimer 's disease * hippocampus * neurodegeneration Subject RIV: FH - Neurology Impact factor: 2.370, year: 2011

  1. Diagnosis and management of Alzheimer's disease

    OpenAIRE

    Burns, Alistair

    2000-01-01

    The diagnosis of Alzheimer's disease (AD) is a 2-stage process, in stage 1, the dementia syndrome, comprising neuropsychologic and neuropsychiatrie components together with deficits in activities of daily living, is differentiated on clinical grounds from a number of other conditions (delirium, concomitant physical illness, drug treatment normal memory loss, etc), in stage 2, the cause is determined, AD being the most common, followed by vascular dementia, Lewy-body dementia, frontal lobe dem...

  2. Amyloid β protein and Alzheimer disease

    OpenAIRE

    Square, D

    1997-01-01

    Amyloid beta protein is predominant in senile plaques, the neuropathologic hallmarks of Alzheimer disease. Researchers in Winnipeg have shown that this protein can overstimulate certain hydrolytic enzymes to break down the phospholipid building blocks of the brain-cell wall. They speculate that the abnormal destruction of phospholipids gradually drains the energy resources a neuron uses to rebuild its membrane. As neurons "burn out," the brain loses its ability to function normally. In view o...

  3. 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

  4. 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....

  5. 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 ...

  6. 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...

  7. 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

  8. 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...

  9. Management of Alzheimer's Disease: Defining the Role of Donepezil

    OpenAIRE

    Tim Ibbotson; Karen L. Goa

    2002-01-01

    Alzheimer's disease affects 15 million people worldwide. As the elderly population grows, the incidence of Alzheimer's disease will also increase. It is estimated that by 2010, 40 million US citizens will be over the age of 65 years and by 2040, it is predicted that 14 million US citizens will have Alzheimer's disease. There is currently no treatment which stops or delays the progression of this condition; however, anticholinesterase therapy provides some symptomatic relief. The cognitive imp...

  10. 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

  11. Neuroimage in neuroecthodermic diseases Part II: Tuberous Sclerosis

    International Nuclear Information System (INIS)

    A prospective clinicoradiological study has been carried out in 36 patients with tuberous sclerosis. The neuroimaging studies detected some type of disorder in 94% of patients, contributing significantly to the positive diagnosis of the disease. CT was better for viewing periventricular nodules, while MR was more reliable in disclosing the number and location of cortical and white matter lesions. The use of gadolinium-DTPA in MR demonstrated frequent uptake by the periventricular nodules which was exceptional in the cortical and subcortical lesions. The use of contrast, both in CT and in MR, enhanced the images of the 7 presumed giant-cell astrocytomas detected in 6 patients. Uptake by the tumors was always much greater than that observed in the nodules, being and important criterion for the differentiation between nodules and small tumors. The appearance and topography of these CNS lesions can be reasonably well explained by considering the disease to be a disorder of the migration of dysgenic cells. We have found no consistent correlation between the neuroradiological findings and the clinical evolution of the patients. MR and CT are similarly useful in the diagnosis of tuberous sclerosis. Given that MR is more effective in the detection of the set of intracranial lesions, it could be used as the initial technique, resorting to CT in those cases in which the clinical evidence is highly suggestive and the MR study is negative. Periodic MR control is not justified unless there is suspicion of tumor implantation or growth

  12. 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.

  13. 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 the brain to function well. Alzheimer's disease ...

  14. 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....

  15. In vivo amyloid imaging in Alzheimer's disease

    International Nuclear Information System (INIS)

    Targeted approaches to therapy for Alzheimer's disease have evolved based on detailed understanding of the genetic, molecular biologic, and neuropathologic basis of the disease. Given the potential for greater treatment efficacy in the earlier stages of the disease, the notion of early diagnosis has become more relevant. Current clinical and imaging diagnostic approaches lack reliability in the preclinical and prodromal phases of the disease. We review emerging studies on imaging of the molecular substrate of the disease, most notably the amyloid peptide, which hope to increase early diagnostic efficacy. We offer a brief overview of the demographics, diagnostic criteria, and current imaging tests, followed by a review of amyloid biology and developments in cerebral amyloid imaging yielded by recent in vitro, in vivo and human studies. (orig.)

  16. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H. [Huddinge Hospital, Karolinska Institute, Dept. of Geriatric Medicine, (Sweden); Houlden, H.; Rossor, M. [St. Mary`s Hospital, Dept. of Neurology, Medical School, London (United Kingdom); Hardy, J. [University of South Florida, Suncoast Alzheimer`s Disease Research Labs, Department of Psychiatry, Tampa (United States)

    1995-02-01

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer`s disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer`s disease families, as it is closely linked to the gene. Most cases of Alzheimer`s disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer`s disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.).

  17. [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 consumption of fish, vegetables, and low glycemic index fruits; a moderate amount of meat and dairy products; and a lower amount of carbohydrates and refined sugar. PMID:27395465

  18. Improving Alzheimer's disease diagnosis with machine learning techniques.

    Science.gov (United States)

    Trambaiolli, Lucas R; Lorena, Ana C; Fraga, Francisco J; Kanda, Paulo A M; Anghinah, Renato; Nitrini, Ricardo

    2011-07-01

    There is not a specific test to diagnose Alzheimer's disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity. PMID:21870467

  19. 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)

  20. 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.

  1. 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

  2. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... throughout the brain and most areas of the brain have shrunk (above right). Understanding Alzheimer's–Free Videos Can Help The NIHSeniorHealth ... spinal fluid, to track subtle changes in the brain before symptoms appear ... NIA Alzheimer's Disease Education and Referral (ADEAR) Center at 1-800-438- ...

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

    DEFF Research Database (Denmark)

    Waldorff, F B; Buss, D V; Eckermann, A; Rasmussen, M L H; Keiding, Niels; Rishøj, S; Siersma, Volkert; Sørensen, J; Sørensen, L V; Vogel, A; Waldemar, G

    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....

  4. 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)

  5. 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…

  6. 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....

  7. 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…

  8. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012

    Science.gov (United States)

    2012-11-06

    ... thirty-seventh. (Presidential Sig.) [FR Doc. 2012-27196 Filed 11-5-12; 8:45 am] Billing code 3295-F3 ... 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...

  9. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

    Science.gov (United States)

    2011-11-04

    ... United States of America the two hundred and thirty-sixth. (Presidential Sig.) [FR Doc. 2011-28840 Filed... 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...

  10. 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…

  11. 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)

  12. Diminished glucose transport and phosphorylation in Alzheimer`s disease determined by dynamic FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Piert, M.; Koeppe, R.A.; Giordani, B.; Berent, S.; Kuhl, D.E. [Univ. of Michigan Medical Center, Ann Arbor, MI (United States)

    1996-02-01

    Using dynamic [{sup 18}F] fluorodeoxyglucose (FDG) and PET, kinetic rate constants that describe influx (K{sub 1}) and efflux (k{sub 2}) of FDG as well s phosphorylation (k{sub 3}) and dephosphorylation (k{sub 4}) were determined in patients with probable Alzheimer`s disease and similarly aged normal controls. The regional cerebral metabolic rate for glucose (CMR{sub glu}) was calculated from individually fitted rate constants in frontal, temporal, parietal and occipital cerebral cortex, caudate nucleus, putamen, thalamus and cerebellar cortex. Dynamic PET scans were obtained in normal controls (n = 10, mean age = 67) and Alzheimer`s disease patients (n = 8, mean age = 67) for 60 min following injection of 10 mCi of FDG. The Alzheimer`s disease group was characterized by decreases of the CMR{sub glu} ranging from 13.3% in the frontal to 40.9% in the parietal cortex, which achieved significance in all regions except the thalamus. K{sub 1} was significantly reduced in the parietal (p < 0.01) and temporal cortices (p < 0.005), temporal and occipital cortex, and in the putamen and cerebellum (p < 0.05). The rate constants k{sub 2} and k{sub 4} were unchanged in the Alzheimer`s disease group. These data suggest that hypometabolism in Alzheimer`s disease is related to reduced glucose phosphorylation activity as well as diminished glucose transport, particularly in the most metabolically affected areas of the brain, the parietal and temporal cortex. 60 refs., 2 figs., 2 tabs.

  13. Who Would Take Care of the Person with Alzheimer's Disease If Something Happened to You?

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  14. Home Safety for People with Alzheimer's Disease: Home Safety Room by Room

    Science.gov (United States)

    ... Referral Center Alzheimer's Disease Education and Referral Center Alzheimer's Disease Education and Referral Center Home About Alzheimer’s Alzheimer's Basics Causes Symptoms Diagnosis Treatment Caregiving Other Dementias Publications FAQs ...

  15. 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

  16. 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 ...

