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Sample records for alzheimers disease neuroimaging

  1. Neuroimaging of Alzheimer's disease

    International Nuclear Information System (INIS)

    Matsuda, Hiroshi

    2005-01-01

    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. Neuroimaging Measures as Endophenotypes in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Meredith N. Braskie

    2011-01-01

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

  3. Molecular neuroimaging of Alzheimer's disease

    NARCIS (Netherlands)

    Nabuurs, Rob Johannes Antonius

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Sidong eLiu

    2016-02-01

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

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

    International Nuclear Information System (INIS)

    Arai, Hiroyuki; Furukawa, Katsutoshi; Okamura, Nobuyuki; Kudo, Yukitsuka

    2010-01-01

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

  8. Neuroimaging and the search for a cure for Alzheimer disease.

    Science.gov (United States)

    Petrella, Jeffrey R

    2013-12-01

    As radiologists, our role in the workup of the dementia patient has long been limited by the sensitivity of our imaging tools and lack of effective treatment options. Over the past 30 years, we have made tremendous strides in understanding the genetic, molecular, and cellular basis of Alzheimer disease (AD). We now know that the pathologic features of AD are present 1 to 2 decades prior to development of symptoms, though currently approved symptomatic therapies are administered much later in the disease course. The search for true disease-modifying therapy continues and many clinical trials are underway. Current outcome measures, based on cognitive tests, are relatively insensitive to pathologic disease progression, requiring long, expensive trials with large numbers of participants. Biomarkers, including neuroimaging, have great potential to increase the power of trials by matching imaging methodology with therapeutic mechanism. One of the most important advances over the past decade has been the development of in vivo imaging probes targeted to amyloid beta protein, and one agent is already available for clinical use. Additional advances include automated volumetric imaging methods to quantitate cerebral volume loss. Use of such techniques in small, early phase trials are expected to significantly increase the number and quality of candidate drugs for testing in larger trials. In addition to a critical role in trials, structural, molecular, and functional imaging techniques can give us a window on the etiology of AD and other neurodegenerative diseases. This combination of developments has potential to bring diagnostic radiology to the forefront in AD research, therapeutic trials, and patient care. ©RSNA, 2013.

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

    DEFF Research Database (Denmark)

    Buerger, Katharina; Frisoni, Giovanni; Uspenskaya, Olga

    2009-01-01

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

  10. Structural Neuroimaging of the Medial Temporal Lobe in Alzheimer's Disease Clinical Trials.

    Science.gov (United States)

    Menéndez-González, Manuel; de Celis Alonso, Benito; Salas-Pacheco, José; Arias-Carrión, Oscar

    2015-01-01

    Atrophy in the medial temporal lobe (MTA) is being used as a criterion to support a diagnosis of Alzheimer's disease (AD). There are several structural neuroimaging approaches for quantifying MTA, including semiquantitative visual rating scales, volumetry (3D), planimetry (2D), and linear measures (1D). Current applications of structural neuroimaging in Alzheimer's disease clinical trials (ADCTs) incorporate it as a tool for improving the selection of subjects for enrollment or for stratification, for tracking disease progression, or providing evidence of target engagement for new therapeutic agents. It may also be used as a surrogate marker, providing evidence of disease-modifying effects. However, despite the widespread use of volumetric magnetic resonance imaging (MRI) in ADCTs, there are some important challenges and limitations, such as difficulties in the interpretation of results, limitations in translating results into clinical practice, and reproducibility issues, among others. Solutions to these issues may arise from other methodologies that are able to link the results of volumetric MRI from trials with conventional MRIs performed in routine clinical practice (linear or planimetric methods). Also of potential benefit are automated volumetry, using indices for comparing the relative rate of atrophy of different regions instead of absolute rates of atrophy, and combining structural neuroimaging with other biomarkers. In this review, authors present the existing structural neuroimaging approaches for MTA quantification. They then discuss solutions to the limitations of the different techniques as well as the current challenges of the field. Finally, they discuss how the current advances in AD neuroimaging can help AD diagnosis.

  11. 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

    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 blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological...

  12. Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome

    Directory of Open Access Journals (Sweden)

    Natalie Neale

    2018-01-01

    Full Text Available People with Down syndrome (DS develop Alzheimer's disease (AD at higher rates and a younger age of onset compared to the general population. As the average lifespan of people with DS is increasing, AD is becoming an important health concern in this group. Neuroimaging is becoming an increasingly useful tool in understanding the pathogenesis of dementia development in relation to clinical symptoms. Furthermore, neuroimaging has the potential to play a role in AD diagnosis and monitoring of therapeutics. This review describes major recent findings from in vivo neuroimaging studies analysing DS and AD via ligand-based positron emission tomography (PET, [18F] fluorodeoxyglucose (FDG-PET, structural magnetic resonance imaging (sMRI, and diffusion tensor imaging (DTI. Electroencephalography (EEG and retinal imaging are also discussed as emerging modalities. The review is organized by neuroimaging method and assesses the relationship between cognitive decline and neuroimaging changes. We find that amyloid accumulation seen on PET occurs prior to dementia onset, possibly as a precursor to the atrophy and white matter changes seen in MRI studies. Future PET studies relating tau distribution to clinical symptoms will provide further insight into the role this protein plays in dementia development. Brain activity changes demonstrated by EEG and metabolic changes seen via FDG-PET may also follow predictable patterns that can help track dementia progression. Finally, newer approaches such as retinal imaging will hopefully overcome some of the limitations of neuroimaging and allow for detection of dementia at an earlier stage.

  13. Random Forest Algorithm for the Classification of Neuroimaging Data in Alzheimer's Disease: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Alessia Sarica

    2017-10-01

    Full Text Available Objective: Machine learning classification has been the most important computational development in the last years to satisfy the primary need of clinicians for automatic early diagnosis and prognosis. Nowadays, Random Forest (RF algorithm has been successfully applied for reducing high dimensional and multi-source data in many scientific realms. Our aim was to explore the state of the art of the application of RF on single and multi-modal neuroimaging data for the prediction of Alzheimer's disease.Methods: A systematic review following PRISMA guidelines was conducted on this field of study. In particular, we constructed an advanced query using boolean operators as follows: (“random forest” OR “random forests” AND neuroimaging AND (“alzheimer's disease” OR alzheimer's OR alzheimer AND (prediction OR classification. The query was then searched in four well-known scientific databases: Pubmed, Scopus, Google Scholar and Web of Science.Results: Twelve articles—published between the 2007 and 2017—have been included in this systematic review after a quantitative and qualitative selection. The lesson learnt from these works suggest that when RF was applied on multi-modal data for prediction of Alzheimer's disease (AD conversion from the Mild Cognitive Impairment (MCI, it produces one of the best accuracies to date. Moreover, the RF has important advantages in terms of robustness to overfitting, ability to handle highly non-linear data, stability in the presence of outliers and opportunity for efficient parallel processing mainly when applied on multi-modality neuroimaging data, such as, MRI morphometric, diffusion tensor imaging, and PET images.Conclusions: We discussed the strengths of RF, considering also possible limitations and by encouraging further studies on the comparisons of this algorithm with other commonly used classification approaches, particularly in the early prediction of the progression from MCI to AD.

  14. The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, Michael W. [Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States); Veitch, Dallas P. [Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States); Aisen, Paul S. [Univ. of Southern California, San Diego, CA (United States); Beckett, Laurel A. [Univ. of California, Davis, CA (United States); Cairns, Nigel J. [Washington Univ. School of Medicine, St. Louis, MO (United States); Green, Robert C. [Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Harvey, Danielle [Univ. of California, Davis, CA (United States); Jack, Clifford R. [Mayo Clinic, Rochester, MN (United States); Jagust, William [Univ. of California, Berkeley, CA (United States); Morris, John C. [Univ. of Southern California, San Diego, CA (United States); Petersen, Ronald C. [Mayo Clinic, Rochester, MN (United States); Salazar, Jennifer [Univ. of Southern California, San Diego, CA (United States); Saykin, Andrew J. [Indiana Univ. School of Medicine, Indianapolis, IN (United States); Shaw, Leslie M. [Eli Lilly and Company, Indianapolis, IN (United States); Toga, Arthur W. [Univ. of Southern California, Los Angeles, CA (United States); Trojanowski, John Q. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    2016-12-05

    Overall, the goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. Finally, ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.

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

    International Nuclear Information System (INIS)

    Li, Tie-Qiang; Wahlund, Lars-Olof

    2011-01-01

    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)

  16. 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)

  17. Alzheimer's Disease Cerebrospinal Fluid and Neuroimaging Biomarkers: Diagnostic Accuracy and Relationship to Drug Efficacy.

    Science.gov (United States)

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

    Widely researched Alzheimer's disease (AD) biomarkers include in vivo brain imaging with PET and MRI, imaging of amyloid plaques, and biochemical assays of Aβ 1 - 42, total tau, and phosphorylated tau (p-tau-181) in cerebrospinal fluid (CSF). In this review, we critically evaluate these biomarkers and discuss their clinical utility for the differential diagnosis of AD. Current AD biomarker tests are either highly invasive (requiring CSF collection) or expensive and labor-intensive (neuroimaging), making them unsuitable for use in the primary care, clinical office-based setting, or to assess drug efficacy in clinical trials. In addition, CSF and neuroimaging biomarkers continue to face challenges in achieving required sensitivity and specificity and minimizing center-to-center variability (for CSF-Aβ 1 - 42 biomarkers CV = 26.5% ; http://www.alzforum.org/news/conference-coverage/paris-standardization-hurdle-spinal-fluid-imaging-markers). Although potentially useful for selecting patient populations for inclusion in AD clinical trials, the utility of CSF biomarkers and neuroimaging techniques as surrogate endpoints of drug efficacy needs to be validated. Recent trials of β- and γ-secretase inhibitors and Aβ immunization-based therapies in AD showed no significant cognitive improvements, despite changes in CSF and neuroimaging biomarkers. As we learn more about the dysfunctional cellular and molecular signaling processes that occur in AD, and how these processes are manifested in tissues outside of the brain, new peripheral biomarkers may also be validated as non-invasive tests to diagnose preclinical and clinical AD.

  18. The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Salazar, Jennifer; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

    2017-05-01

    The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  19. Tensor-based morphometry with mappings parameterized by stationary velocity fields in Alzheimer's disease neuroimaging initiative.

    Science.gov (United States)

    Bossa, Matías Nicolás; Zacur, Ernesto; Olmos, Salvador

    2009-01-01

    Tensor-based morphometry (TBM) is an analysis technique where anatomical information is characterized by means of the spatial transformations between a customized template and observed images. Therefore, accurate inter-subject non-rigid registration is an essential prerrequisite. Further statistical analysis of the spatial transformations is used to highlight some useful information, such as local statistical differences among populations. With the new advent of recent and powerful non-rigid registration algorithms based on the large deformation paradigm, TBM is being increasingly used. In this work we evaluate the statistical power of TBM using stationary velocity field diffeomorphic registration in a large population of subjects from Alzheimer's Disease Neuroimaging Initiative project. The proposed methodology provided atrophy maps with very detailed anatomical resolution and with a high significance compared with results published recently on the same data set.

  20. Neuroimaging and Other Biomarkers for Alzheimer's Disease: The Changing Landscape of Early Detection

    Science.gov (United States)

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    The goal of this review is to provide an overview of biomarkers for Alzheimer's disease (AD), with emphasis on neuroimaging and cerebrospinal fluid (CSF) biomarkers. We first review biomarker changes in patients with late-onset AD, including findings from studies using structural and functional magnetic resonance imaging (MRI), advanced MRI techniques (diffusion tensor imaging, magnetic resonance spectroscopy, perfusion), positron emission tomography with fluorodeoxyglucose, amyloid tracers, and other neurochemical tracers, and CSF protein levels. Next, we evaluate findings from these biomarkers in preclinical and prodromal stages of AD including mild cognitive impairment (MCI) and pre-MCI conditions conferring elevated risk. We then discuss related findings in patients with dominantly inherited AD. We conclude with a discussion of the current theoretical framework for the role of biomarkers in AD and emergent directions for AD biomarker research. PMID:23297785

  1. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features

    NARCIS (Netherlands)

    Ossenkoppele, R.; Pijnenburg, Y.A.L.; Perry, D.C.; Cohn-Sheehy, B.I.; Scheltens, N.M.E.; Vogel, J.W.; Kramer, J.H.; van der Vlies, A.E.; La Joie, R.; Rosen, H.J.; van der Flier, W.M.; Grinberg, L.T.; Rozemuller, A.J.M.; Huang, E.J.; van Berckel, B.N.M.; Miller, B.L.; Barkhof, F.; Jagust, W.J.; Scheltens, P.; Seeley, W.W.; Rabinovici, G.D.

    2015-01-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical,

  2. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

    Science.gov (United States)

    Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

    2011-09-01

    Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

  3. Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review.

    Science.gov (United States)

    Ruan, Qingwei; D'Onofrio, Grazia; Sancarlo, Daniele; Bao, Zhijun; Greco, Antonio; Yu, Zhuowei

    2016-05-16

    Neuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer's disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), with emphasis on neuroimaging biomarkers. A systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non-demented subjects. Selection criteria included: 1) age ≥ 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments. Seventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia. The panel of noninvasive neuroimaging-biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

  4. Neuroimaging in dementia and Alzheimer's disease: Current protocols and practice in the Republic of Ireland

    International Nuclear Information System (INIS)

    Kelly, I.; Butler, M.-L.; Ciblis, A.; McNulty, J.P.

    2016-01-01

    Introduction: Neuroimaging plays an essential supportive role in the diagnosis of dementia, assisting in establishing the dementia subtype(s). This has significant value in both treatment and care decisions and has important implications for prognosis. This study aims to explore the development and nature of neuroimaging protocols currently used in the assessment of dementia and Alzheimer's disease (AD). Methods: An online questionnaire was designed and distributed to lead radiography personnel working in computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) departments (n = 94) in both hospital-based and out-patient imaging centres in the Republic of Ireland. Results: Response rates for each modality ranged from 42 to 44%. CT, MRI, and PET were used to specifically diagnose dementia or AD by 43%, 40% and 50% of responding centres respectively. Of these, dementia-specific neuroimaging protocols were utilised in 33%, 50% and 100% of CT, MRI and PET centres respectively, with the remainder using either standard or other non-specific protocols. Both radiologists and clinical specialist radiographers participated in the development of the majority of protocols. The Royal College of Radiologists (RCR) guidelines were most commonly referenced as informing protocol development, however, none of the MRI respondents were able to identify any guidelines used to inform MR protocol development. Conclusion: Currently there is no consensus in Ireland on optimal dementia/AD neuroimaging protocols, particularly for PET and MRI. Similarly the use of validated and published guidelines to inform protocols is not universal. - Highlights: • We examined the nature of neuroimaging protocols for dementia and Alzheimer's disease in Ireland. • Dementia or Alzheimer's disease-specific protocols were used by between 33 and 100% of centres depending on modality. • Stated dementia-specific protocols were identical for CT whereas

  5. The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

    Science.gov (United States)

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2014-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

  6. Mapping longitudinal scientific progress, collaboration and impact of the Alzheimer's disease neuroimaging initiative.

    Directory of Open Access Journals (Sweden)

    Xiaohui Yao

    Full Text Available Alzheimer's disease neuroimaging initiative (ADNI is a landmark imaging and omics study in AD. ADNI research literature has increased substantially over the past decade, which poses challenges for effectively communicating information about the results and impact of ADNI-related studies. In this work, we employed advanced information visualization techniques to perform a comprehensive and systematic mapping of the ADNI scientific growth and impact over a period of 12 years.Citation information of ADNI-related publications from 01/01/2003 to 05/12/2015 were downloaded from the Scopus database. Five fields, including authors, years, affiliations, sources (journals, and keywords, were extracted and preprocessed. Statistical analyses were performed on basic publication data as well as journal and citations information. Science mapping workflows were conducted using the Science of Science (Sci2 Tool to generate geospatial, topical, and collaboration visualizations at the micro (individual to macro (global levels such as geospatial layouts of institutional collaboration networks, keyword co-occurrence networks, and author collaboration networks evolving over time.During the studied period, 996 ADNI manuscripts were published across 233 journals and conference proceedings. The number of publications grew linearly from 2008 to 2015, so did the number of involved institutions. ADNI publications received much more citations than typical papers from the same set of journals. Collaborations were visualized at multiple levels, including authors, institutions, and research areas. The evolution of key ADNI research topics was also plotted over the studied period.Both statistical and visualization results demonstrate the increasing attention of ADNI research, strong citation impact of ADNI publications, the expanding collaboration networks among researchers, institutions and ADNI core areas, and the dynamic evolution of ADNI research topics. The visualizations

  7. 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)....

  8. Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set.

    Science.gov (United States)

    Park, Ji Eun; Park, Bumwoo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Oh, Joo Young; Lee, Jae-Hong; Roh, Jee Hoon; Shim, Woo Hyun

    2017-01-01

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal ( p Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  9. Reference standard space hippocampus labels according to the European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative harmonized protocol: Utility in automated volumetry.

    Science.gov (United States)

    Wolf, Dominik; Bocchetta, Martina; Preboske, Gregory M; Boccardi, Marina; Grothe, Michel J

    2017-08-01

    A harmonized protocol (HarP) for manual hippocampal segmentation on magnetic resonance imaging (MRI) has recently been developed by an international European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative project. We aimed at providing consensual certified HarP hippocampal labels in Montreal Neurological Institute (MNI) standard space to serve as reference in automated image analyses. Manual HarP tracings on the high-resolution MNI152 standard space template of four expert certified HarP tracers were combined to obtain consensual bilateral hippocampus labels. Utility and validity of these reference labels is demonstrated in a simple atlas-based morphometry approach for automated calculation of HarP-compliant hippocampal volumes within SPM software. Individual tracings showed very high agreement among the four expert tracers (pairwise Jaccard indices 0.82-0.87). Automatically calculated hippocampal volumes were highly correlated (r L/R  = 0.89/0.91) with gold standard volumes in the HarP benchmark data set (N = 135 MRIs), with a mean volume difference of 9% (standard deviation 7%). The consensual HarP hippocampus labels in the MNI152 template can serve as a reference standard for automated image analyses involving MNI standard space normalization. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  10. Defining multivariate normative rules for healthy aging using neuroimaging and machine learning: an application to Alzheimer's disease.

    Science.gov (United States)

    Andrade de Oliveira, Ailton; Carthery-Goulart, Maria Teresa; Oliveira Júnior, Pedro Paulo de Magalhães; Carrettiero, Daniel Carneiro; Sato, João Ricardo

    2015-01-01

    Neuroimaging techniques combined with computational neuroanatomy have been playing a role in the investigation of healthy aging and Alzheimer's disease (AD). The definition of normative rules for brain features is a crucial step to establish typical and atypical aging trajectories. To introduce an unsupervised pattern recognition method; to define multivariate normative rules of neuroanatomical measures; and to propose a brain abnormality index. This study was based on a machine learning approach (one class classification or novelty detection) to neuroanatomical measures (brain regions, volume, and cortical thickness) extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s database. We applied a ν-One-Class Support Vector Machine (ν-OC-SVM) trained with data from healthy subjects to build an abnormality index, which was compared with subjects diagnosed with mild cognitive impairment and AD. The method was able to classify AD subjects as outliers with an accuracy of 84.3% at a false alarm rate of 32.5%. The proposed brain abnormality index was found to be significantly associated with group diagnosis, clinical data, biomarkers, and future conversion to AD. These results suggest that one-class classification may be a promising approach to help in the detection of disease conditions. Our findings support a framework considering the continuum of brain abnormalities from healthy aging to AD, which is correlated with cognitive impairment and biomarkers measurements.