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

    DEFF Research Database (Denmark)

    Lopez, Oscar L; Schwam, Elias; Cummings, Jeffrey; Gauthier, Serge; Jones, Roy; Wilkinson, David; Waldemar, Gunhild; Zhang, Richard; Schindler, Rachel

    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....

  18. 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 ... Alzheimer's disease as the brain and body age? Scientific research is helping to unravel the mystery of ...

  19. 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 ...

  20. 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,...

  1. 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....

  2. 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

  3. 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 ...

  4. 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.)

  5. 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.)

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    Science.gov (United States)

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  11. 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

  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. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    International Nuclear Information System (INIS)

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOEε4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the ε4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single ε4 allele. On the contrary the relation of ε4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping

  15. 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

  16. 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

  17. Regional metabolism: associations with dyscalculia in Alzheimer's disease

    OpenAIRE

    Hirono, N.; Mori, E.; Ishii, K.; T. Imamura; Shimomura, T.; Tanimukai, S.; H. Kazui; Hashimoto, M; Yamashita, H; Sasaki, M

    1998-01-01

    OBJECTIVES—The ability to calculate, which is an important aspect of social daily living, is commonly impaired in patients with Alzheimer's disease even early in the course of the disease. Dyscalculia is often accompanied by focal brain damage, and has been argued to be an independent sign localised around the left temporoparietal region. However, the region most responsible for dyscalculia in Alzheimer's disease has not been determined. The relation between calculation a...

  18. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    Science.gov (United States)

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. PMID:27079753

  19. Medical disorders in Alzheimer's disease and vascular dementia.

    OpenAIRE

    Förstl, H.; Cairns, N.; Burns, A.; Luthert, P.

    1991-01-01

    The clinical and postmortem findings of 29 patients with Alzheimer's disease were evaluated and compared to the findings of 19 patients with vascular dementia. The patients with Alzheimer's disease had received treatment for an average of 2.0 internal medical disorders, the patients with vascular dementia for 2.1 disorders. The average number of medical diseases found at postmortem was 3.7 in the group with Alzheimer's dementia and 4.1 in vascular dementia. Apart from a marginally increased r...

  20. 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

  1. Randomized controlled trials for Alzheimer disease and Parkinson disease.

    Science.gov (United States)

    Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

    2016-01-01

    The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients. PMID:27100346

  2. Astrocytes in physiological aging and Alzheimer's disease.

    Science.gov (United States)

    Rodríguez-Arellano, J J; Parpura, V; Zorec, R; Verkhratsky, A

    2016-05-26

    Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits in reactivity coincide with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at the prevention and cure of neurodegenerative disorders. PMID:25595973

  3. Alzheimer disease pathology as a host response.

    Science.gov (United States)

    Castellani, Rudy J; Lee, Hyoung-Gon; Zhu, Xiongwei; Perry, George; Smith, Mark A

    2008-06-01

    Identification of amyloid-beta and tau as the major protein components of senile plaques and neurofibrillary tangles, respectively, led to an exponential increase in investigations of these proteins and their corresponding metabolic pathways in Alzheimer disease (AD). The presumptions inherent in most studies and in the dogma of the amyloid cascade concept are that these hallmark lesions in AD brains contain molecules that drive the disease process, and that the proteinaceous accumulations are themselves toxic. On the other hand, the lesions of AD are, by definition, end-stage, and their relationship to the clinical disease is inconsistent; this has long been known but, generally, has not been acknowledged until relatively recently. Some recent attempts to address the etiology and pathogenesis of AD discard the pathology and focus on the interplay between invisible toxic intermediates, that is, amyloid-beta oligomers and the synapse. The concept that the hallmark lesions may be nontoxic (something we have long suggested) is slowly gaining acceptance. We favor the interpretation that senile plaques and neurofibrillary tangles represent a host response to an upstream pathophysiologic process, and that the therapeutic targeting of lesions, including toxic intermediates, will succeed only in the event that the host response is directly deleterious. Therefore, renewed efforts aimed at elucidating fundamental age-related processes such as oxidative stress and/or inflammatory mediators are warranted. PMID:18520771

  4. Cholinesterase inhibitors: cardioprotection in Alzheimer's disease.

    Science.gov (United States)

    Monacelli, Fiammetta; Rosa, Gianmarco

    2014-01-01

    Alzheimer's disease is a life shortening disease, and the lack of disease modifying therapy implies a huge impact on life expectancy as well as an outgrowing financial and socioeconomic burden. Cholinesterase inhibitors (ChEIs) represent the first line symptomatic therapy, whose benefit to harm ratio is still a matter of debate. Acetylcholinesterase enzyme is a core interest for pharmacological and toxicological research to unmask the fine balance between therapeutic drug efficacy, tolerability, safety, and detrimental effects up to adverse drug reaction. So far, a body of evidence advocated that an increased vagal tone was associated to an increased risk of gastrointestinal and cardiac side effects (negative chronotropic, arrhytmogenic, hypotensive effects), able to hamper ChEIs effects on cognition, reducing administration feasibility and compliance, especially in older and comorbid patients. Conversely, a growing body of evidence is indicating a protective role of ChEIs on overall cardiovascular mortality in patients with dementia, through a series of in vitro and in vivo investigations. The present review is aimed to report the up to date literature in the controversial field of ChEIs and cardioprotection in dementia, offering a state of the art, which may constitute the conceptual framework to be enlarged in order to build higher evidence. Chronic vagal nerve stimulation acted upon by donepezil might improve long term survival through pharmacological properties apart from cholinesterase inhibition, able to offer cardioprotection, abating the overall cardiovascular risk, and, thus profiling a new line of therapeutic intervention for ChEI drug class. PMID:25024324

  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. 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...

  7. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M. [and others

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  8. 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 ...

  9. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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 ...

  15. 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 ...

  16. 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 ...

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

    Medline Plus

    Full Text Available ... changes that take place in Alzheimer's disease. Abnormal structures called beta amyloid plaques and neurofibrillary tangles are ... is modified. In normal brain cells, tau stabilizes structures critical to the cell's internal transport system. Nutrients ...

  18. 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

  19. 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 ...

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

    Medline Plus

    Full Text Available ... tau separates from the microtubules, causing them to fall apart. Strands of this tau combine to form ... disease as the brain and body age? Scientific research is helping to unravel the mystery of Alzheimer's ...

  1. Treatment Guidelines for Alzheimer's Disease: Redefining Perceptions in Primary Care

    OpenAIRE

    Geldmacher, David S

    2007-01-01

    Background: Current treatment guidelines for Alzheimer's disease (AD) do not reflect more recently collected data on therapeutic outcomes other than cognitive function and memory, and this has led to a limited understanding of the value of drug therapy in AD.

  2. Cardiovascular risk and hippocampal thickness in Alzheimer's disease.

    Science.gov (United States)

    Donix, Markus; Scharf, Maria; Marschner, Kira; Werner, Annett; Sauer, Cathrin; Gerner, Antje; Nees, Josef A; Meyer, Shirin; Donix, Katharina L; Von Kummer, Rüdiger; Holthoff, Vjera A

    2013-01-01

    Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease. PMID:24228185

  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. Diagnosis and treatment of Alzheimer`s disease; Diagnostik und Therapie der Demenz vom Alzheimer-Typ

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J. [Muenchen Univ. (Germany). Psychiatrische Klinik und Poliklinik

    1997-09-05

    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) [Deutsch] Die Alzheimer-Demenz kann heute mit grosser Sicherheit auch in der hausaerztlichen Praxis festgestellt werden. Dennoch werden Hirnleistungsstoerungen meist erst spaet im Krankheitsverlauf diagnostiziert. Oft bestehen dann bereits fortgeschrittene kognitive Beeintraechtigungen, die zu schweren psychosozialen und oekonomischen Belastungen innerhalb von Familie und Gesellschaft fuehren. Es sind mehr als 50 Erkrankungen beschrieben, die eine Demenz verursachen koennen. Die Alzheimer-Demenz macht davon den groessten Anteil aus und wirft durch ihre zunehmende Haeufigkeit erhebliche medizinische, pflegerische und soziooekonomische Probleme auf. Die weiterhin ungeklaerte Aetiologie ist eine der grossen Herausforderungen der neurobiologischen Grundlagenforschung. Aktuelle klinische Therapiestudien mit Acetylcholinesterase-Hemmern konnten ihre Wirksamkeit auf die kognitive Kernsymptomatik bei leichten und mittelgradig dementiellen Syndromen nachweisen. Durch ein dynamisches Konzept der multidisziplinaeren Diagnostik im Zusammenschluss zwischen spezialisierten Gedaechtnisambulanzen, klinisch-psychogeriatrischen Abteilungen und niedergelassenen Allgemein- und Fachaerzten kann eine optimierte Frueh- und Differentialdiagnostik bei Demenz-Patienten erfolgen. Dies erlaubt eine rechtzeitige individuelle Lebens- und Pflegeplanung fuer Alzheimer-Patienten und

  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. Alzheimer disease immunotherapeutics: then and now.