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

    Science.gov (United States)

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

    2016-03-22

    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.

  12. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Alzheimer disease

    Science.gov (United States)

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

  14. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford; Jagust, William; Trojanowski, John Q; Shaw, Leslie M; Saykin, Andrew J; Green, Robert C; Harvey, Danielle; Toga, Arthur W; Friedl, Karl E; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2014-06-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  15. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

    Science.gov (United States)

    Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ 2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  16. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    Science.gov (United States)

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. © 2015 Japanese Society of Neuropathology.

  17. Update on the MRI Core of the Alzheimer's Disease Neuroimaging Initiative

    Science.gov (United States)

    Jack, Clifford R; Bernstein, Matt A; Borowski, Bret J; Gunter, Jeffrey L; Fox, Nick C; Thompson, Paul M; Schuff, Norbert; Krueger, Gunnar; Killiany, Ronald J; DeCarli, Charles S; Dale, Anders M; Weiner, Michael W

    2010-01-01

    Functions of the ADNI MRI core fall into three categories: (1) those of the central MRI core lab at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data, and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present (“ADNI-GO”) and future (“ADNI-2”, if funded) MRI protocol will be to maintain MRI methodological consistency in previously enrolled “ADNI-1” subjects who are followed longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor specific pilot sub-studies of arterial spin labeling perfusion, resting state functional connectivity and diffusion tensor imaging. One each of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multi-center (but single vendor) setting for these three emerging MRI applications. PMID:20451869

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

    Science.gov (United States)

    Schröder, Johannes; Pantel, Johannes

    2016-01-30

    As a characteristic feature of Alzheimer's disease (AD) hippocampal atrophy (HA) can be demonstrated in the majority of patients by using neuroimaging techniques in particular magnetic resonance imaging (MRI). Hippocampal atrophy is associated with declarative memory deficits and can also be associated with changes of adjacent medial temporal substructures such as the parahippocampal gyrus or the the entorhinal cortex. Similar findings are present in patients with mild cognitive impairment (MCI) albeit to a lesser extent. While these finding facilitate the diagnostic process in patients with clinical suspicious AD, the metric properties of hippocampal atrophy for delineating healthy aging from MCI and mild AD still appear to be rather limited; as such it is not sufficient to establish the diagnosis of AD (and even more so of MCI). This limitation partly refers to methodological issues and partly to the fact that hippocampal tissue integrity is subject to various pathogenetic influences other than AD. Moreover,the effects of hippocampal atrophy on the behavioral level (e.g. cognitive deficits) are modulated by the individual's cognitive reserve. From a clinical standpoint these observations are in line with the hypothesis that the onset and course of AD is influenced by a number of peristatic factors which are partly conceptualized in the concepts of brain and/or cognitive reserve. These complex interactions have to be considered when using the presence of hippocampal atrophy in the routine diagnostic procedure of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. 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 ...

  20. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    International Nuclear Information System (INIS)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun; Lee, Jae Hong; Roh, Jee Hoon

    2017-01-01

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease

  1. Improved diagnostic accuracy of Alzheimer's disease by combining regional cortical thickness and default mode network functional connectivity: Validated in the Alzheimer's disease neuroimaging initiative set

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Park, Bum Woo; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Jung; Oh, Joo Young; Shim, Woo Hyun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jae Hong; Roh, Jee Hoon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To identify potential imaging biomarkers of Alzheimer's disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this model's diagnostic accuracy in a validation set. Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimer's Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimer's disease.

  2. Alzheimer's disease.

    Science.gov (United States)

    Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria

    2016-07-30

    Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research. Copyright © 2016 Elsevier Ltd. All

  3. Apathy in Alzheimer's disease

    OpenAIRE

    Nobis, L; Husain, M

    2017-01-01

    Apathy is the most common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The presence of apathy has been related to greater caregiver distress, decreased quality of life, and increased morbidity. Here we review the most recent studies on this neuropsychiatric syndrome, focusing on prevalence, impact on quality of life, behavioural and neuroimaging studies, and treatment options. The results of some investigations on the behavioural and neuroanatomical profile of apathy in...

  4. Tensor-based morphometry as a neuroimaging biomarker for Alzheimer's disease: an MRI study of 676 AD, MCI, and normal subjects.

    Science.gov (United States)

    Hua, Xue; Leow, Alex D; Parikshak, Neelroop; Lee, Suh; Chiang, Ming-Chang; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2008-11-15

    In one of the largest brain MRI studies to date, we used tensor-based morphometry (TBM) to create 3D maps of structural atrophy in 676 subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy elderly controls, scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using inverse-consistent 3D non-linear elastic image registration, we warped 676 individual brain MRI volumes to a population mean geometric template. Jacobian determinant maps were created, revealing the 3D profile of local volumetric expansion and compression. We compared the anatomical distribution of atrophy in 165 AD patients (age: 75.6+/-7.6 years), 330 MCI subjects (74.8+/-7.5), and 181 controls (75.9+/-5.1). Brain atrophy in selected regions-of-interest was correlated with clinical measurements--the sum-of-boxes clinical dementia rating (CDR-SB), mini-mental state examination (MMSE), and the logical memory test scores - at voxel level followed by correction for multiple comparisons. Baseline temporal lobe atrophy correlated with current cognitive performance, future cognitive decline, and conversion from MCI to AD over the following year; it predicted future decline even in healthy subjects. Over half of the AD and MCI subjects carried the ApoE4 (apolipoprotein E4) gene, which increases risk for AD; they showed greater hippocampal and temporal lobe deficits than non-carriers. ApoE2 gene carriers--1/6 of the normal group--showed reduced ventricular expansion, suggesting a protective effect. As an automated image analysis technique, TBM reveals 3D correlations between neuroimaging markers, genes, and future clinical changes, and is highly efficient for large-scale MRI studies.

  5. Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary Report.

    Science.gov (United States)

    Weiner, Michael W; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M; Aisen, Paul S; Petersen, Ronald C; Tosun, Duygu; Veitch, Dallas P; Jack, Clifford R; Decarli, Charles; Saykin, Andrew J; Grafman, Jordan; Neylanthe, Thomas C

    2017-06-01

    Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural MRI and amyloid PET scans. We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau PET scans will provide more information in the future.

  6. Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer's disease neuroimaging initiative study.

    Science.gov (United States)

    Shi, Jie; Leporé, Natasha; Gutman, Boris A; Thompson, Paul M; Baxter, Leslie C; Caselli, Richard J; Wang, Yalin

    2014-08-01

    The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database-the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T(2) test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Copyright © 2014 Wiley Periodicals, Inc.

  7. Effects of HLA-DRB1/DQB1 Genetic Variants on Neuroimaging in Healthy, Mild Cognitive Impairment, and Alzheimer's Disease Cohorts.

    Science.gov (United States)

    Wang, Zi-Xuan; Wang, Hui-Fu; Tan, Lin; Liu, Jinyuan; Wan, Yu; Sun, Fu-Rong; Tan, Meng-Shan; Tan, Chen-Chen; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2017-07-01

    Alzheimer's disease (AD) is the most common form of dementia and exhibits a considerable level of heritability. Previous association studies gave evidence for the associations of HLA-DRB1/DQB1 alleles with AD. However, how and when the gene variants in HLA-DRB1/DQB1 function in AD pathogenesis has yet to be determined. Here, we firstly investigated the association of gene variants in HLA-DRB1/DQB1 alleles and AD related brain structure on magnetic resonance imaging (MRI) in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We selected hippocampus, subregion, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). Twelve SNPs in HLA-DRB1/DQB1 were identified in the dataset following quality control measures. In the total group hybrid population analysis, our study (rs35445101, rs1130399, and rs28746809) were associated with the smaller baseline volume of the left posterior cingulate and rs2854275 was associated with the larger baseline volume of the left posterior cingulate. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) sub-group analysis, and two risk loci (rs35445101 and rs1130399) were also the smaller baseline volume of the left posterior cingulate in (NC) sub-group analysis. Our study suggested that HLA-DRB1/DQB1 gene variants appeared to modulate the alteration of the left posterior cingulate volume, hence modulating the susceptibility of AD.

  8. Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

    Science.gov (United States)

    Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

    2017-07-01

    The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Quiz: Alzheimer's Disease

    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. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study.

    Science.gov (United States)

    Dubois, Bruno; Epelbaum, Stephane; Nyasse, Francis; Bakardjian, Hovagim; Gagliardi, Geoffroy; Uspenskaya, Olga; Houot, Marion; Lista, Simone; Cacciamani, Federica; Potier, Marie-Claude; Bertrand, Anne; Lamari, Foudil; Benali, Habib; Mangin, Jean-François; Colliot, Olivier; Genthon, Remy; Habert, Marie-Odile; Hampel, Harald

    2018-04-01

    Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on 18 F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on 18 F-fluorodeoxyglucose ( 18 F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and 18 F-FDG and 18 F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type. From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1-8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid

  11. A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer's Disease: Preliminary Results from a Neuroimaging Study.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Paquet, Nancy; Dionne, Isabelle J; Imbeault, Hélène; Langlois, Francis; Croteau, Etienne; Tremblay, Sébastien; Fortier, Mélanie; Matte, J Jacques; Lacombe, Guy; Fülöp, Tamás; Bocti, Christian; Cunnane, Stephen C

    2017-01-01

    Aerobic training has some benefits for delaying the onset or progression of Alzheimer's disease (AD). Little is known about the implication of the brain's two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2-3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 μmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop-color naming test (-10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01). In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement.

  12. Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia.

    Science.gov (United States)

    Trzepacz, Paula T; Yu, Peng; Sun, Jia; Schuh, Kory; Case, Michael; Witte, Michael M; Hochstetler, Helen; Hake, Ann

    2014-01-01

    In this study we compared Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimer's dementia using data from the Alzheimer's Disease Neuroimaging Initiative cohort. Numeric neuroimaging variables generated by the Alzheimer's Disease Neuroimaging Initiative-funded laboratories for each neuroimaging modality along with apolipoprotein-E genotype (n = 29) were analyzed. Performance of these biomarkers for predicting conversion from MCI to Alzheimer's dementia at 2 years was evaluated in 50 late amnestic MCI subjects, 20 of whom converted. Multivariate modeling found that among individual modalities, MRI had the highest predictive accuracy (67%) which increased by 9% to 76% when combined with PIB-PET, producing the highest accuracy among any biomarker combination. Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Alzheimer's Disease Information Page

    Science.gov (United States)

    ... the National Library of Medicine’s MedlinePlus Alzheimer's Disease Alzheimer's Caregivers × What research is being done? The National Institute ... the National Library of Medicine’s MedlinePlus Alzheimer's Disease Alzheimer's Caregivers See More About Research The National Institute of ...

  14. Neuroimaging abnormalities in Griscelli's disease

    International Nuclear Information System (INIS)

    Sarper, Nazan; Akansel, Guer; Aydogan, Metin; Gedikbasi, Demet; Babaoglu, Kadir; Goekalp, Ayse Sevim

    2002-01-01

    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.)

  15. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Alzheimer disease Alzheimer disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alzheimer disease is a degenerative disease of the brain ...

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: Download ... worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease ...

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: Download ... about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease ...

  18. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    Science.gov (United States)

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: Download ... spending. Take action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, ...

  20. 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....

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... health and long-term care costs. worried about memory loss? KNOW THE 10 SIGNS Alzheimer's Disease Facts ... Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, ...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  3. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full ... all ages are living with Alzheimer's dementia in 2018. This number includes an estimated 5.5 million ...

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Alzheimer's >> Home Text size: A A A 2017 Alzheimer's Disease Facts and Figures Download the Full Report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family ...

  5. Alzheimer's disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition.

    Science.gov (United States)

    Leow, Alex D; Yanovsky, Igor; Parikshak, Neelroop; Hua, Xue; Lee, Suh; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Britson, Paula J; Gunter, Jeffrey L; Ward, Chadwick P; Borowski, Bret; Shaw, Leslie M; Trojanowski, John Q; Fleisher, Adam S; Harvey, Danielle; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2009-04-15

    Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

  6. Inter-rater variability of visual interpretation and comparison with quantitative evaluation of11C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study.

    Science.gov (United States)

    Yamane, Tomohiko; Ishii, Kenji; Sakata, Muneyuki; Ikari, Yasuhiko; Nishio, Tomoyuki; Ishii, Kazunari; Kato, Takashi; Ito, Kengo; Senda, Michio

    2017-05-01

    The aim of this study was to assess the inter-rater variability of the visual interpretation of 11 C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). A total of 162 11 C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate correct diagnosis when evaluating images of low amyloid deposition.

  7. Hirayama disease: diagnostic essentials in neuroimaging.

    Science.gov (United States)

    Kapetanakis, Stylianos; Chourmouzi, Danae; Terzoudi, Aikaterini; Georgiou, Nikiforos; Giovannopoulou, Eirini

    2017-12-01

    A 22-year-old male presented with progressive muscular weakness of the upper extremities. MRI of the cervical spine established the final diagnosis of Hirayama disease (HD). HD is a rare disease with benign progress. Neurologists and radiologists should be aware of the specific neuroimaging signs of this rare clinical entity.

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... pocket spending. Take action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history ... State The 2017 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease ...

  9. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... THE 10 SIGNS Alzheimer's Disease Facts in Each State The 2018 Alzheimer's Disease Facts and Figures report ... on the impact of this disease in every state across the nation. Click below to see the ...

  10. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease in every ...

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and Figures report ... on the impact of this disease in every state across the nation. Click below to see the ...

  12. Anosognosia in Alzheimer's disease: A neuropsychological approach

    OpenAIRE

    Zilli, Bárbara Bomfim Caiado de Castro; Damasceno, Benito Pereira

    2007-01-01

    Abstract Anosognosia is often found in Alzheimer´s disease (AD), but its relationship with cognitivebehavioral changes is not well established. Objective: To verify if anosognosia is related to cognitive-behavioral disturbances, and to regional brain dysfunction as evaluated by neuroimaging. Methods: We included AD patients with Mini-Mental State Examination (MMSE) scores of 12 through 24, and Clinical Dementia Rating (CDR) scores of 1 or 2. Dementia diagnosis was based on DSM-IV and NINCDS...

  13. Epidemiology of Alzheimer Disease

    Science.gov (United States)

    Mayeux, Richard; Stern, Yaakov

    2012-01-01

    The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease. PMID:22908189

  14. Alzheimer\\'s Disease: Yesterday, Today, Tomorrow

    Directory of Open Access Journals (Sweden)

    Farid Fadaei

    2007-04-01

    Full Text Available Alzheimer's disease is the most common and well - known cause of dementia, as a progressive, irreversible brain disorder that affects cognitive function, personality, thought, perception and behaviour. Alzheimer's disease is the fourth leading cause of death in western countries. Interesting to know that this disease was unknown in medical community till 100 years ago and had no name. Dr. Alois Alzheimer, a German psychiatrist was the person who suspected the presence of this new illness and by succinct clinical, neuroanatomic, and neuropathologic examination of some cases; including the first known case of this disease- a woman named Auguste Deter- documented it. In further Emil Kraepe1inby knowing about the cases that Dr. Alzheimer reported, and another reports of this disease that were published in the first decade of the twentieth century, set the name of Alzbeimer on this new disease. Descriptions of Dr. Alzheimer and Kraepelin are the same as the present day descriptions of this disease. Electron microscopy, quantitative morphology and modem biochemistry emerging in the second half of the twentieth century opened a new era in dementia research with description of the ultra structure and biochemistry of senileplaques and neuronfibrillary tangles, the major disease markers of Alzheimer's disease. Basic research gave insight into the molecular genetics and pathophysiology of Alzheimers disease and based on the biochemical findings, new pharmacological treatment options were opened. The future attempts will probably be concentrated on the prevention of this disease. Oxidative stress, excessive transition metal ions, and misfolded / aggregated proteins and inflammation are among the probable causes of Alzheimer's disease and the future research will focus on their better understanding and prevention of their occurrence. As the last word, stem cells grafts that in animals have led to remarkable improvement of brain function may also be a

  15. Behavioral and Neuroimaging Evidence for Facial Emotion Recognition in Elderly Korean Adults with Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

    Science.gov (United States)

    Park, Soowon; Kim, Taehoon; Shin, Seong A; Kim, Yu Kyeong; Sohn, Bo Kyung; Park, Hyeon-Ju; Youn, Jung-Hae; Lee, Jun-Young

    2017-01-01

    Background: Facial emotion recognition (FER) is impaired in individuals with frontotemporal dementia (FTD) and Alzheimer's disease (AD) when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in FER performance in patients with dementia. Purpose: The purpose of this study was to identify the performance profiles of six facial emotions (i.e., fear, anger, disgust, sadness, surprise, and happiness) and neutral faces measured among Korean healthy control (HCs), and those with mild cognitive impairment (MCI), AD, and FTD. Additionally, the neuroanatomical correlates of facial emotions were investigated. Methods: A total of 110 (33 HC, 32 MCI, 32 AD, 13 FTD) older adult participants were recruited from two different medical centers in metropolitan areas of South Korea. These individuals underwent an FER test that was used to assess the recognition of emotions or absence of emotion (neutral) in 35 facial stimuli. Repeated measures two-way analyses of variance were used to examine the distinct profiles of emotional recognition among the four groups. We also performed brain imaging and voxel-based morphometry (VBM) on the participants to examine the associations between FER scores and gray matter volume. Results: The mean score of negative emotion recognition (i.e., fear, anger, disgust, and sadness) clearly discriminated FTD participants from individuals with MCI and AD and HC [ F (3,106) = 10.829, p < 0.001, η 2 = 0.235], whereas the mean score of positive emotion recognition (i.e., surprise and happiness) did not. A VBM analysis showed negative emotions were correlated with gray matter volume of anterior temporal regions, whereas positive emotions were related to gray matter volume of fronto-parietal regions. Conclusion: Impairment of negative FER in patients with FTD is cross-cultural. The discrete neural correlates of FER indicate that emotional

  16. Neuroimaging of Parkinson's disease: Expanding views.

    Science.gov (United States)

    Weingarten, Carol P; Sundman, Mark H; Hickey, Patrick; Chen, Nan-kuei

    2015-12-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Buerger, K.; Teipel, S.J.; Hampel, H.

    2000-01-01

    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.) [de

  18. Mitophagy and Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kerr, Jesse S.; Adriaanse, Bryan A.; Greig, Nigel H.

    2017-01-01

    Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged...

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's ... date on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  20. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... of biomarkers for Alzheimer's disease is making it possible to detect Alzheimer's disease and provide an accurate diagnosis earlier than at any other time in history. In addition to providing significant medical, emotional and ...