    Science.gov (United States)

    Jindal, Harashish; Bhatt, Bhumika; Sk, Shashikantha; Singh Malik, Jagbir

    2014-01-01

    Dementia is a public health priority and one of the major contributors to morbidity and global non-communicable disease burden, thus necessitating the need for significant health-care interventions. Alzheimer disease (AD) is the most common cause of dementia and may contribute to 60-70% of cases. The cause and progression of AD are not well understood but have been thought to be due at least in part to protein misfolding (proteopathy) manifest as plaque accumulation of abnormally folded β-amyloid and tau proteins in brain. There are about 8 million new cases per year. The total number of people with dementia is projected to almost double every 20 years, to 66 million in 2030 and 115 million in 2050. Immunotherapy in AD aimed at β-amyloid covers 2 types of vaccination: active vaccination against Aβ42 in which patients receive injections of the antigen itself, or passive vaccination in which patients receive injections of monoclonal antibodies (mAb) against Aβ42. Three of the peptide vaccines for active immunizations, CAD106, ACC001, and Affitope, are in phase 2 clinical trials. Three of the mAbs solanezumab, gantenerumab, and crenezumab, are or were in phase 2 and 3 clinical studies. While the phase 3 trials failed, one of these may have shown a benefit at least in mild forms of AD. There is a need for a greater initiative in the development of immunotherapeutics. Several avenues have been explored and still to come. PMID:25483498

  7. Origins of delusions in Alzheimer's disease.

    Science.gov (United States)

    Reeves, Suzanne J; Gould, Rebecca L; Powell, John F; Howard, Robert J

    2012-11-01

    Research over the past two decades supports a shared aetiology for delusions in Alzheimer's disease (AD) and schizophrenia. Functional networks involved in salience attribution and belief evaluation have been implicated in the two conditions, and striatal D2/3 receptors are increased to a comparable extent. Executive/frontal deficits are common to both disorders and predict emergent symptoms. Putative risk genes for schizophrenia, which may modify the AD process, have been more strongly implicated in delusions than those directly linked with late-onset AD. Phenotypic correlates of delusions in AD may be dependent upon delusional subtype. Persecutory delusions occur early in the disease and are associated with neurochemical and neuropathological changes in frontostriatal circuits. In contrast, misidentification delusions are associated with greater global cognitive deficits and advanced limbic pathology. It is unclear whether the two subtypes are phenomenologically and biologically distinct or are part of a continuum, in which misidentification delusions manifest increasingly as the pathological process extends. This has treatment implications, particularly if they are found to have discrete chemical and/or pathological markers. PMID:22910677

  8. Alzheimer's Disease: A Healthcare Burden of Epidemic Proportion

    OpenAIRE

    Dharmarajan, T.S.; Gunturu, Srinivas G.

    2009-01-01

    Alzheimer's disease is the most common cause of dementia and increases in prevalence exponentially with age, with trends in the United States likely to worsen in ensuing decades. The pathology in Alzheimer's disease is characterized by an increase in extracellular amyloid plaques and intraneural neurofibrillary tangles, with neuronal destruction in several areas of the brain, and biochemically by a deficiency in acetylcholine; clinical manifestations include progressive loss of memory, change...

  9. 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.)

  10. 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...

  11. 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....

  12. 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...

  13. Cerebral correlates of psychotic symptoms in Alzheimer's disease

    OpenAIRE

    Mega, M; L. Lee; 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 equ...

  14. 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...

  15. 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

  16. 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

  17. 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'. PMID:26025658

  18. Analysis of genetics and risk factors of Alzheimer's Disease.

    Science.gov (United States)

    Panpalli Ates, M; Karaman, Y; Guntekin, S; Ergun, M A

    2016-06-14

    Alzheimer's Disease is the leading neurodegenerative cause of dementia. The pathogenesis is not clearly understood yet, is believed to be the complex interaction between genetic and environmental factors. Consequently vascular risk factors and Apolipoprotein E genotyping are increasingly gaining importance. This study aimed at assessing the relationships between Alzheimer's Disease and Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with "possible Alzheimer's Disease" in the Gazi University, Department of Neurology, were included in the study and age-matched volunteer patients who attended the polyclinic were included as a control group. In this study, the risk factors including low education level, smoking, hyperlipidemia, higher serum total cholesterol levels, and hyperhomocysteinemia were found to be statistically significantly more common in the Alzheimer's Disease group in comparison to the Control Group, while all Apolipoprotein E ε4/ε4 genotypes were found in the Alzheimer's Disease group. The presence of the Apolipoprotein E ε4 allele is believed to increase vascular risk factors as well as to affect Alzheimer's Disease directly. The biological indicators which are used in identifying the patients' genes will be probably used in the treatment plan of the patients in the future. PMID:27026590

  19. 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.

  20. Copper Chelation in Alzheimer's Disease Protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2013-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder affecting millions of people in the U.S. AD is primarily characterized at the cellular level by densely tangled fibrils of amyloid- β protein. These protein clusters have been found in association with elevated levels of multiple transition metals, with copper being the most egregious. Interestingly, metal chelation has shown promise in attenuating the symptoms of AD in recent clinical studies. We investigate this process by constructing an atomistic model of the amyloid- β-copper complex and profile the energetic viability in each of its subsequent disassociation stages. Our results indicate that five energetic barriers must be overcome for full metal chelation. The energy barriers are biologically viable in the presence water mediated bond and proton transfer between the metal and the protein. We model the chelation reaction using a consecutive path nudged elastic band method implemented in our ab initio real-space multi-grid code to obtain a viable sequence. This reaction model details a physically consistent explanation of the chelation process that could lead to the discovery of more effective chelation agents in the treatment of AD.

  1. Microglia in Alzheimer's disease: A multifaceted relationship.

    Science.gov (United States)

    ElAli, Ayman; Rivest, Serge

    2016-07-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting elderly people worldwide, which is mainly characterized by cerebral amyloid-beta (Aβ) plaque deposition and neurofibrillary tangle formation. The interest in microglia arose from the overwhelming experimental evidence that outlined a key role of neuroinflammation in AD pathology. Microglia constitute the powerhouse of the innate immune system in the brain. It is now widely accepted that microglia are myeloid-derived cells that infiltrate the developing brain at the early embryonic stages, and acquire a highly ramified phenotype postnatally. Microglia use these dynamic ramifications as sentinels to sense and detect any occurring alteration in brain homeostasis. Once a danger signal is detected, microglia get activated by acquiring a less ramified phenotype, and mount adequate responses that range from phagocyting cell debris to secreting inflammatory and trophic factors. Earlier reports have demonstrated, unequivocally, that microglia surround Aβ plaques and internalize Aβ microaggregates. However, the implication of these observations in AD pathology, and consequently treatment, is still a matter of debate. Nonetheless, targeting the activity of these cells constituted a convergent point in this debate. Unfortunately, the conflicting experimental findings obtained following the modulation of microglial activity in AD, further fueled the debate. This review aims at providing an overview regarding what we know about the implication of microglia in AD pathology, and treatment. The emerging role of monocytes is also discussed. PMID:26254232

  2. [Immunotherapy for Alzheimer's disease targeting Aβ].

    Science.gov (United States)

    Tabira, Takeshi

    2016-03-01

    Active and passive immunization of Alzheimer model mice with Aβ showed clearance of aggregated amyloid β deposits and improved memory and learning. Although human trial was halted because of autoimmune encephalitis, the trial revealed that immunization with Aβ also deleted amyloid deposits in humans without clinical benefit. On these proof of concept, several clinical trials using monoclonal antibodies are on-going. Although solanezumab which recognizes Aβ monomer turned out ineffective in the primary endpoint, it showed significant beneficial effect in mild AD cases in the secondary outcome. Solanezumab is now on a large scale phase III trial in mild AD cases in the world. If it turns out to be effective, it will be the first disease modifying drug for AD in a few years. However, since monoclonal antibodies are extremely expensive, less expensive and long acting active immunization will be widely accepted. More effective and sophisticated vaccines such as DNA vaccine and recombinant viral vaccines will be utilized in future. PMID:27025080

  3. 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

  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. 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.)

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Functional Neuroimaging of Motor Control inParkinson’s Disease

    DEFF Research Database (Denmark)

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

    2014-01-01

    denervation affects neural processing in the denervated striatal motor territory. In contrast, fronto-parietal motor areas display both increases as well as decreases in movement related activation. This points to a more complex relationship between altered cortical physiology and nigrostriatal dopaminergic...... and yielded consistent alterations in neural activity in patients with PD. Differences in cortical activation between PD patients and healthy controls converged in a left-lateralized fronto-parietal network comprising the presupplementary motor area, primary motor cortex, inferior parietal cortex, and...... posterior motor putamen, which improved with dopaminergic medication. The likelihood of detecting a decrease in putaminal activity increased with motor impairment. This reduced motor activation of the posterior putamen across previous neuroimaging studies indicates that nigrostriatal dopaminergic...