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... number of important benefits to diagnosed individuals, their caregivers and loved ones, as well as society as a whole. The development of biomarkers for Alzheimer's disease is making it possible to detect Alzheimer's disease ...

  2. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Dementia is one of the costliest conditions to society. Total payments in 2017 for all individuals with ... earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the ...

  3. Alzheimer's Disease Facts and Figures

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    Full Text Available ... States will develop the disease every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is ... read our security and privacy policy . Plan ahead Get help and support I have Alzheimer's I am ...

  4. Alzheimer's Disease Facts and Figures

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    Full Text Available ... scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute ... priority. It has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, ...

  5. Alzheimer's Disease Facts and Figures

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    Full Text Available ... ALZ | Research | Professionals | We Can Help | Join the Cause alz.org >> Living with Alzheimer's >> Home Text size: ... disease every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is the sixth-leading cause ...

  6. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Alzheimer's disease is making it possible to detect Alzheimer's disease and provide an accurate diagnosis earlier than at any other time in history. ... to make decisions and share their wishes. Early diagnosis, even ... who will get Alzheimer's disease were diagnosed when they had mild cognitive ...

  7. [How to define Alzheimer's disease].

    Science.gov (United States)

    Poncet, Michel

    2011-09-01

    Alzheimer's disease, which was considered to be a rare disease in subjects aged under 65 until the seventies/eighties, has become a very common disease affecting mostly older subjects. Many consider that it is important to review the meaning of the eponym "Alzheimer's disease", and a revolution, quite literally, is likely to occur. The role of vascular lesions in the onset of dementias among older subjects is widely acknowledged; considering those dementias as Alzheimer's disease may have negative consequences for patient management. Indeed, vascular lesions can be prevented and treated, while Alzheimer's lesions cannot. It may be justified to use "Alzheimer syndrome" instead of "Alzheimer's disease" when vascular risk factors and, all the more so, vascular lesions are present. Significant progress has been made in the understanding of the pathological proteins involved in Alzheimer's disease, as well as their effects on neurons and synapses. However, the etiology of the disease is still unknown, except in the rare hereditary cases, and there is no cure for Alzheimer's disease at present. Clinical research is progressing, and diagnostic criteria for the pre-dementia stage of Alzheimer's disease were suggested. In France, the outstanding Alzheimer plan 2008-2012 should play an important role in enhancing the understanding of Alzheimer's disease, Alzheimer's syndromes and related disorders.

  8. Inflammation and Alzheimer's disease

    NARCIS (Netherlands)

    Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G. M.; Cooper, N. R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B. L.; Finch, C. E.; Frautschy, S.; Griffin, W. S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I. R.; McGeer, P. L.; O'Banion, M. K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; van Muiswinkel, F. L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T.

    2000-01-01

    Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical

  9. Inter-rater variability of visual interpretation and comparison with quantitative evaluation of 11C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study

    International Nuclear Information System (INIS)

    Yamane, Tomohiko; Ishii, Kenji; Sakata, Muneyuki; Ikari, Yasuhiko; Nishio, Tomoyuki; Ishii, Kazunari; Kato, Takashi; Ito, Kengo; Senda, Michio

    2017-01-01

    The aim of this study was to assess the inter-rater variability of the visual interpretation of 11 C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). A total of 162 11 C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR. Inter-rater agreement was almost perfect in 11 C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate

  10. Inter-rater variability of visual interpretation and comparison with quantitative evaluation of {sup 11}C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Tomohiko [Saitama Medical University Saitama International Center, Department of Nuclear Medicine, Hidaka (Japan); Institute of Biomedical Research and Innovation, Division of Molecular Imaging, Kobe (Japan); Tokyo Metropolitan Institute of Gerontology, Team for Neuroimaging Research, Tokyo (Japan); Ishii, Kenji; Sakata, Muneyuki [Tokyo Metropolitan Institute of Gerontology, Team for Neuroimaging Research, Tokyo (Japan); Ikari, Yasuhiko; Nishio, Tomoyuki [Institute of Biomedical Research and Innovation, Division of Molecular Imaging, Kobe (Japan); Research Association for Biotechnology, Tokyo (Japan); Ishii, Kazunari [Kinki University Hospital, Department of Radiology, Osaka, Sayama (Japan); Kato, Takashi; Ito, Kengo [National Center for Geriatrics and Gerontology, Department of Brain Science and Molecular Imaging, Obu (Japan); Senda, Michio [Institute of Biomedical Research and Innovation, Division of Molecular Imaging, Kobe (Japan); Collaboration: J-ADNI Study Group

    2017-05-15

    The aim of this study was to assess the inter-rater variability of the visual interpretation of {sup 11}C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). A total of 162 {sup 11}C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR. Inter-rater agreement was almost perfect in {sup 11}C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may

  11. Eye Movements in Alzheimer?s Disease

    OpenAIRE

    Molitor, Robert J.; Ko, Philip C.; Ally, Brandon A.

    2015-01-01

    A growing body of literature has investigated changes in eye movements as a result of Alzheimer?s disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We d...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we ... on the latest news and advances in Alzheimer's treatments, care and research. Get tips for living with ...

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... meaning that they care not only for an aging parent, but also for children under age 18. ... diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Help | Join the Cause alz.org >> Alzheimer's & Dementia >> Home Text size: A A A 2018 Alzheimer's Disease ... people who receive adult day services and nursing home care. Take action. Become an advocate SPECIAL REPORT: ...

  15. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET INVOLVED. Join ...

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... existing cases of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the disease every 33 seconds. GET ...

  17. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    ... A A A Share Plus on Google Plus Alzheimer's & Dementia alz.org | IHaveAlz Overview What Is Dementia ... chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected by Down ...

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

  19. Alzheimer's Disease Facts and Figures

    Science.gov (United States)

    ... Dementia >> Home Text size: A A A 2018 Alzheimer's Disease Facts and Figures Download the full report: ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help ...

  20. [Palliative care and Alzheimer disease].

    Science.gov (United States)

    Lopez-Tourres, F; Lefebvre-Chapiro, S; Fétéanu, D; Trivalle, C

    2009-06-01

    Although end-of-life care is a relatively common option for patients with terminal cancer, it has become available only recently for patients with Alzheimer's disease. Alzheimer's disease is a chronic process of gradual deterioration of cognitive ability and the resulting deficits in activities of daily living. The chronic disease course of Alzheimer's disease gives to the clinician the opportunity to look ahead and plan for the final stages of care. This article presents a review of palliative care interventions for patients with Alzheimer's disease and other dementias. End-of-life care for individuals with end-stage Alzheimer's disease is increasingly important because of the increasing number of patients with this disease. However, there are barriers to providing high-quality end-of-life care. Currently, palliative care is not optimal for Alzheimer's patients. Health care systems and clinicians should make efforts to improve the suffering of patients with this disease and their caregivers.

  1. Tacrine for Alzheimer's disease.

    Science.gov (United States)

    Qizilbash, N; Birks, J; López-Arrieta, J; Lewington, S; Szeto, S

    2000-01-01

    Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. However, the efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to use many of the published results in a combined

  2. Oligodendrocytes and Alzheimer's disease.

    Science.gov (United States)

    Cai, Zhiyou; Xiao, Ming

    2016-01-01

    Extensive evidence has indicated that the breakdown of myelin is associated with Alzheimer's disease (AD) since the vulnerability of oligodendrocytes under Alzheimer's pathology easily induces the myelin breakdown and the loss of the myelin sheath which might be the initiating step in the changes of the earliest stage of AD prior to appearance of amyloid and tau pathology. Considerable research implicated that beta-amyloid (Aβ)-mediated oligodendrocyte dysfunction and myelin breakdown may be via neuroinflammation, oxidative stress and/or apoptosis. It also seems that the oligodendrocyte dysfunction is triggered by the formation of neurofibrillary tangles (NFTs) through inflammation and oxidative stress as the common pathophysiological base. Impaired repair of oligodendrocyte precursor cells (OPCs) might possibly enhance the disease progress under decreased self-healing ability from aging process and pathological factors including Aβ pathology and/or NFTs. Thus, these results have suggested that targeting oligodendrocytes may be a novel therapeutic intervention for the prevention and treatment of AD.

  3. [Calcium hypothesis of Alzheimer disease].

    Science.gov (United States)

    Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

    2012-01-01

    Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

  4. Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease.

    Science.gov (United States)

    Chong, Joanna Su Xian; Liu, Siwei; Loke, Yng Miin; Hilal, Saima; Ikram, Mohammad Kamran; Xu, Xin; Tan, Boon Yeow; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian; Zhou, Juan

    2017-11-01

    Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our

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

    DEFF Research Database (Denmark)

    Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho

    2011-01-01

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

  6. Vascular care in patients with Alzheimer's disease with cerebrovascular lesions-a randomized clinical trial

    NARCIS (Netherlands)

    Richard, Edo; Kuiper, Roy; Dijkgraaf, Marcel G. W.; van Gool, Willem A.

    2009-01-01

    OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... which Alzheimer's disease is placed in the same category as other chronic diseases, such as ... report contains data on the impact of this disease in every state across the ...

  8. Selegiline for Alzheimer's disease.

    Science.gov (United States)

    Birks, J; Flicker, L

    2003-01-01

    Alzheimer's disease is the most common cause of dementia in older people accounting for some 60% of cases with late-onset cognitive deterioration. It is now thought that several neurotransmitter dysfunctions are involved from an early stage in the pathogenesis of Alzheimer's disease-associated cognitive decline. The efficacy of selegiline for symptoms of Alzheimer's disease remains controversial and is reflected by its low rate of prescription and the lack of approval by several regulatory authorities in Europe and elsewhere. Reasons for this uncertainty involve the modest overall effects observed in some trials, the lack of benefit observed in several trials, the use of cross-over designs which harbour methodological problems in a disease like dementia and the difficulty in interpreting results from trials when a variety of measurement scales are used to assess outcomes. The objective of this review is to assess whether or not selegiline improves the well-being of patients with Alzheimer's disease. The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'selegiline', 'l-deprenyl', "eldepryl" and "monamine oxidase inhibitor-B". MEDLINE, PsycLIT and EMBASE electronic databases were searched with the above terms in addition to using the group strategy (see group details) to limit the searches to randomised controlled trials. All unconfounded, double-blind, randomised controlled trials in which treatment with selegiline was administered for more than a day and compared to placebo in patients with dementia. An individual patient data meta-analysis of selegiline, Wilcock 2002 provides much of the data that are available for this review. Seven studies provided individual patient data and this was pooled with summary statistics from the published papers of the other nine studies. Where possible, intention-to-treat data were used but usually the meta analyses were restricted to completers' data (data on people who

  9. and late onset Alzheimer's disease

    African Journals Online (AJOL)

    Yomi

    2012-03-15

    Mar 15, 2012 ... Alzheimer's disease (AD) is a prevalent disorder and the most common cause of dementia in elderly populations. Genetic and environmental factors together play a role in developing late onset. Alzheimer's disease (LOAD). According to the recent published papers, ACE is one of the candidate.

  10. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available 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 provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  11. [Alzheimer's disease and olfaction].

    Science.gov (United States)

    Naudin, Marine; Mondon, Karl; Atanasova, Boriana

    2013-09-01

    Although olfactory disorders are not at the forefront of the clinical description of Alzheimer's disease (AD), they are common and often overlooked by clinicians and by patients who are largely unaware of their deficits. The past 30 years, the literature has shown early olfactory deficits in AD that is spreading across the olfactory spectrum with disease worsening. Partial overlap between brain areas implies both in olfaction and AD - especially limbic system - motivating these researches. This study describes olfactory parameters and tests using to investigate peripheral (odor threshold) and central (hedonicity, familiarity, intensity, discrimination, identification, olfactory memory) levels. Besides, this article takes an inventory of olfactory disorders in AD including odor threshold, discrimination, identification and olfactory memory capacities with controversial results observed in literature. At last, we discuss which type of olfactory dysfunction could have a clinical interest.

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... home care. Take action. Become an advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early ... State The 2018 Alzheimer's Disease Facts and Figures report contains data on the impact of this disease ...

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease is the only top 10 cause of death in the United States that cannot be prevented, ... Alzheimer's disease is the sixth-leading cause of death in the United States, and the fifth-leading ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. ... irrevocable disability occurs. LEARN ABOUT OUR COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State ...

  15. Is Alzheimer's disease a homogeneous disease entity?

    Science.gov (United States)

    Korczyn, Amos D

    2013-10-01

    The epidemic proportions of dementia in old age are a cause of great concern for the medical profession and the society at large. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, and vascular dementia (VaD) as being the second. This dichotomous view of a primary neurodegenerative disease as opposed to a disorder where extrinsic factors cause brain damage led to separate lines of research in these two entities. New biomarkers, particularly the introduction of modern neuroimaging and cerebrospinal fluid changes, have, in recent years, helped to identify anatomical and chemical changes of VaD and of AD. Nevertheless, there is a substantial difference between the two entities. While it is clear that VaD is a heterogeneous entity, AD is supposed to be a single disorder. Nobody attempts to use CADASIL as a template to develops treatment for sporadic VaD. On the other hand, early-onset AD is used to develop therapy for sporadic AD. This paper will discuss the problems relating to this false concept and its consequences.

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 million ... 200,000 individuals are under age 65 and have younger-onset Alzheimer's. One in 10 people age ...

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, ...

  18. Alzheimer's Disease: The Death of the Disease.

    Science.gov (United States)

    McBroom, Lynn W.

    1987-01-01

    Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…

  19. Neuroimaging in pre-motor Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Thomas R. Barber

    2017-01-01

    Full Text Available The process of neurodegeneration in Parkinson's disease begins long before the onset of clinical motor symptoms, resulting in substantial cell loss by the time a diagnosis can be made. The period between the onset of neurodegeneration and the development of motoric disease would be the ideal time to intervene with disease modifying therapies. This pre-motor phase can last many years, but the lack of a specific clinical phenotype means that objective biomarkers are needed to reliably detect prodromal disease. In recent years, recognition that patients with REM sleep behaviour disorder (RBD are at particularly high risk of future parkinsonism has enabled the development of large prodromal cohorts in which to investigate novel biomarkers, and neuroimaging has generated some of the most promising results to date. Here we review investigations undertaken in RBD and other pre-clinical cohorts, including modalities that are well established in clinical Parkinson's as well as novel imaging methods. Techniques such as high resolution MRI of the substantia nigra and functional imaging of Parkinsonian brain networks have great potential to facilitate early diagnosis. Further longitudinal studies will establish their true value in quantifying prodromal neurodegeneration and predicting future Parkinson's.

  20. Galantamine for Alzheimer's disease.

    Science.gov (United States)

    Olin, J; Schneider, L

    2001-01-01

    Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer

  1. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    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

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

    Science.gov (United States)

    Cohen, Gene D.

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

  3. Rivastigmine for Alzheimer's disease.

    Science.gov (United States)

    Birks, Jacqueline S; Chong, Lee Yee; Grimley Evans, John

    2015-09-22

    Alzheimer's disease is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and lower risk of adverse effects have since been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA. To determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 2 March 2015 using the terms: Rivastigmine OR  exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources. We included all unconfounded, double-blind, randomised, controlled trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two formulations of rivastigmine were compared. One review author (JSB) applied the study selection criteria, assessed the quality of studies and extracted data. A total of 13 trials met the inclusion criteria of the review. The trials had a duration of between 12 and 52 weeks. The older trials tested a capsule form with a dose of up to 12 mg/day. Trials

  4. Alzheimer disease and anesthesia.

    Science.gov (United States)

    Inan, Gözde; Özköse Satirlar, Zerrin

    2015-01-01

    Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained inportance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. As the population is aging, many elderly patients will need to be anesthetized, and maybe some were already anesthetized before they were diagnosed. Exposure to anesthetics has been demonstrated to promote pathogenesis of AD in both in vitro and in vivo studies. However, to date, there have not been any clinical trials to address a link between exposure to GA and the development of AD in humans. Therefore, before making any conclusions we need further studies, but we should be aware of the potential risks and take cautions with vulnerable elderly patients.

  5. Aluminum and Alzheimer's Disease.

    Science.gov (United States)

    Colomina, Maria Teresa; Peris-Sampedro, Fiona

    2017-01-01

    Aluminum (Al) is one of the most extended metals in the Earth's crust. Its abundance, together with the widespread use by humans, makes Al-related toxicity particularly relevant for human health.Despite some factors influence individual bioavailability to this metal after oral, dermal, or inhalation exposures, humans are considered to be protected against Al toxicity because of its low absorption and efficient renal excretion. However, several factors can modify Al absorption and distribution through the body, which may in turn progressively contribute to the development of silent chronic exposures that may lately trigger undesirable consequences to health. For instance, Al has been recurrently shown to cause encephalopathy, anemia, and bone disease in dialyzed patients. On the other hand, it remains controversial whether low doses of this metal may contribute to developing Alzheimer's disease (AD), probably because of the multifactorial and highly variable presentation of the disease.This chapter primarily focuses on two key aspects related to Al neurotoxicity and AD, which are metabolic impairment and iron (Fe) alterations. We discuss sex and genetic differences as a plausible source of bias to assess risk assessment in human populations.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change...... in 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...

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Facts and Figures report contains data on the impact of this disease in every state across the nation. Click below to see the effect that Alzheimer's is having in your state. Read ...

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. The development and validation of Alzheimer's disease ...

  9. [Proceeding memory in Alzheimer's disease].

    Science.gov (United States)

    Arroyo-Anlló, Eva Ma; Chamorro-Sánchez, Jorge; Díaz-Marta, Juan Poveda; Gil, Roger

    2013-01-01

    Procedural learning can acquire or develop skills through performance and repetition of a task unconsciously or unintentionally. Procedural skills are considered as the cornerstone in the neuropsychological rehabilitation to promote the autonomy of patients with brain damage, as those with Alzheimer's disease. This review presents data about procedural skills in Alzheimer's disease. Over the past three decades, we have found 40 articles studying various procedural skills in the Alzheimer's disease: motor, perceptual-motor, cognitive, perceptual-cognitive and those developed through serial reaction-time paradigm. We analyzed every study evaluating a procedural skill, indicating the used task and preservation or no preservation of procedural learning. Overall, most of the papers published describe conservation of learning procedures or relatively conserved in Alzheimer's disease, which could be used to promote patient autonomy.

  10. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... every 33 seconds. GET INVOLVED. Join the cause Mortality Alzheimer's disease is the only top 10 cause ... This dramatic rise includes more than four-fold increases both in government spending under Medicare and Medicaid ...

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the ... proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, ...

  12. 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 ...

  13. Alzheimer's disease and intelligence.

    Science.gov (United States)

    Yeo, R A; Arden, R; Jung, R E

    2011-06-01

    A significant body of evidence has accumulated suggesting that individual variation in intellectual ability, whether assessed directly by intelligence tests or indirectly through proxy measures, is related to risk of developing Alzheimer's disease (AD) in later life. Important questions remain unanswered, however, such as the specificity of risk for AD vs. other forms of dementia, and the specific links between premorbid intelligence and development of the neuropathology characteristic of AD. Lower premorbid intelligence has also emerged as a risk factor for greater mortality across myriad health and mental health diagnoses. Genetic covariance contributes importantly to these associations, and pleiotropic genetic effects may impact diverse organ systems through similar processes, including inefficient design and oxidative stress. Through such processes, the genetic underpinnings of intelligence, specifically, mutation load, may also increase the risk of developing AD. We discuss how specific neurobiologic features of relatively lower premorbid intelligence, including reduced metabolic efficiency, may facilitate the development of AD neuropathology. The cognitive reserve hypothesis, the most widely accepted account of the intelligence-AD association, is reviewed in the context of this larger literature.

  14. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

    Scheibel, A.B.; Wechsler, A.F.; Brazier, M.A.B.

    1986-01-01

    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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  16. Anosognosia in Alzheimer´s disease: A neuropsychological approach

    OpenAIRE

    Zilli, Bárbara Bomfim Caiado de Castro; Damasceno, Benito Pereira

    2007-01-01

    Abstract Anosognosia is often found in Alzheimer´s disease (AD), but its relationship with cognitivebehavioral changes is not well established. Objective: To verify if anosognosia is related to cognitive-behavioral disturbances, and to regional brain dysfunction as evaluated by neuroimaging. Methods: We included AD patients with Mini-Mental State Examination (MMSE) scores of 12 through 24, and Clinical Dementia Rating (CDR) scores of 1 or 2. Dementia diagnosis was based on DSM-IV and NINCDS...

  17. Nutritional supplementation for Alzheimer's disease?

    Science.gov (United States)

    Shea, Thomas B; Remington, Ruth

    2015-03-01

    Evidence for the benefit of nutrition in Alzheimer's disease continues to accumulate. Many studies with individual vitamins or supplements show marginal, if any, benefit. However, new findings with combinatorial formulations demonstrate improvement in cognitive performance and behavioral difficulties that accompany Alzheimer's disease. Herein, we review some of the most recent clinical advances and summarize supportive preclinical studies. We present novel positive effects on Alzheimer's disease derived from diet, trace elements, vitamins and supplements. We discuss the inherent difficulty in conducting nutritional studies because of the variance in participants' nutritional history, versus pharmacological interventions in which participants are naive to the intervention. We examine the evidence that epigenetics play a role in Alzheimer's disease and how nutritional intervention can modify the key epigenetic events to maintain or improve cognitive performance. Overall consideration of the most recent collective evidence suggests that the optimal approach for Alzheimer's disease would seem to combine early, multicomponent nutritional approaches (a Mediterranean-style diet, multivitamins and key combinatorial supplements), along with lifestyle modifications such as social activity and mental and physical exercise, with ultimate addition of pharmacological agents when warranted.

  18. Insulin and Alzheimer disease: type 3 diabetes?

    Directory of Open Access Journals (Sweden)

    Andrés Jagua Gualdrón

    2007-01-01

    Full Text Available Alzheimer Disease is a neurodegenerative disease of central nervous system whose incidence will increase in next years. Recent investigations relate alzheimer with insulin signaling defects in neurons. Is alzheimer Disease a type 3 diabetes? In this communication write a brief article about evidences from this alzheimer‘s disease model.

  19. 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.

  20. CT study in Alzheimer's disease

    International Nuclear Information System (INIS)

    Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji

    1983-01-01

    Cerebral atrophy on CT was studied in 18 patients with clinically diagnosed Alzheimer's disease and in 14 healthy age-matched subjects as the control. The patients with Alzheimer's disease were divided into three groups of Stages I, Ii and III, according to their clinical symptoms. The study of the measurement method disclosed that the computerized measurement involving calculation of the number of pixels contained within the range of the designated CT numbers is liable to produce errors for the determination of the subarachnoid spaces and the ventricles with calcified colloid plexus. Therefor, for the present study was the method adopted, in which the subarachnoid spaces and the ventricles are measured based on the number of pixels contained in the region of interest by tracing them on the display monitor. Then, both Subarachnoid Space Volume Index (SVI) and Ventricle Volume Index (VVI) were calculated as the indices for cortical atrophy and ventricular dilatation in a slice through the level of the foramen interventriculare Monroi and other three successive ones through upper regions. Cerebral atrophy observed on CT in Alzheimer patients is attributable to Alzheimer's disease processes, rather than to physiological aging of the brain. The degree of the atrophy increases in proportion to the clinical stage, and cortical atrophy is apparent even at Stage I, whereas ventricular dilatation becomes pronounced at later stage. CT is one of effective clinical tests for the diagnosis of Alzheimer's disease. (J.P.N.)

  1. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

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

    2013-01-01

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

  2. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    Science.gov (United States)

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

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

    Science.gov (United States)

    Leroux, Charles

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

  4. 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.

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... An estimated 5.5 million Americans of all ages have Alzheimer's disease. Of the estimated 5.5 ... in 2017, an estimated 5.3 million are age 65 and older and approximately 200,000 individuals ...

  6. Caregiver Response to Alzheimer's Disease.

    Science.gov (United States)

    Novak, Mark; Guest, Carol

    1989-01-01

    Examined correlates of caregiver burden among 30 caregivers of Alzheimer's disease patients. Results revealed no significant correlation between length of time a caregiver had given care to a particular patient and the caregiver's subjective feelings of caregiver burden. Found significant, moderate correlation between caregiver burden and patient…

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... get Alzheimer's disease were diagnosed in the mild cognitive impairment (MCI) stage — before dementia — it would collectively save $7 trillion to $7.9 trillion in health and long-term care costs. worried about memory ...

  8. Head trauma and Alzheimer's disease

    NARCIS (Netherlands)

    Nandoe, Rishi D. S.; Scheltens, Philip; Eikelenboom, Piet

    2002-01-01

    The authors describe a case of a 55 year old woman who was diagnosed with Alzheimer's disease 1.5 years after a car accident in which she experienced a mild concussion. Extensive history taking disclosed no cognitive changes prior to the car accident. The case is discussed in view of the

  9. Genome instability in Alzheimer disease

    DEFF Research Database (Denmark)

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

    2017-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Autosomal dominant, familial AD (fAD) is very rare and caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) genes. The pathogenesis...

  10. Cerebral imaging revealing Alzheimer's disease

    International Nuclear Information System (INIS)

    2011-01-01

    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)

  11. Pharmacologic management of Alzheimer disease.

    Science.gov (United States)

    Downey, Deborah

    2008-02-01

    Although the diagnosis of AD can be devastating, treatment options exist that can slow the disease's progression and allow patients to continue performing ADLs, thereby improving the quality of life for both patient and caregiver. Research is ongoing, and it is estimated by the Alzheimer's Association that finding a treatment that could delay onset by only 5 years could reduce the number of individuals with AD by nearly 50% over the next 50 years (Alzheimer's Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an important part of a total approach to caring for patients and families affected by AD.

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.

  13. [Nutritional status in Alzheimer's disease].

    Science.gov (United States)

    Machado, Jacqueline; Caram, Carmen Lucia Barreto; Frank, Andrea Abdala; Soares, Eliane de Abreu; Laks, Jerson

    2009-01-01

    To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. Subjects of both genders (n=40) diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary profiles were surveyed. Of the total, 65% were female. More than 70% were capable of accomplishing daily activities by themselves. Subjects were eutrophic with a statistically significant difference of the arm circumference between the mild and moderate groups. As for illnesses secondary to Alzheimer's, 52% of the elderly presented hypertension, followed by arthrosis type alterations (17%). The mean consumption of energy and macronutrients in the elderly classified as mild dementia was of 1645 kcal, distributed in 53.7% of carbohydrate, 17.5% of proteins or 0.9 g/kg and 28.8% of lipids. For those classified as moderate dementia it was of 1482 kcal, distributed in 59.3% of carbohydrate, 16.1% of proteins and 24.6% of lipids. In this descriptive study of elderly outpatients with mild and moderate Alzheimer's disease, most presented a nutritional status of eutrophy, with adequate dietary intake of carbohydrates, proteins, lipids and vitamin C, but with low dietary intake of vitamin E.

  14. Alzheimer's disease: studies of diagnosis and therapy

    NARCIS (Netherlands)

    J.J. Claus (Jules Johan)

    1993-01-01

    textabstractDespite tremendous recent advances in the clinical neurology, neurobiology and epidemiology of Alzheimer's disease, the cause as well as its treatment remains as much a mystery today as when it was first described in 1907 by Alois Alzheimer.' Alzheimer's disease, the most common type

  15. 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.

  16. Behavioral syndromes in Alzheimer's disease.

    Science.gov (United States)

    Devanand, D P; Brockington, C D; Moody, B J; Brown, R P; Mayeux, R; Endicott, J; Sackeim, H A

    1992-01-01

    The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

  17. 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.

  18. Neuroimaging of Parkinson’s Disease: Expanding views

    Science.gov (United States)

    Weingarten, Carol P.; Sundman, Mark H.; Hickey, Patrick; Chen, Nankuei

    2015-01-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. PMID:26409344

  19. Functional Neuroimaging of Motor Control inParkinson’s Disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Structural Neuroimaging Genetics Interactions in Alzheimer’s Disease

    Science.gov (United States)

    Moon, Seok Woo; Dinov, Ivo D.; Kim, Jaebum; Zamanyan, Alen; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2016-01-01

    This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for subjects participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Eight hundred and eight ADNI subjects were identified and divided into three groups: those with Alzheimer’s Disease (AD), those with mild cognitive impairment (MCI), and asymptomatic normal control (NC) group. Two hundred of the subjects qualified for AD diagnosis at the baseline; three hundred and eighty-three had MCI; and 225 were included in the NC group. The structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the Global Shape Analysis (GSA) Pipeline workflow. We obtained 80 SNPs using Plink analysis via the Pipeline environment. In the AD cohort, rs2137962 was significantly associated with changes in left and right hippocampi and bilaterally in parahippocampal gyri, and rs1498853, rs288503, and rs288496 were significantly associated with hippocampi bilaterally, the right parahippocampal gyrus, and left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with right caudate and right fusiform gyrus, and rs2075650 (TOMM40) was significantly associated with right caudate, rs1334496 and rs4829605 were significantly associated with right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML) and rs1052242 (PML)] was significantly associated with the both hippocampi and both insular cortex and rs4899412 (RGS6) was significantly associated with caudate related biomarkers. We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 808 subjects in terms of neuroimaging genetics. These results illustrate some of the neuroimaging-genetics associations between the AD, MCI and NC cohorts. PMID:26444770

  1. Depression and Alzheimer's Disease

    Science.gov (United States)

    ... help them—and you—feel better. As the caregiver of a person who has Alzheimer’s disease, you must also take care of yourself. If ... that is given to a patient who has Alzheimer’s disease in order to provide relief for the caregiver. Look or ask the doctor for caregiver support ...

  2. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... is a not-for-profit 501(c)(3) organization. Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our ... Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research.

  3. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... In My Area | Alzheimer's & Dementia | Life with ALZ | Research | Professionals | We Can Help | Join the Cause alz. ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  6. 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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Henrique Cerqueira Guimarães

    2008-06-01

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

  9. 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.

  10. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available 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 provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  11. Mathematical model on Alzheimer's disease.

    Science.gov (United States)

    Hao, Wenrui; Friedman, Avner

    2016-11-18

    Alzheimer disease (AD) is a progressive neurodegenerative disease that destroys memory and cognitive skills. AD is characterized by the presence of two types of neuropathological hallmarks: extracellular plaques consisting of amyloid β-peptides and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. The disease affects 5 million people in the United States and 44 million world-wide. Currently there is no drug that can cure, stop or even slow the progression of the disease. If no cure is found, by 2050 the number of alzheimer's patients in the U.S. will reach 15 million and the cost of caring for them will exceed $ 1 trillion annually. The present paper develops a mathematical model of AD that includes neurons, astrocytes, microglias and peripheral macrophages, as well as amyloid β aggregation and hyperphosphorylated tau proteins. The model is represented by a system of partial differential equations. The model is used to simulate the effect of drugs that either failed in clinical trials, or are currently in clinical trials. Based on these simulations it is suggested that combined therapy with TNF- α inhibitor and anti amyloid β could yield significant efficacy in slowing the progression of AD.

  12. Alzheimer's disease: a practical, psychological approach.

    Science.gov (United States)

    Powell, L S

    1985-01-01

    Alzheimer's Disease affects approximately two million people. It is a crippling, organic brain disorder that causes loss of recent memory, intellectual deterioration, unpredictable behavioral changes, and personality deterioration. The fourth leading cause of death among the elderly, it also affects younger people. The disease has two victims, the Alzheimer patient and the caregiver. Caregivers often experience shame, embarrassment, denial, frustration, anger, depression, and guilt as they care for an Alzheimer patient. This paper provides information about the disease and it's manifestations, along with practical suggestions to help both the Alzheimer patient and the caregiver.

  13. Alzheimer's disease: synapses gone cold

    Directory of Open Access Journals (Sweden)

    Hyman Bradley T

    2011-08-01

    Full Text Available Abstract Alzheimer's disease (AD is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ, the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP and facilitate long-term depression (LTD, electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.

  14. Brainstem morphological changes in Alzheimer's disease.

    Science.gov (United States)

    Lee, Ji Han; Ryan, John; Andreescu, Carmen; Aizenstein, Howard; Lim, Hyun Kook

    2015-05-06

    As brainstem nuclei are interconnected with several cortical structures and regulate several autonomic, cognitive, and behavioral functions, it might be important to place the brainstem within an important pathologic core in the progression of Alzheimer's disease (AD). Although there have been several postmortem studies reporting neuropathological alterations of the brainstem in AD, there has been no in-vivo structural neuroimaging study of the brainstem in the patients with AD. The aim of this study was to investigate differences in the brainstem volume and shape between patients with AD and elderly normal controls. Fifty AD patients (the Clinical Dementia Rating Scale ≥ 1) and 50 normal controls were recruited, and the brainstem volumes and deformations were compared between the AD and the controls. Patients with AD showed significant total volume [(mean ± SD) 21007 ± 1640 mm] reduction in the brainstem compared with the controls [(mean ± SD) 22530 ± 1750 mm] (Pfalse discovery rate corrected Pmemory impairment, sleep, and emotional disturbance in AD. However, further longitudinal studies might be needed to confirm these findings.

  15. 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 ...

  16. Eye movements in Alzheimer's disease.

    Science.gov (United States)

    Molitor, Robert J; Ko, Philip C; Ally, Brandon A

    2015-01-01

    A growing body of literature has investigated changes in eye movements as a result of Alzheimer's disease (AD). When compared to healthy, age-matched controls, patients display a number of remarkable alterations to oculomotor function and viewing behavior. In this article, we review AD-related changes to fundamental eye movements, such as saccades and smooth pursuit motion, in addition to changes to eye movement patterns during more complex tasks like visual search and scene exploration. We discuss the cognitive mechanisms that underlie these changes and consider the clinical significance of eye movement behavior, with a focus on eye movements in mild cognitive impairment. We conclude with directions for future research.

  17. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

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

    2012-01-01

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

  18. Solving the puzzle of Alzheimer disease.

    Science.gov (United States)

    Uriri-Glover, Johannah; McCarthy, Marianne; Cesarotti, Evelyn

    2012-09-10

    Managing patients with dementia and Alzheimer disease can be a challenge. Often, families and caregivers ask clinicians about the latest treatments. This article summarizes the latest evidence-based practice related to pharmacologic and nonpharmacologic management of patients with Alzheimer disease.

  19. Turning principles into practice in Alzheimer's disease

    NARCIS (Netherlands)

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

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

  20. Amyloid imaging in prodromal Alzheimer's disease

    NARCIS (Netherlands)

    Ossenkoppele, R.; van Berckel, B.N.M.; Prins, N.D.

    2011-01-01

    Patients with mild cognitive impairment are at an increased risk of progression to Alzheimer's disease. However, not all patients with mild cognitive impairment progress, and it is difficult to accurately identify those patients who are in the prodromal stage of Alzheimer's disease. In a recent

  1. WITHDRAWN: Tacrine for Alzheimer's disease.

    Science.gov (United States)

    Qizilbash, N; Birks, J; Lopez Arrieta, J; Lewington, S; Szeto, S

    2007-07-18

    Tacrine is one of the first drugs to be widely marketed for the loss of memory and intellectual decline in Alzheimer's disease, often accompanied by abnormal behaviour and physical decline. The alleged success of tacrine in the treatment of these symptoms has been heralded as confirmation of the cholinergic theory of Alzheimer's disease. The efficacy of tacrine for symptoms of dementia remains controversial. This is reflected by the low rate of prescription of tacrine in countries where it is approved and the lack of approval by several regulatory authorities in Europe and elsewhere. The uncertainty about the efficacy of tacrine is due to the difficulties in interpretation of the results from the clinical trials. The reasons for this are the small effects of tacrine compared to placebo for all outcomes; the high incidence of adverse events; the lack of benefit observed in several trials; the use of cross-over designs and their associated methodological problems in a disease like dementia; the use of different measurement scales to assess outcome in different trials; and the problem of high dropout rates. To determine the clinical efficacy of tacrine for the symptoms of Alzheimer's disease. The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine' and 'THA' (see the Group's search strategy for full details). All unconfounded, double-blind, randomized trials in which treatment with tacrine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. This review produced no clear results. The results were compatible with tacrine producing improvement, no change or even harm for those with Alzheimer's disease. It was not possible to

  2. Alzheimer's Disease Facts and Figures

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    Full Text Available ... and older (10 percent) has Alzheimer's dementia. Almost two-thirds of Americans with Alzheimer's are women. Older ... 34 percent) is age 65 or older. Approximately two-thirds of caregivers are women; more specifically, over ...

  3. Alzheimer's Disease Facts and Figures

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    Full Text Available ... elderly people who receive adult day services and nursing home care. Take action. Become an advocate SPECIAL ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  4. Alzheimer's Disease Facts and Figures

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    Full Text Available ... advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early diagnosis of Alzheimer's provides a number ... a researcher Message boards Get the facts 10 warning signs & symptoms What is dementia What is Alzheimer's ...

  5. Alzheimer's Disease Facts and Figures

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    Full Text Available ... and social benefits and facilitating participation in important clinical trials, early diagnosis enables individuals to prepare legal, ... news and advances in Alzheimer's treatments, care and research. Get tips for living with Alzheimer's as well ...

  6. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Share the facts: Quick Facts Prevalence Mortality Caregivers Cost Special Report Alzheimer's in each state Quick Facts Share the facts: Prevalence The number of Americans living with Alzheimer's is growing — and growing fast. An ...

  7. Alzheimer's Disease Facts and Figures

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    Full Text Available ... to have Alzheimer's or other dementias as older whites. Hispanics are about one and one-half times ... to have Alzheimer's or other dementias as older whites. As the number of older Americans grows rapidly, ...

  8. Alzheimer's Disease Facts and Figures

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    Full Text Available ... older. It also is a leading cause of disability and poor health. Although deaths from other major ... c)(3) organization. Copyright © 2018 Alzheimer's Association ® . All rights reserved. Our vision is a world without Alzheimer's ...