  11. Metabolic profiling distinguishes three subtypes of Alzheimer's disease.

    Science.gov (United States)

    Bredesen, Dale E

    2015-08-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

  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. Homonymous Hemianopsia Associated with Probable Alzheimer's Disease.

    Science.gov (United States)

    Ishiwata, Akiko; Kimura, Kazumi

    2016-01-01

    Posterior cortical atrophy (PCA) is a rare neurodegenerative disorder that has cerebral atrophy in the parietal, occipital, or occipitotemporal cortices and is characterized by visuospatial and visuoperceptual impairments. The most cases are pathologically compatible with Alzheimer's disease (AD). We describe a case of PCA in which a combination of imaging methods, in conjunction with symptoms and neurological and neuropsychological examinations, led to its being diagnosed and to AD being identified as its probable cause. Treatment with donepezil for 6 months mildly improved alexia symptoms, but other symptoms remained unchanged. A 59-year-old Japanese woman with progressive alexia, visual deficit, and mild memory loss was referred to our neurologic clinic for the evaluation of right homonymous hemianopsia. Our neurological examination showed alexia, constructional apraxia, mild disorientation, short-term memory loss, and right homonymous hemianopsia. These findings resulted in a score of 23 (of 30) points on the Mini-Mental State Examination. Occipital atrophy was identified, with magnetic resonance imaging (MRI) showing left-side dominance. The MRI data were quantified with voxel-based morphometry, and PCA was diagnosed on the basis of these findings. Single photon emission computed tomography with (123)I-N-isopropyl-p-iodoamphetamine showed hypoperfusion in the corresponding voxel-based morphometry occipital lobes. Additionally, the finding of hypoperfusion in the posterior associate cortex, posterior cingulate gyrus, and precuneus was consistent with AD. Therefore, the PCA was considered to be a result of AD. We considered Lewy body dementia as a differential diagnosis because of the presence of hypoperfusion in the occipital lobes. However, the patient did not meet the criteria for Lewy body dementia during the course of the disease. We therefore consider including PCA in the differential diagnoses to be important for patients with visual deficit, cognitive

  14. 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

  15. 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

  16. Memory binding and white matter integrity in familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

    2015-05-01

    Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to

  17. 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...

  18. Can statins prevent or help treat Alzheimer's disease?

    OpenAIRE

    McGuinness, Bernadette; Passmore, Peter

    2010-01-01

    Evidence accumulating from biological and epidemiological studies suggests that high levels of serum cholesterol may promote the pathological processes that lead to Alzheimer's disease (AD). Lowering cholesterol in experimental animal models slows the expression of Alzheimer's pathology. These findings raise the possibility that treating humans with cholesterol lowering medications might reduce the risk of developing AD or help treat it. The statins (lovastatin, pravastatin, simvastatin, and ...

  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. 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

  1. 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," ...

  2. 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 ...

  3. 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

  4. 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

  5. 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.

  6. 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.

  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. 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.

  9. 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 and...... hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited...

  10. Investigation of PSEN1, 2 Hot Spots in Iranian Early-Onset Alzheimer's Disease Patients

    OpenAIRE

    Leila Akbari; Maryam Noroozian; Parisa Azadfar; Samira Shaibaninia; Farhad Assarzadegan; Massoud Houshmand

    2015-01-01

    Background: Alzheimer's disease is a progressive, neurodegenerative disease with both genetic and non genetic causes. Familial Alzheimer's disease can be caused by mutations in the amyloid precursor protein, presenilin 1 and presenilin 2. Early-onset familial Alzheimer's disease (autosomal dominantly inherited) accounts for a small fraction (2-3%) of Alzheimer's disease cases. The aim of this study was investigation of exons 5, 7 in PSEN1 and exons 5, 6 in PSEN2 genes in Iranian patients with...

  11. 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

  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. Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

    Science.gov (United States)

    Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

    2014-03-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

  15. 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

  16. 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...

  17. 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...

  18. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010

    Science.gov (United States)

    2010-11-04

    ... disease represents a serious and growing threat to the health of our Nation, impacting millions of... States of America the two hundred and thirty-fifth. (Presidential Sig.) [FR Doc. 2010-28062 Filed 11-3-10... Documents#0;#0; ] Proclamation 8591 of October 29, 2010 National Alzheimer's Disease Awareness Month,...

  19. 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

  20. Pituitary gland levels of mercury, selenium, iron, and zinc in an Alzheimer`s disease study

    Energy Technology Data Exchange (ETDEWEB)

    Cornett, C.R.; Markesbery, W.R.; Wekstein, D.R.; Ehmann, W.D. [Univ. of Kentucky, Lexington, KY (United States)

    1996-12-31

    Mercury, iron, selenium, and zinc imbalances have been observed in comparisons between Alzheimer`s disease (AD) and control subject brains. Analyses of the pituitary gland have demonstrated that this organ retains relatively high concentrations of trace elements, including mercury, iron, and zinc. Our previous work has shown that the pituitary glands of AD and control subjects are typically higher in these trace elements than brain samples from the same subject. Instrumental neutron activation analysis (INAA) was used to compare the pituitary trace element levels of AD and control subjects. This study also describes the intrasubject relationships of brain trace element levels to those in the pituitary gland of AD and control subjects.

  1. 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.

  2. 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

  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...... 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. Brain ischemia with Alzheimer phenotype dysregulates Alzheimer's disease-related proteins.

    Science.gov (United States)

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Januszewski, Sławomir; Kocki, Janusz; Czuczwar, Stanisław J

    2016-06-01

    There are evidences for the influence of Alzheimer's proteins on postischemic brain injury. We present here an overview of the published evidence underpinning the relationships between β-amyloid peptide, hyperphosphorylated tau protein, presenilins, apolipoproteins, secretases and neuronal survival/death decisions after ischemia and development of postischemic dementia. The interactions of above molecules and their influence and contribution to final ischemic brain degeneration resulting in dementia of Alzheimer phenotype are reviewed. Generation and deposition of β-amyloid peptide and tau protein pathology are essential factors involved in Alzheimer's disease development as well as in postischemic brain dementia. Postischemic injuries demonstrate that ischemia may stimulate pathological amyloid precursor protein processing by upregulation of β- and γ-secretases and therefore are capable of establishing a vicious cycle. Functional postischemic brain recovery is always delayed and incomplete by an injury-related increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and β-amyloid peptide. Finally, we present here the concept that Alzheimer's proteins can contribute to and/or precipitate postischemic brain neurodegeneration including dementia with Alzheimer's phenotype. PMID:26940197

  8. Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease

    OpenAIRE

    Masse, I; Bordet, R; Deplanque, D; Al, K; Richard, F.; Libersa, C; Pasquier, F

    2005-01-01

    Background: Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer's disease susceptibility. Lipid lowering agents (LLAs) may have implications for the prevention of Alzheimer's disease.

  9. New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

    Science.gov (United States)

    ... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going ...

  10. 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

  11. Near infrared Raman spectroscopy for Alzheimer's disease detection

    Science.gov (United States)

    Sudworth, Caroline D.; Archer, John K. J.; Mann, David

    2005-08-01

    In recent years, the use of Raman spectroscopy for the detection and diagnosis of disease has steadily grown within the research field. However, this research has primarily been restricted to oncology. This research expands the use of Raman spectroscopy as a potential tool for the diagnosis of Alzheimer's disease, which is currently the most prevalent, and fastest growing type of dementia in the Western world. Using a commercial Raman spectrometer (Renishaw PLC ®, UK) flash frozen post-mortem ex vivo brain tissue sections were illuminated using a high power (20mW) 830 nm near infrared diode laser, and subsequently spectra were gained in the region of 2000-200 cm-1 from a 10 second accumulation time. Ethical approval was gained for the examination of 18 individual donors exhibiting varying states of Alzheimer's disease, Huntingdon's disease and their corresponding age-matched healthy controls. Following on from previous preliminary studies, the Raman spectra were found to be highly reproducible, and when examined further, the spectra showed differences relating to the content and structure of the proteins in the individual brain samples, in particular, the beta-amyloid protein structure found in Alzheimer's disease patients. Principle components analysis further determined these protein structural changes, with Alzheimer's disease and Huntingdon's disease samples being defined from the healthy controls, and from each other.