  9. Alzheimer's Disease Facts and Figures

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    Full Text Available ... This number includes an estimated 5.5 million people age 65 and older and approximately 200,000 ... who have younger-onset Alzheimer's. One in 10 people age 65 and older (10 percent) has Alzheimer's ...

  10. Alzheimer's Disease Facts and Figures

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    Full Text Available ... newsletter Stay up-to-date on the latest news and advances in Alzheimer's treatments, care and research. ... to End Alzheimer's Become an advocate About Us | News | Events | Press | About this Site | Privacy Policy | Copyrights & ...

  11. Alzheimer's Disease Facts and Figures

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    Full Text Available ... state. Read past editions . Sign up for our e-newsletter Stay up-to-date on the latest ... Alzheimer's. First name: Last name: *Email: *Zip: Weekly E-Newsletter Breaking Research Updates The Alzheimer's Association does ...

  12. Alzheimer's Disease Facts and Figures

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    Full Text Available ... care. Caring for someone with Alzheimer's? Get Resources Cost to Nation Alzheimer's places a huge burden on the health care system, with annual costs exceeding a quarter of a trillion dollars. In ...

  13. Alzheimer's Disease Facts and Figures

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    Full Text Available ... were diagnosed in the mild cognitive impairment (MCI) stage — before dementia — it would collectively save $7 trillion ... symptoms What is dementia What is Alzheimer's 7 stages of Alzheimer's Treatments Contact us 24/7 Helpline: ...

  14. Alzheimer's Disease Facts and Figures

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    Full Text Available ... whites. Hispanics are about one and one-half times as likely to have Alzheimer's or other dementias ... with Alzheimer's or other dementias were over three times as great as payments for other Medicare beneficiaries. ...

  15. TREM2 Variants in Alzheimer's Disease

    Science.gov (United States)

    Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

    2013-01-01

    BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

  16. Humanin signal for Alzheimer's disease.

    Science.gov (United States)

    Matsuoka, Masaaki

    2011-01-01

    Despite a bulk of evidence supporting the idea that increased neurotoxic insults lead to Alzheimer's disease (AD), the possibility still remains that insufficiency of an endogenous defense system contributes to the disease progression. Humanin is a bioactive peptide that is likely to inhibit both neuronal death and dysfunction only related to AD by binding to a Humanin receptor on the cell-surface and by activating a STAT3-mediated signal, preventing the onset of dementia. A couple of recent studies presented evidence suggesting that the Humanin signal is decreased in neurons of AD patients. If this is the case, the restoration or activation of the Humanin signal in neurons may change the course of AD.

  17. [Alzheimer's disease: New therapeutic strategies].

    Science.gov (United States)

    Villegas, Sandra

    2015-07-20

    The rapid increase in prevalence rates of Alzheimer's disease means that treatments to prevent, stop or reverse this devastating disease are urgently needed. Despite advances in understanding its molecular pathology, there are no drugs that can halt its progression. This review takes a tour through phase 2, or higher studies, probing receptor agonist agents interfering with aggregation, inhibitors/modulators of secretases, lipid-lowering agents, and, finally and most extensively, immunotherapy. The fact that phase 3 studies with bapineuzumab and solaneuzumab have recently failed does not invalidate the potential of immunotherapy, as more information is available and new clinical trials are being initiated. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Neuropathological Alterations in Alzheimer Disease

    Science.gov (United States)

    Serrano-Pozo, Alberto; Frosch, Matthew P.; Masliah, Eliezer; Hyman, Bradley T.

    2011-01-01

    The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI. PMID:22229116

  19. Anosognosia in Alzheimer's disease: A neuropsychological approach.

    Science.gov (United States)

    Zilli, Bárbara Bomfim Caiado de Castro; Damasceno, Benito Pereira

    2007-01-01

    Anosognosia is often found in Alzheimer's disease (AD), but its relationship with cognitivebehavioral changes is not well established. To verify if anosognosia is related to cognitive-behavioral disturbances, and to regional brain dysfunction as evaluated by neuroimaging. We included AD patients with Mini-Mental State Examination (MMSE) scores of 12 through 24, and Clinical Dementia Rating (CDR) scores of 1 or 2. Dementia diagnosis was based on DSM-IV and NINCDS-ADRDA criteria.We used Self-Consciousness Questionnaire (SCQ) and Denial of Illness Scale (DIS), and following neuropsychological counterproofs: WAIS-R digit span, Rey auditory verbal learning, verbal fluency test (category: animals), Cummings' neuropsychiatric inventory (NPI) and Cornell scale for depression in dementia (CSDD). We studied 21 patients (12 men, 9 women) with AD (14 mild, 7 moderate), age 72.4±8.5 years, education 4.9± 4.2 years, and MMSE score 18.2±5. SCQ and DIS did not correlate to age, education, or regional cerebral perfusion defects, but they tended to correlate to disease duration (and only SCQ also to MMSE). SCQ and DIS were correlated neither to CSDD, NPI, CDR, nor to any neuropsychological test. Significant correlations were found between SCQ and DIS, as well as between SCQ domain of "moral judgment" and MMSE. SCQ and DIS were not correlated to age, education, disease duration, cognitive-behavioral measures, dementia severity, or regional cerebral perfusion defects, but were correlated to each other, suggesting SCQ and DIS evaluate similar mental functions.

  20. 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 ...

  1. Disease-modifying drugs in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ghezzi L

    2013-12-01

    Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

  2. Genetic Aspects of Alzheimer Disease

    Science.gov (United States)

    Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

    2011-01-01

    Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

  3. Predicting progression of Alzheimer's disease.

    Science.gov (United States)

    Doody, Rachelle S; Pavlik, Valory; Massman, Paul; Rountree, Susan; Darby, Eveleen; Chan, Wenyaw

    2010-02-23

    Clinicians need to predict prognosis of Alzheimer's disease (AD), and researchers need models of progression to develop biomarkers and clinical trials designs. We tested a calculated initial progression rate to see whether it predicted performance on cognition, function and behavior over time, and to see whether it predicted survival. We used standardized approaches to assess baseline characteristics and to estimate disease duration, and calculated the initial (pre-progression) rate in 597 AD patients followed for up to 15 years. We designated slow, intermediate and rapidly progressing groups. Using mixed effects regression analysis, we examined the predictive value of a pre-progression group for longitudinal performance on standardized measures. We used Cox survival analysis to compare survival time by progression group. Patients in the slow and intermediate groups maintained better performance on the cognitive (ADAScog and VSAT), global (CDR-SB) and complex activities of daily living measures (IADL) (P values < 0.001 slow versus fast; P values < 0.003 to 0.03 intermediate versus fast). Interaction terms indicated that slopes of ADAScog and PSMS change for the slow group were smaller than for the fast group, and that rates of change on the ADAScog were also slower for the intermediate group, but that CDR-SB rates increased in this group relative to the fast group. Slow progressors survived longer than fast progressors (P = 0.024). A simple, calculated progression rate at the initial visit gives reliable information regarding performance over time on cognition, global performance and activities of daily living. The slowest progression group also survives longer. This baseline measure should be considered in the design of long duration Alzheimer's disease clinical trials.

  4. Harmonized diagnostic criteria for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. 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.

  6. 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

  7. Alzheimer's disease: the dependency and care

    Directory of Open Access Journals (Sweden)

    Maria Amelia Ximenes

    2014-08-01

    Full Text Available Alzheimer's disease is the most common form of dementia among older people and has gradually increased with the aging population. Knowing Alzheimer's disease, the demand for care produced by the disease and its impact on the lives of family caregivers, give a sense of the scale of the problems faced in everyday life of families. This article is a literature review addresses these issues.  

  8. 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.

  9. Graphical Neuroimaging Informatics: Application to Alzheimer’s Disease

    Science.gov (United States)

    Bowman, Ian; Joshi, Shantanu H.; Greer, Vaughan

    2013-01-01

    The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer’s Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer’s Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN’s ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

  10. Multimodality imaging of Alzheimer disease and other neurodegenerative dementias.

    Science.gov (United States)

    Nasrallah, Ilya M; Wolk, David A

    2014-12-01

    Neurodegenerative diseases, such as Alzheimer disease, result in cognitive decline and dementia and are a leading cause of mortality in the growing elderly population. These progressive diseases typically have an insidious onset, with overlapping clinical features early in the disease course that make diagnosis challenging. The neurodegenerative diseases are associated with characteristic, although not completely understood, changes in the brain: abnormal protein deposition, synaptic dysfunction, neuronal injury, and neuronal death. Neuroimaging biomarkers-principally regional atrophy on structural MR imaging, patterns of hypometabolism on (18)F-FDG PET, and detection of cerebral amyloid plaque on amyloid PET--are able to evaluate the patterns of these abnormalities in the brain to improve early diagnosis and help predict the disease course. These techniques have unique strengths and synergies in multimodality evaluation of the patient with cognitive decline or dementia. This review discusses the key imaging biomarkers from MR imaging, (18)F-FDG PET, and amyloid PET; the imaging features of the most common neurodegenerative dementias; the role of various neuroimaging studies in differential diagnosis and prognosis; and some promising imaging techniques under development. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  11. Synaptic changes in Alzheimer's disease in vivo

    International Nuclear Information System (INIS)

    Mueller-Gaertner, H.W.

    1994-01-01

    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.) [de

  12. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  13. Active Vaccines for Alzheimer Disease Treatment.

    Science.gov (United States)

    Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

    2016-09-01

    Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  14. Global Data Sharing in Alzheimer Disease Research.

    Science.gov (United States)

    Ashish, Naveen; Bhatt, Priya; Toga, Arthur W

    2016-01-01

    Many investigators recognize the importance of data sharing; however, they lack the capability to share data. Research efforts could be vastly expanded if Alzheimer disease data from around the world was linked by a global infrastructure that would enable scientists to access and utilize a secure network of data with thousands of study participants at risk for or already suffering from the disease. We discuss the benefits of data sharing, impediments today, and solutions to achieving this on a global scale. We introduce the Global Alzheimer's Association Interactive Network (GAAIN), a novel approach to create a global network of Alzheimer disease data, researchers, analytical tools, and computational resources to better our understanding of this debilitating condition. GAAIN has addressed the key impediments to Alzheimer disease data sharing with its model and approach. It presents practical, promising, yet, data owner-sensitive data-sharing solutions.

  15. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  16. Education and the risk for Alzheimers disease

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  17. Alzheimer's Disease Facts and Figures

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    Full Text Available ... Nation Alzheimer's places a huge burden on the health care system, with annual costs exceeding a quarter of ... in out-of-pocket spending. The costs of health care and long-term care for individuals with Alzheimer's ...

  18. Alzheimer's Disease Facts and Figures

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    Full Text Available ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 million family and friends ... Plan ahead Get help and support I have Alzheimer's I am a caregiver I am a care professional I am a ...

  19. Alzheimer's Disease Facts and Figures

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    Full Text Available ... twice as high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help provided to ... Plan ahead Get help and support I have Alzheimer's I am a caregiver I am a care professional I am a ...

  20. Alzheimer's Disease Facts and Figures

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    Full Text Available ... 65 and have younger-onset Alzheimer's. One in 10 people age 65 and older (10 percent) has Alzheimer's dementia. Almost two-thirds of ... cause of death. It is the only top 10 cause of death that cannot be prevented, cured ...

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... as older whites. As the number of older Americans grows rapidly, so too will the numbers of new and existing cases of Alzheimer's. Today, someone in the United States develops Alzheimer's every 65 seconds. By mid-century, someone in the United States will develop the ...

  2. 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.

  3. Longitudinal score prediction for Alzheimer's disease based on ensemble correntropy and spatial-temporal constraint.

    Science.gov (United States)

    Lei, Baiying; Hou, Wen; Zou, Wenbin; Li, Xia; Zhang, Cishen; Wang, Tianfu

    2018-03-26

    Neuroimaging data has been widely used to predict clinical scores for automatic diagnosis of Alzheimer's disease (AD). For accurate clinical score prediction, one of the major challenges is high feature dimension of the imaging data. To address this issue, this paper presents an effective framework using a novel feature selection model via sparse learning. In contrast to previous approaches focusing on a single time point, this framework uses information at multiple time points. Specifically, a regularized correntropy with the spatial-temporal constraint is used to reduce the adverse effect of noise and outliers, and promote consistent and robust selection of features by exploring data characteristics. Furthermore, ensemble learning of support vector regression (SVR) is exploited to accurately predict AD scores based on the selected features. The proposed approach is extensively evaluated on the Alzheimer's disease neuroimaging initiative (ADNI) dataset. Our experiments demonstrate that the proposed approach not only achieves promising regression accuracy, but also successfully recognizes disease-related biomarkers.

  4. Ayurvedic Profiling of Alzheimer's Disease.

    Science.gov (United States)

    Bredesen, Dale E; Rao, Rammohan V

    2017-05-01

    Alzheimer's disease (AD) is an age-associated, progressive neurodegenerative disease that is characterized by severe memory loss, personality changes, and an overall decline in cognitive function. The cause of AD is not yet completely defined and efforts to find a cure for it have so far been disappointing. AD is one of the most significant health care problems nationally and globally. Recently, we described a personalized therapeutic approach called metabolic enhancement for neurodegeneration (MEND) that successfully reversed the cognitive decline in patients with early AD. The magnitude of the improvement was exceptional, providing testimony to the fact that a personalized and programmatic approach to cognitive decline is highly effective. Ayurveda is a personalized system of traditional medicine native to India and the Indian subcontinent. Although a direct reference to AD in the ancient Ayurvedic literature is missing, concepts including forgetfulness, memory loss, and brain cell loss have been described. Using the clinical information and the metabolic profiling of AD individuals we recently reported using the MEND program, we now describe in this commentary, 3 subtypes of AD based on the Ayurvedic interpretation. Ayurvedic profiling of patients with AD reveals 3 readily distinguishable subtypes, namely Vata, Pitta, and Krimi, which will prove useful in patients with cognitive decline and those at risk for such decline from the standpoint of specific subtype-based Ayurvedic intervention.

  5. Alzheimer's Disease and the Eye

    Directory of Open Access Journals (Sweden)

    Richard A. Armstrong

    2009-01-01

    Full Text Available Dementia, including Alzheimer's disease (AD, is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ in the form of senile plaques (SP and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT. A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA, colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP; and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

  6. Alzheimer's Disease and the Eye☆

    Science.gov (United States)

    Armstrong, Richard A.

    2010-01-01

    Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

  7. Molecular subtypes of Alzheimer's disease.

    Science.gov (United States)

    Di Fede, Giuseppe; Catania, Marcella; Maderna, Emanuela; Ghidoni, Roberta; Benussi, Luisa; Tonoli, Elisa; Giaccone, Giorgio; Moda, Fabio; Paterlini, Anna; Campagnani, Ilaria; Sorrentino, Stefano; Colombo, Laura; Kubis, Adriana; Bistaffa, Edoardo; Ghetti, Bernardino; Tagliavini, Fabrizio

    2018-02-19

    Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer's disease (AD), in which assemblies of amyloid β (Aβ) peptides accumulate in the brain in the form of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is characterized by distinct clinical and neuropathological phenotypes. Recent studies revealed that Aβ assemblies might have structural differences among AD brains and that such pleomorphic assemblies can correlate with distinct disease phenotypes. We found that in both sporadic and inherited forms of AD, amyloid aggregates differ in the biochemical composition of Aβ species. These differences affect the physicochemical properties of Aβ assemblies including aggregation kinetics, resistance to degradation by proteases and seeding ability. Aβ-amyloidosis can be induced and propagated in animal models by inoculation of brain extracts containing aggregated Aβ. We found that brain homogenates from AD patients with different molecular profiles of Aβ are able to induce distinct patterns of Aβ-amyloidosis when injected into mice. Overall these data suggest that the assembly of mixtures of Aβ peptides into different Aβ seeds leads to the formation of distinct subtypes of amyloid having distinctive physicochemical and biological properties which result in the generation of distinct AD molecular subgroups.

  8. Ethics Analysis of Neuroimaging in Alzheimer’s Disease

    Science.gov (United States)

    Illes, J.; Rosen, A.; Greicius, M.; Racine, E.

    2009-01-01

    This article focuses on the prospects and ethics of using neuroimaging to predict Alzheimer’s disease (AD). It is motivated by consideration of the historical roles of science in medicine and society, and considerations specifically contemporary of capabilities in imaging and aging, and the benefits and hope they bring. A general consensus is that combinations of imaging methods will ultimately be most fruitful in predicting disease. Their roll-out into translational practice will not be free of complexity, however, as culture and values differ in terms of what defines benefit and risk, who will benefit and who is at risk, what methods must be in place to assure the maximum safety, comfort, and protection of subjects and patients, and educational and policy needs. Proactive planning for the ethical and societal implications of predicting diseases of the aging brain is critical and will benefit all stakeholders— researchers, patients and families, health care providers, and policy makers. PMID:17413029

  9. [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.

  10. Alzheimer's disease and the fornix.

    Science.gov (United States)

    Oishi, Kenichi; Lyketsos, Constantine G

    2014-01-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. Researchers have long been focused on the cortical pathology of AD, since the most important pathologic features are the senile plaques found in the cortex, and the neurofibrillary tangles and neuronal loss that begin in the entorhinal cortex and the hippocampus. In addition to these gray matter (GM) structures, histopathological studies indicate that the white matter (WM) is also a good target for both the early diagnosis of AD and for monitoring disease progression. The fornix is a WM bundle that constitutes a core element of the limbic circuits, and is one of the most important anatomical structures related to memory. Functional and anatomical features of the fornix have naturally captured researchers' attention as possible diagnostic and prognostic markers of AD. Indeed, neurodegeneration of the fornix has been histologically observed in AD, and growing evidence indicates that the alterations seen in the fornix are potentially a good marker to predict future conversion from mild cognitive impairment (MCI) to AD, and even from cognitively normal individuals to AD. The degree of alteration is correlated with the degree of memory impairment, indicating the potential for the use of the fornix as a functional marker. Moreover, there have been attempts to stimulate the fornix using deep brain stimulation (DBS) to augment cognitive function in AD, and ongoing research has suggested positive effects of DBS on brain glucose metabolism in AD patients. On the other hand, disease specificity for fornix degeneration, methodologies to evaluate fornix degeneration, and the clinical significance of the fornix DBS, especially for the long-term impact on the quality of life, are mostly unknown and need to be elucidated.

  11. Alzheimer's disease: An alternative approach

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2017-01-01

    Full Text Available Alzheimer's disease (AD is the most common neurodegenerative cortical dementia. It starts with memory loss, spatial disorientation in people above the age of 65 yr with a preference to females. Its incidence is expected to increase threefold by 2050. It affects almost one out of ten persons above the age of 65 years. Majority of patients are sporadic, but a very small percentage is autosomal dominant. The pathomechanisms postulated include amyloid cascade hypothesis according to which mutation in amyloid precursor protein causes Aβ aggregation. The next hypothesis is signal transducer and activation of transcription 3 (STAT3 causing aberration in intracellular signalling pathways. Senile plaques and neurofibrillary tangles are other important pathological changes reported. It is observed that dementia research has not yielded the expected result world over, and therefore, the pitfalls with reference to known facts about diagnosis, clinical features, pathogenic mechanisms, assessment of progression, biomarkers, treatment and prevention, as well as brief information on our experiments with relatively inexpensive methods of differentiating the most common types of dementia AD and frontotemporal dementia are discussed.