  12. 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

  13. Statistical physics approaches to Alzheimer's disease

    Science.gov (United States)

    Peng, Shouyong

    Alzheimer's disease (AD) is the most common cause of late life dementia. In the brain of an AD patient, neurons are lost and spatial neuronal organizations (microcolumns) are disrupted. An adequate quantitative analysis of microcolumns requires that we automate the neuron recognition stage in the analysis of microscopic images of human brain tissue. We propose a recognition method based on statistical physics. Specifically, Monte Carlo simulations of an inhomogeneous Potts model are applied for image segmentation. Unlike most traditional methods, this method improves the recognition of overlapped neurons, and thus improves the overall recognition percentage. Although the exact causes of AD are unknown, as experimental advances have revealed the molecular origin of AD, they have continued to support the amyloid cascade hypothesis, which states that early stages of aggregation of amyloid beta (Abeta) peptides lead to neurodegeneration and death. X-ray diffraction studies reveal the common cross-beta structural features of the final stable aggregates-amyloid fibrils. Solid-state NMR studies also reveal structural features for some well-ordered fibrils. But currently there is no feasible experimental technique that can reveal the exact structure or the precise dynamics of assembly and thus help us understand the aggregation mechanism. Computer simulation offers a way to understand the aggregation mechanism on the molecular level. Because traditional all-atom continuous molecular dynamics simulations are not fast enough to investigate the whole aggregation process, we apply coarse-grained models and discrete molecular dynamics methods to increase the simulation speed. First we use a coarse-grained two-bead (two beads per amino acid) model. Simulations show that peptides can aggregate into multilayer beta-sheet structures, which agree with X-ray diffraction experiments. To better represent the secondary structure transition happening during aggregation, we refine the

  14. 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.

  15. How close is the stem cell cure to the Alzheimer's disease

    OpenAIRE

    Tang, Jun

    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.

  16. 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

  17. 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

  18. Basal forebrain atrophy correlates with amyloid β burden in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Georg M Kerbler

    2015-01-01

    Full Text Available The brains of patients suffering from Alzheimer's disease (AD have three classical pathological hallmarks: amyloid-beta (Aβ plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Aβ burden and basal forebrain degeneration has not been extensively studied. To investigate this association, basal forebrain volumes were determined from magnetic resonance images of controls, subjects with amnestic mild cognitive impairment (aMCI and AD patients enrolled in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI and Australian Imaging, Biomarkers and Lifestyle (AIBL studies. In the AIBL cohort, these volumes were correlated within groups to neocortical gray matter retention of Pittsburgh compound B (PiB from positron emission tomography images as a measure of Aβ load. The basal forebrain volumes of AD and aMCI subjects were significantly reduced compared to those of control subjects. Anterior basal forebrain volume was significantly correlated to neocortical PiB retention in AD subjects and aMCI subjects with high Aβ burden, whereas posterior basal forebrain volume was significantly correlated to neocortical PiB retention in control subjects with high Aβ burden. Therefore this study provides new evidence for a correlation between neocortical Aβ accumulation and basal forebrain degeneration. In addition, cluster analysis showed that subjects with a whole basal forebrain volume below a determined cut-off value had a 7 times higher risk of having a worse diagnosis within ~18 months.

  19. 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

  20. 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

  1. 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.

  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. 3 CFR 8446 - Proclamation 8446 of October 30, 2009. National Alzheimer's Disease Awareness Month, 2009

    Science.gov (United States)

    2010-01-01

    ... debilitating physical and mental impairments. As we seek hope for families struggling with Alzheimer's disease... Alzheimer's Disease Awareness Month, 2009 8446 Proclamation 8446 Presidential Documents Proclamations Proclamation 8446 of October 30, 2009 Proc. 8446 National Alzheimer's Disease Awareness Month, 2009By...

  4. 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

  5. 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)....

  6. 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)

  7. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

    Energy Technology Data Exchange (ETDEWEB)

    Campion, D. [INSERM, Paris (France); Martinez, M.; Babron, M.C. [and others

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrant by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.

  8. 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).......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)....

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

    OpenAIRE

    Robbins, J H; Otsuka, F; Tarone, R E; Polinsky, R J; Brumback, R A; Nee, L.E.

    1985-01-01

    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 no...

  10. 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…

  11. 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…

  12. 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

  13. Alzheimer's Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms

    Science.gov (United States)

    Hollands, Carolyn; Bartolotti, Nancy; Lazarov, Orly

    2016-01-01

    New neurons incorporate into the granular cell layer of the dentate gyrus throughout life. Neurogenesis is modulated by behavior and plays a major role in hippocampal plasticity. Along with older mature neurons, new neurons structure the dentate gyrus, and determine its function. Recent data suggest that the level of hippocampal neurogenesis is substantial in the human brain, suggesting that neurogenesis may have important implications for human cognition. In support of that, impaired neurogenesis compromises hippocampal function and plays a role in cognitive deficits in Alzheimer's disease mouse models. We review current work suggesting that neuronal differentiation is defective in Alzheimer's disease, leading to dysfunction of the dentate gyrus. Additionally, alterations in critical signals regulating neurogenesis, such as presenilin-1, Notch 1, soluble amyloid precursor protein, CREB, and β-catenin underlie dysfunctional neurogenesis in Alzheimer's disease. Lastly, we discuss the detectability of neurogenesis in the live mouse and human brain, as well as the therapeutic implications of enhancing neurogenesis for the treatment of cognitive deficits and Alzheimer's disease. PMID:27199641

  14. The impact of Alzheimer's Disease on the Chinese economy

    DEFF Research Database (Denmark)

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

    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...

  15. 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

  16. 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

  17. 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…

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Surface plasmon resonance biosensors for detection of Alzheimer disease biomarkers

    Czech Academy of Sciences Publication Activity Database

    Hegnerová, Kateřina; Bocková, Markéta; Vaisocherová, Hana; Krištofíková, Z.; Říčný, J.; Řípová, D.; Homola, Jiří

    2009-01-01

    Roč. 139, č. 1 (2009), s. 69-73. ISSN 0925-4005 R&D Projects: GA MZd NR9322; GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z20670512 Keywords : Alzheimer disease * SPR sensor * 17beta-HSD10 Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.083, year: 2009

  4. Inhibitors of glutaminyl cyclases against Alzheimer´s disease

    Czech Academy of Sciences Publication Activity Database

    Kolenko, Petr; Koch, B.; Schilling, S.; Rahfeld, J.-U.; Demuth, H.-U.; Stubbs, M. T.

    2013-01-01

    Roč. 20, č. 1 (2013), s. 16. ISSN 1211-5894. [Discussions in Structural Molecular Biology /11./. 14.03.2013-16.03.2013, Nové Hrady] R&D Projects: GA MŠk EE2.3.30.0029 Institutional support: RVO:61389013 Keywords : glutaminyl cyclases * Alzheimer ´s disease Subject RIV: CE - Biochemistry

  5. 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...

  6. [Treatment of patients with Alzheimer's disease: a breakthrough or not?].

    Science.gov (United States)

    van Marum, Rob J

    2015-01-01

    The results of an open-label extension study of the Expedition I and II studies with solanezumab in patients with Alzheimer's disease, neither of which had shown an effect on cognition and functional ability, were recently presented at the Alzheimer's Association International Conference in Toronto. Placebo and intervention patients with mild Alzheimer's disease from both studies were offered the option of continuing with solanezumab for 2 additional years. The data from this group were re-analysed using a new analysis technique, the so-called 'delayed start analysis'. On the basis of the re-analysis it was concluded that solanezumab does show disease-modifying activity and should be considered a promising candidate for treatment of Alzheimer's disease in the near future. This conclusion, however, is poorly supported by the data presented in the study. A more definite positioning of solanezumab will not be possible until data from the ongoing Expedition III study becomes available in 2017 at the earliest. PMID:26271177

  7. 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

  8. 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.

  9. 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…

  10. 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…

  11. Taking Control of Alzheimer's Disease: A Training Evaluation

    Science.gov (United States)

    Silverstein, Nina M.; Sherman, Robin

    2010-01-01

    The purpose of the current study was to evaluate a training program for persons with early-stage Alzheimer's disease and their care partners. Care partners were mailed two surveys, one for themselves and one for the person with dementia. Domains covered in the training included an overview of cognitive disorders, treatment of symptoms including…

  12. 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...

  13. Assessing Impact on Family Caregivers to Alzheimer's Disease Patients.

    Science.gov (United States)

    Talkington-Boyer, Shannon; Snyder, Douglas K.

    1994-01-01

    Examined impact of caregiving among 110 caregivers to aging family member with Alzheimer's disease. Family caregivers' appraisals along dimensions of subjective burden, negative impact, caregiving satisfaction, and caregiver mastery were correlated with extent of memory and behavior problems of patient and caregivers' coping style, locus of…

  14. Metabolic profiling distinguishes three subtypes of Alzheimer's disease

    OpenAIRE

    Bredesen, Dale E.