  12. REVIEW: Curcumin and Alzheimer's disease.

    Science.gov (United States)

    Hamaguchi, Tsuyoshi; Ono, Kenjiro; Yamada, Masahito

    2010-10-01

    Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-β-protein (Aβ) aggregation, and Aβ-induced inflammation, as well as the activities of β-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD. © 2010 Blackwell Publishing Ltd.

  13. Neuroimaging abnormalities in Griscelli's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sarper, Nazan [Caferaga mah, Dr. Sakir Pasa sok, 7/4 Huzur Apt., 81300 Kadikoey-Istanbul (Turkey); Department of Paediatrics, Kocaeli University Faculty of Medicine, Kocaeli (Turkey); Akansel, Guer [Department of Radiodiagnosis, Kocaeli University Faculty of Medicine, Kocaeli (Turkey); Aydogan, Metin; Gedikbasi, Demet; Babaoglu, Kadir; Goekalp, Ayse Sevim [Department of Paediatrics, Kocaeli University Faculty of Medicine, Kocaeli (Turkey)

    2002-12-01

    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.)

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... Almost two-thirds of Americans with Alzheimer's are women. African-Americans are about twice as likely to ... 1 billion. Approximately two-thirds of caregivers are women, and 34 percent are age 65 or older. ...

  15. Alzheimer's Disease Facts and Figures

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    Full Text Available alz.org | Find Your Chapter 24/7 Helpline: 1.800.272.3900 Find your chapter: search by state In My Area | Alzheimer's & Dementia | Life with ALZ | Research | Professionals |

  • Alzheimer's Disease Facts and Figures

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    Full Text Available alz.org | Find Your Chapter 24/7 Helpline: 1.800.272.3900 Find your chapter: search by state In My Area | Alzheimer's & Dementia | Life with ALZ | Research | Professionals |

  • Alzheimer's Disease Facts and Figures

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    Full Text Available ... third parties. Please read our security and privacy policy . Plan ahead Get help and support I have ... Us | News | Events | Press | About this Site | Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters Alzheimer's Association ...

  • Alzheimer's Disease Facts and Figures

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    Full Text Available ... with third parties. Please read our security and privacy policy . Plan ahead Get help and support I ... About Us | News | Events | Press | About this Site | Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters Alzheimer's ...

  • Alzheimer's Disease Facts and Figures

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    Full Text Available ... either through out-of-pocket health and long-term care expenses or from the value of unpaid ... spending. The costs of health care and long-term care for individuals with Alzheimer's or other dementias ...

  • Alzheimer's Disease Facts and Figures

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    Full Text Available ... high. Invest in a world without Alzheimer's. Donate Caregivers Eighty-three percent of the help provided to ... comes from family members, friends or other unpaid caregivers. Nearly half of all caregivers who provide help ...

    1. Alzheimer's Disease Facts and Figures

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      Full Text Available ... Read past editions . Sign up for our e-newsletter Stay up-to-date on the latest news ... First name: Last name: *Email: *Zip: Weekly E-Newsletter Breaking Research Updates The Alzheimer's Association does not ...

    2. Alzheimer's Disease Facts and Figures

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      Full Text Available ... three percent of the help provided to older adults in the United States comes from family members, ... of all caregivers who provide help to older adults do so for someone with Alzheimer's or another ...

    3. Alzheimer's Disease Facts and Figures

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      Full Text Available ... is having in your state. Read past editions . Sign up for our e-newsletter Stay up-to- ... researcher Message boards Get the facts 10 warning signs & symptoms What is dementia What is Alzheimer's 7 ...

    4. Alzheimer's Disease Facts and Figures

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      Full Text Available ... caregivers of those with dementia indicate substantial emotional, financial and physical difficulties. Caring for someone with Alzheimer's? ... of all elderly people who receive adult day services and nursing home care. Total per-person health ...

    5. Alzheimer's Disease Facts and Figures

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      Full Text Available ... of people age 65 and older in the United States, particularly the oldest-old, the number of new ... is projected to soar. Today, someone in the United States develops Alzheimer's dementia every 66 seconds. By mid- ...

    6. Alzheimer's Disease Facts and Figures

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      Full Text Available ... search by state In My Area | Alzheimer's & Dementia | Life with ALZ | Research | Professionals | We Can Help | Join ... individuals to prepare legal, financial and end-of-life plans while they are still cognitively able to ...

    7. Alzheimer's Disease Facts and Figures

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      Full Text Available ... diagnosis earlier than at any other time in history. In addition to providing significant medical, emotional and ... the U.S. government and diagnosed individuals. Among all Americans alive today, if those who will get Alzheimer's ...

    8. Alzheimer's Disease Facts and Figures

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      Full Text Available ... whites. Hispanics are about one and one-half times as likely to have Alzheimer's or other dementias ... an accurate diagnosis earlier than at any other time in history. In addition to providing significant medical, ...

    9. Alzheimer's Disease Facts and Figures

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      Full Text Available ... Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable ... boards Get the facts 10 warning signs & symptoms What is dementia What is Alzheimer's 7 stages of ...

    10. Alzheimer's Disease Facts and Figures

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      Full Text Available ... caregivers are "sandwich generation" caregivers — meaning that they care not only for an aging parent, but also ... Resources Cost to Nation The costs of health care and long-term care for individuals with Alzheimer's ...

    11. Cognitive reserve in ageing and Alzheimer's disease

      OpenAIRE

      Stern, Yaakov

      2012-01-01

      The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's diseas...

    12. Alzheimer's disease due to loss of function

      DEFF Research Database (Denmark)

      Kepp, Kasper Planeta

      2016-01-01

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

    13. [Anti-ageing therapies in Alzheimer's disease].

      Science.gov (United States)

      Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael

      Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

    14. [Anesthesia and Alzheimer disease - Current perceptions].

      Science.gov (United States)

      Marques, Ana Filipa Vieira da Silva Ferreira; Lapa, Teresa Alexandra Santos Carvalho

      It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre-clinical and clinical data related to anesthesia and this disease. Alzheimer disease affects about 5% of the population over 65 years old, with age being the main risk factor and being associated with a high morbidity. Current evidence questions a possible association between anesthesia, surgery, and long-term cognitive effects, including Alzheimer disease. Although data from some animal studies suggest an association between anesthesia and neurotoxicity, this link remains inconclusive in humans. We performed a review of the literature in which we selected scientific articles in the PubMed database, published between 2005 and 2016 (one article from 1998 due to its historical relevance), in English, which address the possible relationship between anesthesia and Alzheimer disease. 49 articles were selected. The possible relationship between anesthetic agents, cognitive dysfunction, and Alzheimer disease remains to be clarified. Prospective cohort studies or randomized clinical trials for a better understanding of this association will be required. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

    15. Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome

      Science.gov (United States)

      Hamlett, Eric D.; Boger, Heather A.; Ledreux, Aurélie; Kelley, Christy M.; Mufson, Elliott J.; Falangola, Maria F.; Guilfoyle, David N.; Nixon, Ralph A.; Patterson, David; Duval, Nathan; Granholm, Ann-Charlotte E.

      2016-01-01

      Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expectancy due to progress in treatment of medical comorbidities, which has allowed this population to reach the age when they develop early onset Alzheimer’s disease (AD). Individuals with DS develop cognitive and pathological hallmarks of AD in their fourth or fifth decade, and are currently lacking successful prevention or treatment options for dementia. The profound memory deficits associated with DS-related AD (DS-AD) have been associated with degeneration of several neuronal populations, but mechanisms of neurodegeneration are largely unexplored. The most successful animal model for DS is the Ts65Dn mouse, but several new models have also been developed. In the current review, we discuss recent findings and potential treatment options for the management of memory loss and AD neuropathology in DS mouse models. We also review age-related neuropathology, and recent findings from neuroimaging studies. The validation of appropriate DS mouse models that mimic neurodegeneration and memory loss in humans with DS can be valuable in the study of novel preventative and treatment interventions, and may be helpful in pinpointing gene-gene interactions as well as specific gene segments involved in neurodegeneration. PMID:26391050

    16. 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.

    17. Denial of memory deficit in Alzheimer's disease.

      Science.gov (United States)

      Sevush, S; Leve, N

      1993-05-01

      Patients with probable Alzheimer's disease often deny or underestimate the severity of their memory impairment. The authors examined the relationships between denial and severity of cognitive impairment and between denial and the presence of depressed mood and sad affect in 128 patients with probable Alzheimer's disease. Denial of memory deficit was evaluated by structured interview. Cognition was evaluated with a quantitative examination that assessed performance on 16 subtests. Depression was rated by using a scale that included patients' self-ratings as well as caregivers' and examiners' assessments of the patient's mood and affect. Pearson correlation coefficients were used to quantify the relationship between denial and demographic, cognitive, and depression variables. Stepwise multiple regression analysis was used to further examine the relationship between denial and individual cognitive subset scores. Denial did not correlate with age at onset of Alzheimer's disease, duration of illness, or educational background. It did correlate with gender: women exhibited greater denial than men. A significant correlation was found between denial and overall severity of cognitive deficit and particularly with impairment in object naming. A negative correlation was found between denial and depression. The association between denial and cognitive impairment may suggest that denial of probable Alzheimer's disease results from disruption of cognitive abilities needed for awareness of illness. The negative association between denial and depression may suggest that depression in Alzheimer's disease is in part reactive in nature.

    18. Myoclonic epilepsy in Down syndrome and Alzheimer disease.

      Science.gov (United States)

      Aller-Alvarez, J S; Menéndez-González, M; Ribacoba-Montero, R; Salvado, M; Vega, V; Suárez-Moro, R; Sueiras, M; Toledo, M; Salas-Puig, J; Álvarez-Sabin, J

      2017-03-01

      Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

    19. [Possibilities of modern imaging technologies in early diagnosis of Alzheimer disease].

      Science.gov (United States)

      Unschuld, Paul G

      2015-04-01

      Recent advances in neuroimaging technology and image analysis algorithms have significantly contributed to a better understanding of spatial and temporal aspects of brain change associated with Alzheimer Disease. The current review will demonstrate how functional (fMRI) and structural magnetic resonance imaging (MRI) techniques may be used to identify distinct patterns of brain change associated with disease progression and also increased risk for Alzheimer Disease. Moreover, Positron Emission Tomography (PET) based measures of glucosemetabolism (Fluorodeoxyglucose, FDG) and Amyloid-beta plaque density (11-C-Pittsburgh Compound B, PiB and 18-F) will be reviewed regarding their diagnostic value for assessing the individual degree of Alzheimer -pathology and thus complement the information provided by MRI and other clinical measures.

    20. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

      Science.gov (United States)

      2013-11-05

      ... National Alzheimer's Disease Awareness Month, 2013 By the President of the United States of America A Proclamation Alzheimer's disease is an irreversible and progressive brain disease that slowly erodes precious..., including senior citizens as well as younger Americans with early-onset Alzheimer's disease. This month, we...

    1. Llama VHH as immunotherapeutics in Alzheimer's disease

      NARCIS (Netherlands)

      Dorresteijn, B.

      2013-01-01

      Alzheimer's Disease (AD) is the most common form of dementia among elderly in the Western world. AD is a devastating neurodegenerative disease where patients starting with episodic memory problems end up completely bedridden and care dependent. At present there is no real therapy stopping or

    2. Neuroinflammation in Alzheimer's disease wanes with age

      NARCIS (Netherlands)

      Hoozemans, Jeroen J. M.; Rozemuller, Annemieke J. M.; van Haastert, Elise S.; Eikelenboom, Piet; van Gool, Willem A.

      2011-01-01

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

    3. Neuroinflammation in Alzheimer's disease wanes with age

      NARCIS (Netherlands)

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

      2011-01-01

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

    4. Alzheimer's disease therapies: Selected advances and future ...

      African Journals Online (AJOL)

      Among the neurodegenerative diseases, Alzheimer's disease (AD) represents one of the biggest challenges that the modern health care system has to deal with. The lack of data about the etiology and the complexity of the underlying pathogenesis constitute the biggest struggle facing the development of new therapeutical ...

    5. 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

    6. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available alz.org | Find Your Chapter 24/7 Helpline: 1.800.272.3900 Find your chapter: search by ... under age 65 and have younger-onset Alzheimer's. One in 10 people age 65 and older (10 ...

    7. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... one-quarter of dementia caregivers are "sandwich generation" caregivers — meaning that they care not only for an aging parent, but also ... and support I have Alzheimer's I am a caregiver I am a care professional I am a physician I am a ...

    8. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... Almost two-thirds of Americans with Alzheimer's are women. Older African-Americans are about twice as likely ... or older. Approximately two-thirds of caregivers are women; more specifically, over one-third of dementia caregivers ...

    9. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... with Alzheimer's or other dementias make up a large proportion of all elderly people who receive adult day services and nursing home care. Take action. Become an advocate SPECIAL REPORT: FINANCIAL AND PERSONAL BENEFITS OF EARLY DIAGNOSIS Early diagnosis of cognitive impairment ...

    10. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... difficulties. Caring for someone with Alzheimer's? Get Resources Cost to Nation The costs of health care and long-term care for ... is expected to be $56 billion. Health care costs increase with the presence of dementia. People with ...

    11. Current treatments for patients with Alzheimer disease.

      Science.gov (United States)

      Osborn, Gerald G; Saunders, Amanda Vaughn

      2010-09-01

      There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.

    12. A computed tomography study of Alzheimer's disease

      International Nuclear Information System (INIS)

      Arai, H.; Kobayashi, K.; Juntendo Univ. School of Medicine, Tokyo; Ikeda, Y.; Nagao, Y.; Ogihara, R.; Kosaka, K.; Psychiatric Research Inst. of Tokyo

      1983-01-01

      Computed tomography (CT) was used to study cerebral atrophy in 18 patients with clinically diagnosed Alzheimer's disease of presenile type and in 14 healthy age-matched subjects as controls. Using the computerized planimetric method, Subarachnoid Space Volume Index and Ventricle Volume Index were calculated as the measure of cortical atrophy and ventricular dilatation respectively. From the results the following conclusions were drawn: 1. The cerebral atrophy in Alzheimer patients could be attributable to the disease processes rather than to physiological aging of the brain. 2. The degree of atrophy increases in parallel with the progress of the clinical stage, and the cortical atrophy is already apparent at an early stage, whereas the ventricular dilatation becomes pronounced at later stages. 3. CT could be one of the most useful clinical tests available for the diagnosis of Alzheimer's disease. (orig.) [de

    13. 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 (John); 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.

    14. Machine learning for the assessment of Alzheimer's disease through DTI

      Science.gov (United States)

      Lella, Eufemia; Amoroso, Nicola; Bellotti, Roberto; Diacono, Domenico; La Rocca, Marianna; Maggipinto, Tommaso; Monaco, Alfonso; Tangaro, Sabina

      2017-09-01

      Digital imaging techniques have found several medical applications in the development of computer aided detection systems, especially in neuroimaging. Recent advances in Diffusion Tensor Imaging (DTI) aim to discover biological markers for the early diagnosis of Alzheimer's disease (AD), one of the most widespread neurodegenerative disorders. We explore here how different supervised classification models provide a robust support to the diagnosis of AD patients. We use DTI measures, assessing the structural integrity of white matter (WM) fiber tracts, to reveal patterns of disrupted brain connectivity. In particular, we provide a voxel-wise measure of fractional anisotropy (FA) and mean diffusivity (MD), thus identifying the regions of the brain mostly affected by neurodegeneration, and then computing intensity features to feed supervised classification algorithms. In particular, we evaluate the accuracy of discrimination of AD patients from healthy controls (HC) with a dataset of 80 subjects (40 HC, 40 AD), from the Alzheimer's Disease Neurodegenerative Initiative (ADNI). In this study, we compare three state-of-the-art classification models: Random Forests, Naive Bayes and Support Vector Machines (SVMs). We use a repeated five-fold cross validation framework with nested feature selection to perform a fair comparison between these algorithms and evaluate the information content they provide. Results show that AD patterns are well localized within the brain, thus DTI features can support the AD diagnosis.

    15. [Prevention and treatment of Alzheimer disease].

      Science.gov (United States)

      Donoso S, Archibaldo; Delgado D, Carolina

      2009-02-01

      The pharmacological interventions for Alzheimer disease should be based in its pathogenic mechanisms such as amyloidogenesis, tau hyperphosphorilation, disturbances in neurotransmission and changes in neuronal trophism. Other therapies derive from epidemiological observations, such as antioxidants and anti-inflammatory drugs, estrogens, statins and anti hypertensive drugs. Some life style interventions, such as changes in diet, exercise and brain stimulation could also be beneficial for the prevention of Alzheimer disease. Ongoing research on pathogenic mechanisms promises the discovery of more effective therapies. Healthy life style should always be recommended due to its benefit and lack of untoward effects.

    16. White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

      Science.gov (United States)

      Provenzano, Frank A; Muraskin, Jordan; Tosto, Giuseppe; Narkhede, Atul; Wasserman, Ben T; Griffith, Erica Y; Guzman, Vanessa A; Meier, Irene B; Zimmerman, Molly E; Brickman, Adam M

      2013-04-01

      Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). The Alzheimer's Disease Neuroimaging Initiative public database. The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. Clinical AD diagnosis and WMH volume. Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. White matter hyperintensities contribute to the presentation of AD and, in the context of

    17. Lexical priming in Alzheimer's disease and aphasia.

      Science.gov (United States)

      Arroyo-Anlló, Eva Maria; Beauchamps, Mireille; Ingrand, Pierre; Neau, Jean Philippe; Gil, Roger

      2013-01-01

      Lexical priming was examined in patients with Alzheimer's disease and in aphasic patients. Control participants were divided into young and elderly [cf. Arroyo-Anlló et al.: Eur J Cogn Psychol 2004;16:535-553]. For lexical priming, a word-stem completion task was used. Normal elderly participants had lexical priming scores that were significantly lower than those of young individuals. Analysis of covariance with age and educational level as covariates showed that the control participants, aphasic and Alzheimer patients did not differ significantly on the lexical priming task. Our results suggest that performance in the lexical priming task diminishes with physiological aging, but is not significantly affected by mild or moderate Alzheimer's disease or by fluent or non-fluent aphasia. Copyright © 2013 S. Karger AG, Basel.

    18. Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non-Alzheimer Disease Pathophysiology.