    2015-01-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report tha...

  15. 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

  16. 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, ...

  17. 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 . ...

  18. [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

  19. 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.

  20. Is Alzheimer disease related to age-related macular degeneration?

    OpenAIRE

    DEMİRCİ, Seden; GÜNEŞ, ALİME; Demi̇rci̇, Kadi̇r; DEMİRCİ, SERPİL; Tök, Levent; Tök, Özlem

    2015-01-01

    Background/aim: To compare the cognitive functions and define the frequency of Alzheimer disease (AD) between participants with and without age-related macular degeneration (AMD). Materials and methods: Fifty-nine patients with late-stage AMD (74.3 ± 7.3 years) and 49 age-, sex-, and education-matched control subjects were compared for the presence of AD according to the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disea...

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Cerebrospinal Fluid Alzheimer Markers in Depressed Elderly Subjects with and without Alzheimer's Disease

    OpenAIRE

    Kramberger, Milica Gregoric; Jelic, Vesna; Kåreholt, Ingemar; Enache, Daniela; Eriksdotter Jönhagen, Maria; Winblad, Bengt; Aarsland, Dag

    2012-01-01

    Background The aim of this study was to explore the relationship between cerebrospinal fluid Alzheimer's disease (AD) markers and depression in elderly people. Method We included subjects with AD as well as persons with subjective cognitive impairment and normal cognition. Depression was assessed with the Cornell Scale for Depression in Dementia, and a cut-off score of >6 was used to define depression. Cerebrospinal fluid was analyzed using commercially available assays for β-amyloid 1–42, to...

  6. 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. ...

  7. 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.

  8. 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)

  9. 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...

  10. 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

  11. Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease?

    OpenAIRE

    McLachlan, D R; Kruck, T P; Lukiw, W J; Krishnan, S.S.

    1991-01-01

    Although the cause of Alzheimer's disease (AD) remains unknown there is mounting evidence that implicates aluminum as a toxic environmental factor of considerable importance. Four independent lines of evidence--laboratory studies of the effects of intracerebral aluminum on the cognitive and memory performance of animals, biochemical studies, epidemiologic studies and the slowing of the progress of the disease with the use of an agent that removes aluminum from the body--now support the concep...

  12. Phosphoproteomic Profiling of Selenate-Treated Alzheimer's Disease Model Cells

    OpenAIRE

    Ping CHEN; Wang, Lixiang; Wang, Yong; Li, Shuiming; Shen, Liming; Liu, Qiong; Ni, Jiazuan

    2014-01-01

    The reversible phosphorylation of proteins regulates most biological processes, while abnormal phosphorylation is a cause or consequence of many diseases including Alzheimer's disease (AD). One of the hallmarks of AD is the formation of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau proteins. Sodium selenate has been recently found to reduce tau hyperphosphorylation and NFTs formation, and to improve spatial learning and motor performance in AD mice. In the curre...

  13. 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

  14. 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.

  15. 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 ...

  16. 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

  17. Lost in Translation: Epidemiology, Risk, and Alzheimer's Disease

    OpenAIRE

    Ganguli, Mary; Kukull, Walter A.

    2010-01-01

    There is increasing emphasis on interdisciplinary “translation” in biomedical research.1 A major push towards prevention of Alzheimer's Disease is spawning translational research 2 that should span basic, clinical, and population investigations. Epidemiological studies, which address our understanding of risk and protective factors for disease at the population level, are contributing less than they could to translational research. In part, this is because the key concept of risk is being “lo...

  18. Modeling an Anti-Amyloid Combination Therapy for Alzheimer's Disease

    OpenAIRE

    Chow, Vivian W.; Savonenko, Alena V; Melnikova, Tatiana; Kim, Hyunsu; Price, Donald L.; Li, Tong; Wong, Philip C.

    2010-01-01

    As only symptomatic treatments are now available for Alzheimer's disease (AD), safe and effective mechanism-based therapies remain a great unmet need for patients with this neurodegenerative disease. Although γ-secretase and BACE1 [β-site β-amyloid (Aβ) precursor protein (APP) cleaving enzyme 1] are well-recognized therapeutic targets for AD, untoward side effects associated with strong inhibition or reductions in amounts of these aspartyl proteases have raised concerns regarding their therap...

  19. Animal models for Alzheimer's disease and frontotemporal dementia: a perspective

    OpenAIRE

    Jürgen Götz; Naeman N Götz

    2009-01-01

    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 ...

  20. 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

  1. Targeting Gonadotropins: An Alternative Option for Alzheimer Disease Treatment

    OpenAIRE

    Gemma Casadesus; Emma Ramiro Puig; Webber, Kate M.; Atwood, Craig S.; Margarida Castell Escuer; Bowen, Richard L.; George Perry; Smith, Mark A

    2006-01-01

    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 dur...

  2. Evaluation of medication treatment for Alzheimer's disease on clinical evidence

    Directory of Open Access Journals (Sweden)

    Meng-qiu LI

    2014-03-01

    Full Text Available Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT, controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7, and 5 were low quality with score 3. It was summarized as follows: 1 Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine and an N-methyl-D-aspartate (NMDA receptor noncompetitive antagonist (memantine, are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2 Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009

  3. 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.

  4. 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.

  5. 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 Alzheimer’s Disease Assessment Scale cognitive subscale scores (β [SE], 0.405 [0.190]; P = .03). Regarding gene expression, HLA-DRA and IPMK transcript expression was significantly altered in AD brains compared with control brains (HLA-DRA: β [SE], 0.155 [0.024]; P = 1.97 × 10−10; IPMK: β [SE], −0

  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. PMID:24339113

  7. 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

  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. 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.

  10. 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.

  11. 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

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

    DEFF Research Database (Denmark)

    Sparre-Sørensen, Maja; Kristensen, Gustav David Westergaard

    2015-01-01

    significant increase in the number of deaths related to malnutrition was found among the elderly in Denmark. Many more may have been suffering from malnutrition, but not to such a degree that it led to their deaths. OBJECTIVE: The aim of this study is to examine whether or not the effect of the malnutrition...... 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, and......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...

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. Apolipoprotein E in the genetics and epidemiology of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, J. [Univ. of South Florida, Tampa, FL (United States)

    1995-10-09

    The role of apolipoprotein E (ApoE) alleles and isoforms in the etiology and pathogenesis of Alzheimer`s disease is discussed. The possibility that ApoE itself is not involved in the disease pathogenesis but is merely in genetic disequilibrium with the real locus is discussed and dismissed. The data showing that the {epsilon}4 allele is associated with an increased risk of developing the disease and with an earlier onset age are reviewed. The data showing that, at least in some circumstances, the {epsilon}2 allele is associated with a decrease in the risk of developing the disease, and with a later onset age are also reviewed. Data from the genetic analysis of other disorders are reviewed and presented, and it is suggested that the genetic data support the notion that the role of ApoE in the etiology of the disease directly relates to {beta}-amyloid deposition and plaque formation. This suggestion is in concordance with the most likely mechanism for the role of P-amyloid precursor protein gene mutations as other risk factors for the disease. 68 refs.

  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

    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

  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. Construction of a yeast artificial chromosome contig encompassing the chromosome 14 Alzheimer`s disease locus

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, V.; Bonnycastle, L.; Poorkai, P. [Univ. of Washington, Seattle, WA (United States)] [and others

    1994-09-01

    We have constructed a yeast artificial chromosome (YAC) contig of chromosome 14q24.3 which encompasses the chromosome 14 Alzheimer`s disease locus (AD3). Determined by linkage analysis of early-onset Alzheimer`s disease kindreds, this interval is bounded by the genetic markers D14S61-D14S63 and spans approximately 15 centimorgans. The contig consists of 29 markers and 74 YACs of which 57 are defined by one or more sequence tagged sites (STSs). The STS markers comprise 5 genes, 16 short tandem repeat polymorphisms and 8 cDNA clones. An additional number of genes, expressed sequence tags and cDNA fragments have been identified and localized to the contig by hybridization and sequence analysis of anonymous clones isolated by cDNA direct selection techniques. A minimal contig of about 15 YACs averaging 0.5-1.5 megabase in length will span this interval and is, at first approximation, in rough agreement with the genetic map. For two regions of the contig, our coverage has relied on L1/THE fingerprint and Alu-PCR hybridization data of YACs provided by CEPH/Genethon. We are currently developing sequence tagged sites from these to confirm the overlaps revealed by the fingerprint data. Among the genes which map to the contig are transforming growth factor beta 3, c-fos, and heat shock protein 2A (HSPA2). C-fos is not a candidate gene for AD3 based on the sequence analysis of affected and unaffected individuals. HSPA2 maps to the proximal edge of the contig and Calmodulin 1, a candidate gene from 4q24.3, maps outside of the region. The YAC contig is a framework physical map from which cosmid or P1 clone contigs can be constructed. As more genes and cDNAs are mapped, a highly resolved transcription map will emerge, a necessary step towards positionally cloning the AD3 gene.