      Science.gov (United States)

      Schreiber, Stefanie; Schreiber, Frank; Lockhart, Samuel N; Horng, Andy; Bejanin, Alexandre; Landau, Susan M; Jagust, William J

      2017-06-01

      There are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)-negative (Aβ-) suspected non-Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts. To examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts. A longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30.5 months from August 1, 2005, to June 30, 2015. Several neurodegeneration biomarkers and longitudinal cognitive function were compared between patients with distinct SNAP (Aβ- and neurodegeneration-positive [Aβ-N+]) subtypes and their Aβ+N+ counterparts. Participants were classified according to the results of their florbetapir F-18 (Aβ) positron emission tomography and their Alzheimer disease-associated neurodegeneration status (temporoparietal glucose metabolism determined by fluorodeoxyglucose F 18 [FDG]-labeled positron emission tomography and/or hippocampal volume [HV] determined by magnetic resonance imaging: participants with subthreshold HV values were regarded as exhibiting hippocampal volume atrophy [HV+], while subthreshold mean FDG values were considered as FDG hypometabolism [FDG+]). The study comprised 265 cognitively normal individuals (135 women and 130 men; mean [SD] age, 75.5 [6.7] years) and 522 patients with MCI (225 women and 297 men; mean [SD] age, 72.6 [7.8] years). A total of 469 individuals with MCI had data on neurodegeneration biomarkers; of these patients, 107 were Aβ-N+ (22.8%; 63 FDG+, 82 HV+, and 38 FDG+HV+) and 187 were Aβ+N+ (39.9%; 135 FDG+, 147 HV+, and 95 FDG+HV+ cases). A total of 209 cognitively normal participants had data on neurodegeneration biomarkers; of these, 52 were

    19. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010

      Science.gov (United States)

      2010-11-04

      ... effective treatments and a cure, we must continue to support both Alzheimer's disease research and the... National Alzheimer's Disease Awareness Month, 2010 By the President of the United States of America A Proclamation Alzheimer's disease tragically robs individuals of their memories and leads to progressive mental...

    20. 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...

    1. 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-?, intracellular ...

    2. Aripiprazole in the treatment of Alzheimer's disease

      NARCIS (Netherlands)

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

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

    3. Cerebrospinal fluid markers of Alzheimer's disease

      NARCIS (Netherlands)

      van Gool, W. A.; Bolhuis, P. A.

      1991-01-01

      OBJECTIVE: To review studies on cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) in order to answer the question whether CSF contains a specific marker which can be used to support a clinical diagnosis of AD. DATA SOURCES: Studies identified through an English-language literature

    4. Hypocretin (orexin) loss in Alzheimer's disease.

      NARCIS (Netherlands)

      Fronczek, R.; Geest, S. de; Frolich, M.; Overeem, S.; Roelandse, F.W.; Lammers, G.J.; Swaab, D.F.

      2012-01-01

      Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter

    5. Hypocretin (orexin) loss in Alzheimer's disease

      NARCIS (Netherlands)

      Fronczek, Rolf; van Geest, Sarita; Frölich, Marijke; Overeem, Sebastiaan; Roelandse, Freek W. C.; Lammers, Gert Jan; Swaab, Dick F.

      2012-01-01

      Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter

    6. Early psychosocial intervention in Alzheimer's disease

      DEFF Research Database (Denmark)

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

      2014-01-01

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

    7. Retrograde amnesia in patients with Alzheimer's disease

      NARCIS (Netherlands)

      Meeter, M.; Eijsackers, E; Mulder, J

      2006-01-01

      Patients with mild to moderate Alzheimer's disease and normal controls were tested on two retrograde memory tests, one based on public events, and the other querying autobiographical memory. On both tests, patients showed strong decrements as compared to normal controls, pointing to retrograde

    8. 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...

    9. 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...

    10. 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

    11. Diagnosis and treatment of Alzheimer's disease

      International Nuclear Information System (INIS)

      Hampel, H.; Padberg, F.; Koetter, H.U.; Teipel, S.J.; Ehrhardt, T.; Hegerl, U.; Stuebner, S.; Moeller, H.J.

      1997-01-01

      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) [de

    12. Pharmacological treatment of Alzheimer's disease

      OpenAIRE

      Forlenza, Orestes V.

      2005-01-01

      O presente artigo de revisão aborda as perspectivas atuais e futuras no tratamento farmacológico da doença de Alzheimer. Os benefícios e limitações da terapia de reposição colinérgica, representada fundamentalmente pelos inibidores das colinesterases, são apresentados com base em dados de pesquisas neurobiológicas, farmacológicas e clínicas, ilustrados pelos principais estudos controlados por placebo e por estudos recentes de metanálise. O papel da memantina nos casos de demência moderada a g...

    13. Unbiased tensor-based morphometry: improved robustness and sample size estimates for Alzheimer's disease clinical trials.

      Science.gov (United States)

      Hua, Xue; Hibar, Derrek P; Ching, Christopher R K; Boyle, Christina P; Rajagopalan, Priya; Gutman, Boris A; Leow, Alex D; Toga, Arthur W; Jack, Clifford R; Harvey, Danielle; Weiner, Michael W; Thompson, Paul M

      2013-02-01

      Various neuroimaging measures are being evaluated for tracking Alzheimer's disease (AD) progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated. Here we analyzed the full MRI dataset from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) and assessed several sources of bias that can arise when tracking brain changes with structural brain imaging methods, as part of a pipeline for tensor-based morphometry (TBM). In all healthy subjects who completed MRI scanning at screening, 6, 12, and 24months, brain atrophy was essentially linear with no detectable bias in longitudinal measures. In power analyses for clinical trials based on these change measures, only 39AD patients and 95 mild cognitive impairment (MCI) subjects were needed for a 24-month trial to detect a 25% reduction in the average rate of change using a two-sided test (α=0.05, power=80%). Further sample size reductions were achieved by stratifying the data into Apolipoprotein E (ApoE) ε4 carriers versus non-carriers. We show how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI. Copyright © 2012 Elsevier Inc. All rights reserved.

    14. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

      Science.gov (United States)

      2012-02-24

      ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Draft National Plan To Address Alzheimer's Disease AGENCY... Alzheimer's Disease, which is available at http://aspe.hhs.gov/daltcp/napa/NatlPlan.shtml . DATES: Submit... . Background On January 4, 2011, President Barack Obama signed into law the National Alzheimer's Project Act...

    15. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... same category as other chronic diseases, such as cardiovascular disease or diabetes, which can be ... Disease Facts and Figures report contains data on the impact of this disease ...

    16. Application of PET in Alzheimer's disease

      International Nuclear Information System (INIS)

      Zhang Chun

      2003-01-01

      Alzheimer's disease (AD) is a neurodegenerative disease of central nervous system that causes progressive cognitive and memory deterioration in the elderly people. Affected brains of AD patients are characterized by the presence of senile plaques (SP) and neurofilbrillary tangles (NFT). The review will focus on the application of positron emission tomography (PET) in the diagnosis, progression prediction, treatment and evaluation of neurotransmission activity of AD

    17. A Critical Assessment of Research on Neurotransmitters in Alzheimer's Disease.

      Science.gov (United States)

      Reddy, P Hemachandra

      2017-01-01

      The purpose of this mini-forum, "Neurotransmitters and Alzheimer's Disease", is to critically assess the current status of neurotransmitters in Alzheimer's disease. Neurotransmitters are essential neurochemicals that maintain synaptic and cognitive functions in mammals, including humans, by sending signals across pre- to post-synaptic neurons. Authorities in the fields of synapses and neurotransmitters of Alzheimer's disease summarize the current status of basic biology of synapses and neurotransmitters, and also update the current status of clinical trials of neurotransmitters in Alzheimer's disease. This article discusses the prevalence, economic impact, and stages of Alzheimer's dementia in humans.

    18. 3D scattering transforms for disease classification in neuroimaging

      Directory of Open Access Journals (Sweden)

      Tameem Adel

      2017-01-01

      Full Text Available Classifying neurodegenerative brain diseases in MRI aims at correctly assigning discrete labels to MRI scans. Such labels usually refer to a diagnostic decision a learner infers based on what it has learned from a training sample of MRI scans. Classification from MRI voxels separately typically does not provide independent evidence towards or against a class; the information relevant for classification is only present in the form of complicated multivariate patterns (or “features”. Deep learning solves this problem by learning a sequence of non-linear transformations that result in feature representations that are better suited to classification. Such learned features have been shown to drastically outperform hand-engineered features in computer vision and audio analysis domains. However, applying the deep learning approach to the task of MRI classification is extremely challenging, because it requires a very large amount of data which is currently not available. We propose to instead use a three dimensional scattering transform, which resembles a deep convolutional neural network but has no learnable parameters. Furthermore, the scattering transform linearizes diffeomorphisms (due to e.g. residual anatomical variability in MRI scans, making the different disease states more easily separable using a linear classifier. In experiments on brain morphometry in Alzheimer's disease, and on white matter microstructural damage in HIV, scattering representations are shown to be highly effective for the task of disease classification. For instance, in semi-supervised learning of progressive versus stable MCI, we reach an accuracy of 82.7%. We also present a visualization method to highlight areas that provide evidence for or against a certain class, both on an individual and group level.

    19. Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease

      OpenAIRE

      Hai-Chen Pi; Yu-Feng Xu; Rong Xu; Zhi-Kai Yang; Zhen Qu; Yu-Qing Chen; Gui-Ling Liu; Jie Dong

      2016-01-01

      Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, educa...

    20. Accelerating stem cell trials for Alzheimer's disease.

      Science.gov (United States)

      Hunsberger, Joshua G; Rao, Mahendra; Kurtzberg, Joanne; Bulte, Jeff W M; Atala, Anthony; LaFerla, Frank M; Greely, Henry T; Sawa, Akira; Gandy, Sam; Schneider, Lon S; Doraiswamy, P Murali

      2016-02-01

      At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and offer only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

    1. 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 amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease. Here, a new loss-of-function hypothesis is synthesized that accounts...

    2. Anti-amyloid treatments in Alzheimer's disease.

      Science.gov (United States)

      Sapra, Mamta; Kim, Kye Y

      2009-06-01

      Alzheimer's disease is one of the most challenging threats to the healthcare system in society. One of the main characteristic of Alzheimer's disease (AD) pathology is formation of amyloid plaques from accumulation of amyloid beta peptide. The therapeutic agents that are currently available for AD including acetylcholinesterase inhibitors (AchEIs) and the N-methyl-D-aspartate (NMDA) antagonist are focused on improving the symptoms and do not revert the progression of the disease. This limitation coupled with the burgeoning increase in the prevalence of AD and resultant impact on healthcare economics calls for more substantial treatments for AD. According to the leading amyloid hypothesis, cleavage of amyloid precursor protein to release amyloid beta peptide is the critical event in pathogenesis of Alzheimer's disease. Recently treatment strategies have been focused on modifying the formation, clearance and accumulation of neurotoxic amyloid beta peptide. This article reviews different therapeutic approaches that have been investigated to target amyloid beta ranging from secretase modulators, antiaggregation agents to amyloid immunotherapy. Authors review the different novel drugs which are in clinical trials.

    3. Alzheimer's Disease Facts and Figures

      Medline Plus

      Full Text Available ... 15.9 million family and friends provided 18.2 billion hours of unpaid assistance to those with ... other chronic diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and ...

    4. Alzheimer's Disease at a Glance

      Science.gov (United States)

      ... R S T U V W X Y Z Alzheimer’s Disease at a Glance Researchers have explored many ... health approaches for preventing or slowing dementia, including Alzheimer’s disease. Currently, there is no strong evidence that ...

    5. Does prevention for Alzheimer's disease exist?

      Directory of Open Access Journals (Sweden)

      Sonia Maria Dozzi Brucki

      Full Text Available Abstract The prevention of Alzheimer's disease is a growing public health concern amidst an ageing population. Meanwhile, there is no effective or curative treatment available where prevention could greatly reduce health costs. This review was based on reports of potential preventive factors, including modifiable lifestyle factors, as well as preventive pharmacological strategies. Although the present review was not systematic, the reports selected from PubMed using "Alzheimer's disease" and "prevention" as key-words, allow us to affirm that pursuing a healthy lifestyle; physical, cognitive, leisure activities; good social engagement; a high consumption of fish, low consumption of dietary fat and moderate consumption of wine, and control of vascular risk factors appear to be potential factors for delaying dementia.

    6. Cognitive reserve in ageing and Alzheimer's disease

      Science.gov (United States)

      Stern, Yaakov

      2012-01-01

      The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's disease in individuals with higher educational or occupational attainment. It is convenient to think of two types of reserve: brain reserve, which refers to actual differences in the brain itself that may increase tolerance of pathology, and cognitive reserve. Cognitive reserve refers to individual differences in how tasks are performed that may allow some people to be more resilient than others. The concept of cognitive reserve holds out the promise of interventions that could slow cognitive aging or reduce the risk of dementia. PMID:23079557

    7. 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.

    8. ABO and Rhesus blood groups in Alzheimer's disease.

      Science.gov (United States)

      Renvoize, E B

      1985-01-01

      ABO and rhesus (Rh) blood groups were examined in 124 patients with presenile dementia of the Alzheimer type (PDAT) and senile dementia of the Alzheimer type (SDAT), and their distribution was compared with controls. No significant associations between these blood groups and Alzheimer's disease (AD) were found after statistical correction for multiple comparisons.

    9. 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

    10. [Levels of burden of Alzheimer disease caregivers].

      Science.gov (United States)

      Passoni, Serena; Mazzà, Manuela; Zanardi, Gabriele; Bottini, Gabriella

      2010-01-01

      Our aim was to investigate the caregiver burden by means of scales to quantify the perceived burden, and the anxiety and depression levels. Seventy-seven caregivers of patients with Alzheimer disease or other kinds of dementia (19 males and 58 females) admitted to the Alzheimer Evaluation Unit of Milan Niguarda Ca'Granda Hospital, were enrolled and filled in Caregiver Burden Inventory (CBI) and the short form of the Anxiety and Depression scale (AD-R). The statistical analysis demonstrates that caregiver with relatives affected by more severe cognitive impairment (patients) show significant levels of burden and anxiety. The most relevant burden dimensions are: Time-Dependence Burden, Developmental Burden and Physical Burden. Time-Dependence Burden and Social Burden significantly correlate with cognitive (p = 0.01, p = 0.05) and functional rates of patients (p = 0.01, p = 0.05), whereas Developmental Burden only correlates with cognitive rates (p = 0.01). The more prolonged patients' disease the higher the caregivers'anxiety level (p caregivers' sample, and the cognitive and functional state of patients. Alzheimer disease caregivers need an increase of their personal time anda specific intervention aimed to reduce the perceived feeling of social isolation, the physical distress and the anxious and depressive symptoms.

    11. Alzheimer's disease: a report from the 7th Kuopio Alzheimer symposium.

      Science.gov (United States)

      Haapasalo, Annakaisa; Pikkarainen, Maria; Soininen, Hilkka

      2015-10-01

      The 7th Kuopio Alzheimer symposium was held on 11-13 June, 2015, in Kuopio, Finland and attracted ~250 attendees from 14 different countries around the world. The theme for the symposium in its seventh year was 'From mechanisms to prevention and intervention of Alzheimer's disease'. The 3-day international scientific symposium composed of seven oral sessions and a poster session. The program, spanning from molecular mechanisms to prevention, prediction, diagnosis and treatment of Alzheimer's disease, provided a forum for the attendees to share their research, network and to obtain a comprehensive overview of the current status and future directions of research into Alzheimer's disease.

    12. Early- and late-onset Alzheimer disease: Are they the same entity?

      Science.gov (United States)

      Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

      2018-05-01

      Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

    13. Blood-based protein biomarkers for diagnosis of Alzheimer disease.

      Science.gov (United States)

      Doecke, James D; Laws, Simon M; Faux, Noel G; Wilson, William; Burnham, Samantha C; Lam, Chiou-Peng; Mondal, Alinda; Bedo, Justin; Bush, Ashley I; Brown, Belinda; De Ruyck, Karl; Ellis, Kathryn A; Fowler, Christopher; Gupta, Veer B; Head, Richard; Macaulay, S Lance; Pertile, Kelly; Rowe, Christopher C; Rembach, Alan; Rodrigues, Mark; Rumble, Rebecca; Szoeke, Cassandra; Taddei, Kevin; Taddei, Tania; Trounson, Brett; Ames, David; Masters, Colin L; Martins, Ralph N

      2012-10-01

      To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. General community-based, prospective, longitudinal study of aging. A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.

    14. 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....

    15. Locally linear embedding (LLE) for MRI based Alzheimer's disease classification.

      Science.gov (United States)

      Liu, Xin; Tosun, Duygu; Weiner, Michael W; Schuff, Norbert

      2013-12-01

      Modern machine learning algorithms are increasingly being used in neuroimaging studies, such as the prediction of Alzheimer's disease (AD) from structural MRI. However, finding a good representation for multivariate brain MRI features in which their essential structure is revealed and easily extractable has been difficult. We report a successful application of a machine learning framework that significantly improved the use of brain MRI for predictions. Specifically, we used the unsupervised learning algorithm of local linear embedding (LLE) to transform multivariate MRI data of regional brain volume and cortical thickness to a locally linear space with fewer dimensions, while also utilizing the global nonlinear data structure. The embedded brain features were then used to train a classifier for predicting future conversion to AD based on a baseline MRI. We tested the approach on 413 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had baseline MRI scans and complete clinical follow-ups over 3 years with the following diagnoses: cognitive normal (CN; n=137), stable mild cognitive impairment (s-MCI; n=93), MCI converters to AD (c-MCI, n=97), and AD (n=86). We found that classifications using embedded MRI features generally outperformed (pclassifications using the original features directly. Moreover, the improvement from LLE was not limited to a particular classifier but worked equally well for regularized logistic regressions, support vector machines, and linear discriminant analysis. Most strikingly, using LLE significantly improved (p=0.007) predictions of MCI subjects who converted to AD and those who remained stable (accuracy/sensitivity/specificity: =0.68/0.80/0.56). In contrast, predictions using the original features performed not better than by chance (accuracy/sensitivity/specificity: =0.56/0.65/0.46). In conclusion, LLE is a very effective tool for classification studies of AD using multivariate MRI data. The improvement in

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

      Directory of Open Access Journals (Sweden)

      Sei J Lee

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

    17. Retrograde memory in cerebrovascular disease and Alzheimer's disease.

      Science.gov (United States)

      Capruso, Daniel X; Hamsher, Kerry deS

      2012-05-01

      Retrograde memory is frequently tested in the mental status examination of patients with stroke or degenerative dementia. The goal of this experiment was to compare gradients of retrograde memory in patients without neurologic disease (n = 26), patients with cerebrovascular disease (n = 43), and patients with probable Alzheimer's disease (n = 27). Patients were asked to recall and then name photographs of the 6 most recent US presidents. The free recall of patients with both cerebrovascular disease and probable Alzheimer's disease formed an exaggeration of the normal forgetting curve seen in control patients, in that the most recent presidents were most likely to be remembered. For photo naming, control patients showed essentially no forgetting, whereas patients with cerebrovascular disease or Alzheimer's disease had substantial memory loss with no temporal gradient. Alzheimer's disease caused significantly worse retrograde memory loss than did cerebrovascular disease, despite the two groups' equivalence in global intellectual functioning. Consistent with the focal or multifocal nature of cerebrovascular disease, stepwise multiple regression of retrograde memory on neuropsychological testing indicated that producing names by free recall was predicted by aphasic deficits, and that photo naming was predicted by visuoperceptual deficits. In Alzheimer's disease, free recall was predicted primarily by deficits in verbal new learning, consistent with amnesia, whereas photo naming was predicted by loss of general knowledge, consistent with dementia. The results are consistent with the idea that free recall of names from the past is a form of episodic memory, whereas naming of famous faces from the past is a form of semantic memory. Published by Elsevier Inc.