  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. 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

  6. Withanolides: Biologically Active Constituents in the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Khan, Shahid A; Khan, Sher B; Shah, Zarbad; Asiri, Abdullah M

    2016-01-01

    The use of natural products in drug discovery and development have an important history. Several therapeutic agents have been investigated during the biological screenings of natural compounds. It is well documented that plants are possibly the core of novel substances that led to the discovery of new, novel, and effective therapeutic agents. Therefore, in the last few decades, scientists were thoroughly attempting for the search of benevolent drugs to protect mankind from various diseases and discomforts. The diverse chemical structures of natural products are the key element of their success in modern drug discovery. Cholinesterase enzyme inhibitors (ChEI) are chemicals which inhibit the splitting of cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase). Acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) are two types of cholinesterase enzymes that have been identified in vertebrates that are responsible for Alzheimer's disease and related dementia. Withanolides are affective plant secondary metabolites which inhibit acetylcholinesterase and butyrylcholinesterase enzyme and thus possibly will be the future drug for Alzheimer's disease. By viewing the importance of natural products in drug discovery and development, we present here, the importance of withanolides in the treatment of Alzheimer's disease. In this article, we also describe the classification and structural characterization of withanolides. This review comprises of 114 compounds. PMID:26527154

  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. 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

  10. 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

  11. 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.

  12. 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 was...... taken as the standard. It was also investigated whether the two episodic memory tests correlated with measures of semantic memory. The tests were administered to 35 patients with very mild AD (Mini Mental State Examination score > 22) and 28 control subjects. Both tests had high sensitivity (>88%) with...

  13. Alzheimer's Disease: Mechanism and Approach to Cell Therapy.

    Science.gov (United States)

    Amemori, Takashi; Jendelova, Pavla; Ruzicka, Jiri; Urdzikova, Lucia Machova; Sykova, Eva

    2015-01-01

    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. PMID:26556341

  14. Alzheimer's Project

    Medline Plus

    Full Text Available ... thinks about Alzheimer's disease. Tell your family and friends. Post info on your Web site . Become an Alzheimer's champion. Help support vital research and services. "THE ALZHEIMER'S PROJECT" is a presentation ...

  15. Statins and therapy of Alzheimer's disease: questions of efficacy versus trial design

    OpenAIRE

    Wolozin, Benjamin

    2012-01-01

    Recent trials of statins produced no benefit for subjects with Alzheimer's disease. These negative studies add to a growing list of negative clinical trials. These data point to a need for reevaluating the pathophysiology of late-onset Alzheimer's disease. Late-onset Alzheimer's disease might result from the cumulative effects of at least four different factors: β-amyloid accumulation, cardiovascular disease, aging and the associated loss of synaptic plasticity, and inflammation. Successful t...

  16. Computational model for astroglial cell function in Alzheimer's disease

    OpenAIRE

    Eeva Mäkiraatikka; Amit K Nahata; Jalonen, Tuula O.

    2008-01-01

    Neuritic plaques, consisting mostly of aggregated amyloid-β peptide, are some of the pathological findings in brains of Alzheimer's disease patients. The aggregated amyloid-β disturbs the cellular homeostasis, which can be monitored by e.g. measuring changes in the intracellular Ca2+ concentrations [Ca2+]. As an intracellular second messenger, Ca2+ functions as a mediator in transporting extracellular signals into the cell. Normally, the Ca2+ concentration in the cytosol is kept...

  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. Specificity of Inhibitory Deficits in Normal Aging and Alzheimer's Disease

    OpenAIRE

    Collette, Fabienne; Schmidt, Christina; Scherrer, Christine; Adam, Stéphane; Salmon, Eric

    2009-01-01

    Deficits of suppression abilities are frequently observed in normal aging and Alzheimer's disease. However, few studies have explored these deficits in the two populations simultaneously using a large battery of tasks. The aim of the present study was to explore if the pattern of performance presented by elderly subjects and AD patients is in agreement with theoretical frameworks [Wilson, S.P., Harnishfeger, K.K., 1998. The development of efficient inhibition: Evidence from directed forgettin...

  19. PET molecular probes for early detection of Alzheimer's disease

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. The characteristic pathological lesions are deposits of β-amyloid plaques and neurofibrillary tangles after postmortem examination, and degeneration of cholinergic neurons of the basal forebrain. The positron emission tomography (PET) molecular probes targeting at β-amyloid plaques or acetylchergic is one of the most reliable tools for AD early detection. (authors)

  20. Alzheimer's Disease Classification using K-OPLS and MRI

    OpenAIRE

    Falahati Asrami, Farshad

    2012-01-01

    In this thesis, we have used the kernel based orthogonal projection to latent structures (K-OPLS) method to discriminate between Alzheimer's Disease patients (AD) and healthy control subjects (CTL), and to predict conversion from mild cognitive impairment (MCI) to AD. In this regard three cohorts were used to create two different datasets; a small dataset including 63 subjects based on the Alzheimer’s Research Trust (ART) cohort and a large dataset including 1074 subjects combining the AddNeu...

  1. Involvement of mirror neuron system in prodromal Alzheimer's disease

    OpenAIRE

    Moretti, D. V.

    2016-01-01

    Background Mirror neurons have been localized in several locations, including the inferior parietal lobule (IPL). Increase of EEG alpha3/alpha2 frequency power ratio has been detected in mild cognitive impairment (MCI) subjects who will convert in Alzheimer's disease (AD). We investigated the association of alpha3/alpha2 frequency power ratio with cortical thickness in IPL in MCI subjects. Methods 74 adult subjects with MCI underwent EEG recording and high resolution MRI. Alpha3/alpha2 freque...

  2. Inflammation as a therapeutic target for Alzheimer s disease

    OpenAIRE

    Hjorth, Erik

    2010-01-01

    Alzheimer s disease (AD) is a progressive neurodegenerative disorder which is characterised by impairment of memory and learning. The impairment is caused by neuronal death which originates in the parts of the brain that execute memory functions: the entorhinal cortex and hippocampus. The neuronal death is believed to be caused by the amyloid- (A) peptide which is prone to oligomerisation and aggregation into insoluble amyloid plaques (AP). The levels of soluble A and the nu...

  3. 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.

  4. 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

  5. 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...

  6. Caregiver Burden and Psychoeducational Interventions in Alzheimer's Disease: A Review

    OpenAIRE

    Beinart, N.; Weinman, J; Wade, D; Brady, R

    2012-01-01

    Background Caring for a patient with Alzheimer's disease (AD) is associated with poor quality of life and deteriorating health for the caregiver. Methods This comprehensive review was performed to investigate the current literature on caregiver burden, factors affecting caregiver burden and the effectiveness of different types of intervention. Results Successful psychoeducational interventions for caregivers have included provision of information about AD, care planning, advice about patient ...

  7. 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...

  8. Why nutraceuticals do not prevent or treat Alzheimer's disease

    OpenAIRE

    Naughton Declan P; Fisher Anna EO

    2005-01-01

    Abstract A great deal of research has pointed to deleterious roles of metal ions in the development of Alzheimer's disease. These include: i) the precipitation and aggregation of amyloid β (Aβ) peptides to form senile plaques and neurofibrillary tangles, and/or ii) the augmentation of oxidative stress by metal ion mediated production and activation of hydrogen peroxide. The growing trend in nutraceutical intake is in part a result of the belief that they postpone the development of dementias ...

  9. Stress, exercise, and Alzheimer's disease: A neurovascular pathway

    OpenAIRE

    Nation, Daniel A.; Hong, Suzi; Jak, Amy J.; Delano-Wood, Lisa; Mills, Paul J.; Bondi, Mark W; Joel E Dimsdale

    2011-01-01

    Genetic factors are known to play a role in Alzheimer's disease (AD) vulnerability, yet less than 1% of incident AD cases are directly linked to genetic causes, suggesting that environmental variables likely play a role in the majority of cases. Several recent human and animal studies have examined the effects of behavioral factors, specifically psychological stress and exercise, on AD vulnerability. Numerous animal studies have found that, while stress exacerbates neuropathological changes a...

  10. Behavioural genetics of Alzheimer's disease: a comprehensive review

    OpenAIRE

    Flirski, Marcin; Sobow, Tomasz; Kloszewska, Iwona

    2011-01-01

    Behavioural and psychological symptoms of dementia (BPSD) are present in the course of the illness in up to 90% of patients with Alzheimer's disease (AD). They are the main source of caregiver burden and one of the major factors contributing to early institutionalization. The involvement of a genetic component in BPSD aetiology seems beyond controversy, though the exact significance of particular polymorphisms is uncertain in the majority of cases. Multiple genes have been assessed for their ...

  11. 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...

  12. 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...

  13. 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...

  14. A Review: Inflammatory Process in Alzheimer's Disease, Role of Cytokines

    OpenAIRE

    Jose Miguel Rubio-Perez; Juana Maria Morillas-Ruiz

    2012-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder to date. Neuropathological hallmarks are β -amyloid (A β ) plaques and neurofibrillary tangles, but the inflammatory process has a fundamental role in the pathogenesis of AD. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the complement system, as well as cytokines and chemokines. Cytokines play a key role in inflammatory and anti-inflammatory processes in AD. ...

  15. Targeting HDACs: A Promising Therapy for Alzheimer's Disease

    OpenAIRE

    Ke Xu; Xue-Ling Dai; Han-Chang Huang; Zhao-Feng Jiang

    2011-01-01

    Epigenetic modifications like DNA methylation and histone acetylation play an important role in a wide range of brain disorders. Histone deacetylases (HDACs) regulate the homeostasis of histone acetylation. Histone deacetylase inhibitors, which initially were used as anticancer drugs, are recently suggested to act as neuroprotectors by enhancing synaptic plasticity and learning and memory in a wide range of neurodegenerative and psychiatric disorders, such as Alzheimer's disease (AD) and Park...

  16. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy

    OpenAIRE

    Zotova, Elina; Nicoll, James A. R.; Kalaria, Raj; Holmes, Clive; Boche, Delphine

    2010-01-01

    Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this hypothesis, the inflammatory reaction is still considered to be a downstream effect of the accumulated proteins (amyloid beta (Abeta) and tau). This review aims to highlight the importance of the immune processes involved in AD pathogenesis based...

  17. Novel immunological approaches for the treatment of Alzheimer's disease

    OpenAIRE

    Priyanka Sabharwal; Thomas Wisniewski

    2014-01-01

    Alzheimer's disease (AD), the most prevalent form of dementia worldwide, can be deemed as the next global health epidemic. The biochemistry underlying deposition of amyloid beta (A β) and hyperphosphorylated tau aggregates in AD has been extensively studied. The oligomeric forms of Aβ that are derived from the normal soluble Aβ peptides are believed to be the most toxic. However, it is the fibrillar Aβ form that aggregates as amyloid plaques and cerebral amyloid angiopathy, which serve as pat...

  18. Recent preclinical evidence advancing cell therapy for Alzheimer's disease

    OpenAIRE

    Borlongan, Cesar V.

    2012-01-01

    Alzheimer's disease (AD) causes brain degeneration, primarily depleting cholinergic cells, and leading to cognitive and learning dysfunction. Logically, to augment the cholinergic cell loss, a viable treatment for AD has been via drugs boosting brain acetylcholine production. However, this is not a curative measure. To this end, nerve growth factor (NGF) has been examined as a possible preventative treatment against cholinergic neuronal death while enhancing memory capabilities; however, NGF ...

  19. Staging Anti-Inflammatory Therapy in Alzheimer's Disease

    OpenAIRE

    Lichtenstein, Mathieu P.; Carriba, Paulina; Masgrau, Roser; Pujol, Aurora; Galea, Elena

    2010-01-01

    The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics in light of: (i) the last report from the only primary prevention trial in AD, ADAPT, which, although incomplete, points to significant protection in long-ter...

  20. Leptin: A Novel Therapeutic Strategy for Alzheimer's Disease

    OpenAIRE

    Tezapsidis, Nikolaos; Johnston, Jane M.; Smith, Mark A; Ashford, J. Wesson; Casadesus, Gemma; Robakis, Nikolaos K.; Wolozin, Benjamin; Perry, George; Zhu, Xiongwei; Greco, Steven J.; Sarkar, Sraboni

    2009-01-01

    Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. One activity of leptin is the control of AMP-dependent kinase (AMPK). In addition to maintaining lipid levels, AMPK regulates glycogen synthase kinase-3, which modulates tau phosphorylation. Leptin has been shown to reduce the amount of extracellular amyloid-β, both in cell culture and animal models of AD, as well as reduce tau phosphorylation in neuron...

  1. 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

  2. PET studies in Alzheimer disease and other degenerative dementias

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yong; Na, Duk L. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-02-01

    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.

  3. 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

  4. 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

  5. [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

  6. A diagnostic approach in Alzheimer`s disease using three-dimensional stereotactic surface projections of Fluorine-18-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Minoshima, S.; Frey, K.A.; Koeppe, R.A. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1995-07-01

    To improve the diagnostic performance of PET as an aid in evaluating patients suspected of having Alzheimer`s disease, the authors developed a fully automated method which generates comprehensive image presentations and objective diagnostic indices. Fluorine-18-fluorodeoxyglucose PET image sets were collected from 37 patients with probable Alzheimer`s disease (including questionable and mild dementia), 22 normal subjects and 5 patients with cerebrovascular disease. Following stereotactic anatomic standardization, metabolic activity on an individual`s PET image set was extracted to a set of predefined surface pixels (three-dimensional stereotactic surface projection, 3D-SSP), which was used in the subsequent analysis. A normal database was created by averaging extracted datasets of the normal subjects. Patients` datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspections. Diagnostic indices were then generated based on averaged Z-scores for the association cortices. Patterns and severities of metabolic reduction in patients with probable Alzheimer`s disease were seen in the standard 3D-SSP views of extracted raw data and statistical Z-scores. When discriminating patients with probable Alzheimer`s disease from normal subjects, diagnostic indices of the parietal association cortex and unilaterally averaged parietal-temporal-frontal cortex showed sensitivities of 95% and 97%, respectively, with a specificity of 100%. Neither index yielded false-positive results for cerebrovascular disease. 3D-SSP enables quantitative data extraction and reliable localization of metabolic abnormalities by means of stereotactic coordinates. The proposed method is a promising approach for interpreting functional brain PET scans. 45 refs., 5 figs.

  7. 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)

  8. Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Shoffner, J.M.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)] [and others

    1996-01-22

    The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.

  9. New Genes Tied to Alzheimer's Disease

    Science.gov (United States)

    ... Disease The Mechanism of Muscle Loss in Cancer Epigenetic Clock Marks Age of Human Tissues and Cells ... General USA.gov – Government Made Easy NIH…Turning Discovery Into Health ® National Institutes of Health, 9000 Rockville ...

  10. 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...

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Benzodiazepine receptor and cerebral blood flow in early Alzheimer`s disease. SPECT study using {sup 123}I-Iomazenil and {sup 123}I-IMP

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Shin; Koshi, Yasuhiko; Komiyama, Tasuku; Sakayori, Osamu; Komaba, Yuichi; Ohyama, Masashi; Mishina, Masahiro; Tsuganesawa, Toshikazu; Terashi, Akiro [Nippon Medical School, Tokyo (Japan). First Hospital

    1996-01-01

    This study was designed to investigate benzodiazepine receptors (BZR) and cerebral blood flow (CBF) in patients with early Alzheimer`s disease. Imaging of BZR and measurement of CBF were performed by SPECT using {sup 123}I-Iomazenil (IMZ) and {sup 123}I-IMP respectively, in seven patients with early Alzheimer`s disease and five patients with unilateral left cerebral infarction as controls. The values for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with cerebral infarction were adopted as control values. In patients with Alzheimer`s disease, the CBF (ratio to cerebellum) decreased significantly in the frontal cortex and the parietal cortex compared with the control values. There was no significant difference in late IMZ SPECT counts (ratio to cerebellum) and washout (the ratio of late-to-early IMZ SPECT counts) between patients with Alzheimer`s disease and the controls. However, the late IMZ SPECT counts and washout decreased in one patient with moderate dementia. There was a significant correlation between the severity of dementia and the late IMZ SPECT counts in the temporal cortex and the parietal cortex. These results suggest that benzodiazepine binding sites are relatively well preserved in patients with early Alzheimer`s disease, and reduction of the CBF is caused by neuronal dysfunction rather than by neuronal loss. IMZ SPECT study is useful and necessary for clarifying the pathophysiological state in Alzheimer`s disease. (author).

  19. 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.)

  20. Radiosensitivity of lymphocytes from patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    The response after γ-irradiation of lymphocytes from 8 patients with Alzheimer's disease (AD), 3 patients with Huntington's disease and 13 normal subjects to stimulation by photohaemagglutinin (PHA) was assayed by incorporation of (3 H) thymidine. The response of non-irradiated cells was found to be significantly lower in AD cells than in age-matched normals but not significantly lower in old normals than in young normals. However, the response of irradiated cells to PHA, expressed as a percentage of that in non-irradiated cells, was found to be similar in AD patients, young and old normals and in HD patients. (author). 17 refs.; 8 figs