    18. Alzheimer's Disease: Aging, Insomnia and Epigenetics

      Directory of Open Access Journals (Sweden)

      Tzong Yuan Wu

      2010-12-01

      Full Text Available Alzheimer's disease (AD is the most common form of dementia. Severe memory loss, confusion, and impaired cognitive abilities characterize AD. It was only a century after Alzheimer's discovery that scientists were able to shed light on the mystery of its cause, but AD has also become a globally important health issue and the treatment of AD is a challenge for modern medicine. At present, there are five drugs approved in the United States for the treatment of AD, namely, donepezil, galantamine, rivastigmine, and tacrine (which are all cholinesterase inhibitors; and memantine (which is a glutamate receptor antagonist. However, these drugs show only modest effects on AD patients. Thus, new investigations are necessary for pharmacological development in AD. This brief review focuses on new studies that demonstrate the link between epigenetics and AD, and explores the possibility that insomnia may be one factor that effects AD.

    19. 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.

    20. The Neuropsychological Profile of Alzheimer Disease

      Science.gov (United States)

      Weintraub, Sandra; Wicklund, Alissa H.; Salmon, David P.

      2012-01-01

      Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from “normal,” age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease. PMID:22474609

    1. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE.

      Science.gov (United States)

      Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

      2015-12-01

      The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM.

    2. Genome-wide association study of language performance in Alzheimer's disease.

      Science.gov (United States)

      Deters, Kacie D; Nho, Kwangsik; Risacher, Shannon L; Kim, Sungeun; Ramanan, Vijay K; Crane, Paul K; Apostolova, Liana G; Saykin, Andrew J

      2017-09-01

      Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (pbrain structures, as a putative gene associated with language dysfunction in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

    3. Quantifying cognition and behavior in normal aging, mild cognitive impairment, and Alzheimer's disease

      Science.gov (United States)

      Giraldo, Diana L.; Sijbers, Jan; Romero, Eduardo

      2017-11-01

      The diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) is based on neuropsychological evaluation of the patient. Different cognitive and memory functions are assessed by a battery of tests that are composed of items devised to specifically evaluate such upper functions. This work aims to identify and quantify the factors that determine the performance in neuropsychological evaluation by conducting an Exploratory Factor Analysis (EFA). For this purpose, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), EFA was applied to 67 item scores taken from the baseline neuropsychological battery of the three phases of ADNI study. The found factors are directly related to specific brain functions such as memory, behavior, orientation, or verbal fluency. The identification of factors is followed by the calculation of factor scores given by weighted linear combinations of the items scores.

    4. Neuroimaging markers for the prediction and early diagnosis of Alzheimer’s disease dementia

      Science.gov (United States)

      Ewers, Michael; Sperling, Reisa A.; Klunk, William E.; Weiner, Michael W.; Hampel, Harald

      2011-01-01

      Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease. At the time of clinical manifestation of dementia, significant irreversible brain damage is already present, rendering the diagnosis of AD at early stages of the disease an urgent prerequisite for therapeutic treatment to halt, or at least slow, disease progression. In this Review, we discuss various neuroimaging measures that are proving to have potential value as biomarkers of AD pathology for the detection and prediction of AD before the onset of dementia. Recent studies that have identified AD-like structural and functional brain changes in elderly people who are cognitively within the normal range or who have mild cognitive impairment (MCI) are discussed. A dynamic sequence model of changes that occur in neuroimaging markers during the different disease stages is presented and the predictive value of multimodal neuroimaging for AD dementia is considered. PMID:21696834

    5. Modern approach in the therapy of Alzheimer's disease

      Directory of Open Access Journals (Sweden)

      D. I. Rodin

      2014-01-01

      Full Text Available Alzheimer's disease is a well-known neurodegenerative disorder. One of its main risk factors is age. Due to a worldwide increase of human longevity Alzheimer's disease became the most common form of dementia. The disease has been studied in different countries for many decades but still its etiology remains unclear. By now there is no cure for Alzheimer's, moreover there are no that can at least slow down the disease progression. In this review we made an attempt to summarize all current studies of the most advanced drugs for Alzheimer's.

    6. Alzheimer's disease: new diagnostic and therapeutic tools

      Directory of Open Access Journals (Sweden)

      Caruso Calogero

      2008-08-01

      Full Text Available Abstract On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lectures of M. Racchi on History and future perspectives of Alzheimer Biomarkers and of G. Scapagnini on Cellular Stress Response and Brain Ageing are summarized. Alzheimer's disease (AD is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for clinica dementia. AD prevention is an important goal of ongoing research. Two objectives must be accomplished to make prevention feasible: i individuals at high risk of AD need to be identified before the earliest symptoms become evident, by which time extensive neurodegeneration has already occurred and intervention to prevent the disease is likely to be less successful and ii safe and effective interventions need to be developed that lead to a decrease in expression of this pathology. On the whole, data here reviewed strongly suggest that the measurement of conformationally altered p53 in blood cells has a high ability to discriminate AD cases from normal ageing, Parkinson's disease and other dementias. On the other hand, available data on the involvement of curcumin in restoring cellular homeostasis and rebalancing redox equilibrium, suggest that curcumin might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation, such as AD.

    7. [Clinical presentation of Moroccan cases with Alzheimer's disease].

      Science.gov (United States)

      El Kadmiri, N; Zaid, Y; Hamzi, K; Nadifi, S; Slassi, I; El Moutawakil, B

      2014-12-01

      The diagnostic approach for Alzheimer's disease is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state. In this context, this study was conducted to assess the correlation between imaging and neuropsychological testing for cases of early-onset and late-onset Alzheimer's disease. Analysis of the clinical and paraclinical aspects of Moroccan cases with Alzheimer's disease. Seventeen sporadic cases and 8 family cases were seen at the memory clinic of the Neurology Department of the University of Casablanca Ibn Rochd Hospital. A family history was obtained through a clinical interview of the patient and a yes or no self-reporting questionnaire from the guardian or other family member. The disease was considered familial if at least one additional first degree relative suffered from early-onset AD-type dementia. All patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Written consent was obtained from the patients and their guardians prior to the study. In our study of 25 individuals, the observed mean age of AD patients was 64.52 ± 9.30 and we observed a slight female predominance (56% versus 44%). In addition, we found a prevalence of AD of approximately 20%, increasing with age, in the population below 60 years of age. Approximately half of our patients (48%) had a score lower than 10 and were affected by severe insanity, while 28% were affected by moderate severe insanity and 24% were light to moderately insane. Twenty-five patients underwent neuroimaging, 18 of whom were assessed by MRI, while 7 were assessed by CT. All patients had hippocampal atrophy, which progressed to affect others brain regions. The blood tests showed no abnormalities in the 25 enrolled AD cases. Age is undoubtedly the main risk factor for AD; this is also the true for our cases where advanced age was responsible for the exponential increase of the disease

    8. Neuroinflammation and Alzheimer disease: clinical and therapeutic implications

      NARCIS (Netherlands)

      Eikelenboom, P.; Rozemuller, A. J.; Hoozemans, J. J.; Veerhuis, R.; van Gool, W. A.

      2000-01-01

      In Alzheimer disease brains, the amyloid plaques are closely associated with a locally induced, nonimmune-mediated, chronic inflammatory response without any apparent influx of leukocytes from the blood. The present findings indicate that in cerebral A beta diseases (Alzheimer disease, Down

    9. Towards spatial frequency domain optical imaging of neurovascular coupling in a mouse model of Alzheimer's disease

      Science.gov (United States)

      Lin, Alexander J.; Konecky, Soren D.; Rice, Tyler B.; Green, Kim N.; Choi, Bernard; Durkin, Anthony J.; Tromberg, Bruce J.

      2012-02-01

      Early neurovascular coupling (NVC) changes in Alzheimer's disease can potentially provide imaging biomarkers to assist with diagnosis and treatment. Previous efforts to quantify NVC with intrinsic signal imaging have required assumptions of baseline optical pathlength to calculate changes in oxy- and deoxy-hemoglobin concentrations during evoked stimuli. In this work, we present an economical spatial frequency domain imaging (SFDI) platform utilizing a commercially available LED projector, camera, and off-the-shelf optical components suitable for imaging dynamic optical properties. The fast acquisition platform described in this work is validated on silicone phantoms and demonstrated in neuroimaging of a mouse model.

    10. [Nutritional approaches to modulate oxidative stress that induce Alzheimer's disease. Nutritional approaches to prevent Alzheimer's disease].

      Science.gov (United States)

      Lara, Humberto Herman; Alanís-Garza, Eduardo Javier; Estrada Puente, María Fernanda; Mureyko, Lucía Liliana; Alarcón Torres, David Alejandro; Ixtepan Turrent, Liliana

      2015-01-01

      Alzheimer's disease is the most common cause of dementia in the world; symptoms first appear after age 65 and have a progressive evolution. Expecting an increase on its incidence and knowing there is currently no cure for Alzheimer's disease, it is a necessity to prevent progression. The change in diet due to globalization may explain the growth of the incidence in places such as Japan and Mediterranean countries, which used to have fewer incidences. There is a direct correlation between disease progression and the increased intake of alcohol, saturated fats, and red meat. Therefore, we find obesity and higher serum levels in cholesterol due to saturated fat as a result. A way to decrease the progression of Alzheimer's is through a diet rich in polipheno/es (potent antioxidants), unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t, fruits with low glycemic index, and a moderate consumption of red wine. Through this potent antioxidant diet we accomplish the prevention of dementia and the progression of Alzheimer's disease. This article emphasizes the food and other components that have been demonstrated to decrease the oxidative stress related to these progressive diseases.

    11. Networks of tau distribution in Alzheimer's disease.

      Science.gov (United States)

      Hoenig, Merle C; Bischof, Gérard N; Seemiller, Joseph; Hammes, Jochen; Kukolja, Juraj; Onur, Özgür A; Jessen, Frank; Fliessbach, Klaus; Neumaier, Bernd; Fink, Gereon R; van Eimeren, Thilo; Drzezga, Alexander

      2018-02-01

      See Whitwell (doi:10.1093/brain/awy001) for a scientific commentary on this article.A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally connected brain regions. Therefore, we examined whether independent components could be identified in the distribution pattern of in vivo tau pathology and whether these components correspond with specific functional connectivity networks. Twenty-two 18F-AV-1451 PET scans of patients with amnestic Alzheimer's disease (mean age = 66.00 ± 7.22 years, 14 males/eight females) were spatially normalized, intensity standardized to the cerebellum, and z-transformed using the mean and deviation image of a healthy control sample to assess Alzheimer's disease-related tau pathology. First, to detect distinct tau pathology networks, the deviation maps were subjected to an independent component analysis. Second, to investigate if regions of high tau burden are associated with functional connectivity networks, we extracted the region with the maximum z-value in each of the generated tau pathology networks and used them as seeds in a subsequent resting-state functional MRI analysis, conducted in a group of healthy adults (n = 26) who were part of the 1000 Functional Connectomes Project. Third, to examine if tau pathology co-localizes with functional connectivity networks, we quantified the spatial overlap between the seed-based networks and the corresponding tau pathology network by calculating the Dice similarity coefficient. Additionally, we assessed if the tau-dependent seed-based networks correspond with known functional resting-state networks. Finally, we examined the relevance of the identified components in regard to the neuropathological Braak

    12. Alzheimer Center Reina Sofia Foundation: fighting the disease and providing overall solutions.

      Science.gov (United States)

      Martínez-Martín, Pablo; Avila, Jesús

      2010-01-01

      As the impact of Alzheimer's disease (AD) on society expands, the reaction aimed at neutralizing its effects also increases. In Spain, an initiative arisen from the highest institution of the State has launched a crusade for fighting the disease from a multidisciplinary stance. In 2002, the "Alzheimer Project" of the Reina Sofia Foundation was announced and in 2007, the Alzheimer Center Reina Sofia Foundation was inaugurated. This resource includes a long-term inpatient care facility, a day-care center, premises for education and training, and a research unit. This way, patients and investigators share the space in a clear expression of "translational research". The Research Unit is managed by the CIEN Foundation, Carlos III Institute of Health, an entity depending on the Ministry of Science and Innovation, and financed in part by the Reina Sofia Foundation. It includes clinical and social research, laboratory, neuroimaging (MRI 3T), and biobank facilities. The connection of the Unit with other research centers and laboratories (both in Spain and outside), universities, and associations of AD patients' relatives is tight and facilitates a dynamic collaboration. The involvement of all social strata in the Alzheimer Project makes evident the unitary effort that Spain is carrying out in the fight against neurodegenerative diseases and, particularly, AD.

    13. Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

      Directory of Open Access Journals (Sweden)

      Anna E. Blanken

      2017-01-01

      Full Text Available Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD and 7 cognitively normal (NC subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ, tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP.

    14. Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project

      NARCIS (Netherlands)

      Morbelli, S.; Perneczky, R.; Drzezga, A.; Frisoni, G. B.; Caroli, A.; van Berckel, B.N.M.; Ossenkoppele, R.; Guedj, E.; Didic, M.; Brugnolo, A.; Naseri, M.; Sambuceti, G.; Pagani, M.; Nobili, F.

      2013-01-01

      This project aimed to investigate the metabolic basis for resilience to neurodegeneration (cognitive reserve) in highly educated patients with prodromal Alzheimer disease (AD). Methods: Sixty-four patients with amnestic mild cognitive impairment who later converted to AD dementia during follow-up,

    15. Developing novel blood-based biomarkers for Alzheimer's disease

      DEFF Research Database (Denmark)

      Snyder, Heather M; Carrillo, Maria C; Grodstein, Francine

      2014-01-01

      Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue...... of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant...

    16. Therapeutics of Neurotransmitters in Alzheimer's Disease.

      Science.gov (United States)

      Kandimalla, Ramesh; Reddy, P Hemachandra

      2017-01-01

      Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the loss of memory, multiple cognitive impairments and changes in the personality and behavior. Several decades of intense research have revealed that multiple cellular changes are involved in disease process, including synaptic damage, mitochondrial abnormalities and inflammatory responses, in addition to formation and accumulation of amyloid-β (Aβ) and phosphorylated tau. Although tremendous progress has been made in understanding the impact of neurotransmitters in the progression and pathogenesis of AD, we still do not have a drug molecule associated with neurotransmitter(s) that can delay disease process in elderly individuals and/or restore cognitive functions in AD patients. The purpose of our article is to assess the latest developments in neurotransmitters research using cell and mouse models of AD. We also updated the current status of clinical trials using neurotransmitters' agonists/antagonists in AD.

    17. Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease.

      Science.gov (United States)

      Quiroz, Yakeel T; Willment, Kim Celone; Castrillon, Gabriel; Muniz, Martha; Lopera, Francisco; Budson, Andrew; Stern, Chantal E

      2015-01-01

      Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer's disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. To examine whether functional MRI can detect early functional changes associated with scene encoding in a group of presymptomatic presenilin-1 (PSEN1) E280A mutation carriers. Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed a functional MRI scene encoding task and a post-scan subsequent memory test. PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions (hippocampus,parahippocampal formation) during successful scene encoding compared to age-matched non-carriers. Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD.

    18. Diffusion characteristics of the fornix in patients with Alzheimer's disease.

      Science.gov (United States)

      Tang, Shou Xian; Feng, Qing Liang; Wang, Gui Hong; Duan, Shaofeng; Shan, Bao Ci; Dai, Jian Ping

      2017-07-30

      White matter degradation is a major part of the pathogenesis of Alzheimer's disease (AD). The fornix is the predominant outflow tract from the hippocampus, and alterations to its microstructure in patients with AD are still being explored. Diffusion tensor imaging (DTI) is an in vivo neuroimaging technique that can provide unique information about alterations in tissue microstructure, which can indicate underlying neurobiological process at the microstructural level. In this prospective study, DTI was used to assess and analyze the microstructural features of the fornix in subjects with AD (n = 17), mild cognitive impairment (MCI; n = 12) and healthy controls (n = 17). DTI was performed using Explore DTI software and the FSL package. Within the fornix, patients with AD showed decreased fractional anisotropy values and length of fiber tracts of the fornix relative to healthy controls, but higher mean diffusivity values. MCI subjects showed a trend towards elevated mean diffusivity values in the fornix. The data suggest that DTI provides supporting information on the microstructural alteration of the fornix in patients with AD, and that these diffusion characteristics of the fornix may be helpful for the clinical diagnosis of AD. Copyright © 2016. Published by Elsevier B.V.

    19. Exploring Symmetry to Assist Alzheimer's Disease Diagnosis

      Science.gov (United States)

      Illán, I. A.; Górriz, J. M.; Ramírez, J.; Salas-Gonzalez, D.; López, M.; Padilla, P.; Chaves, R.; Segovia, F.; Puntonet, C. G.

      Alzheimer's disease (AD) is a progressive neurodegenerative disorder first affecting memory functions and then gradually affecting all cognitive functions with behavioral impairments and eventually causing death. Functional brain imaging as Single-Photon Emission Computed Tomography (SPECT) is commonly used to guide the clinician's diagnosis. The essential left-right symmetry of human brains is shown to play a key role in coding and recognition. In the present work we explore the implications of this symmetry in AD diagnosis, showing that recognition may be enhanced when considering this latent symmetry.

    20. Alzheimer's disease camouflaged by histrionic personality disorder.

      Science.gov (United States)

      Hellwig, Sabine; Dykierek, Petra; Hellwig, Bernhard; Zwernemann, Stefan; Meyer, Philipp T

      2012-02-01

      A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.

    1. Monoaminergic Neuropathology in Alzheimer's disease

      Science.gov (United States)

      Šimić, Goran; Leko, Mirjana Babić; Wray, Selina; Harrington, Charles; Delalle, Ivana; Jovanov-Milošević, Nataša; Bažadona, Danira; Buée, Luc; de Silva, Rohan; Di Giovanni, Giuseppe; Wischik, Claude; Hof, Patrick R.

      2016-01-01

      None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD. PMID:27084356

    2. [A new definition for Alzheimer's disease].

      Science.gov (United States)

      Dubois, Bruno

      2013-01-01

      In 2007 and 2010, the International Working Group on Research Criteria for Alzheimer's Disease introduced a new conceptual framework that included a diagnostic algorithm covering early prodromal stages. There is a growing consensus that Alzheimer's disease (AD) should be considered as a clinical-biological entity characterized by: i) a well-defined clinical phenotype (an amnestic syndrome of the hippocampal type in typical AD), and ii) biomarkers, especially pathophysiological biomarkers, of the underlying disease process. The IWG criteria created the possibility for AD to be diagnosed prior to the onset of dementia, and also integrated biomarkers into the diagnostic framework. Although these criteria were intended for research purposes, they are increasingly used in expert centers for early diagnosis, for example of young-onset AD and complex cases (posterior cortical atrophy, primary progressive aphasia, etc.), where biomarkers can improve the diagnostic accuracy. In this article we present this new approach, together with the results of ongoing validation studies and data obtained by a French research team.

    3. Prevention of Alzheimer disease: The roles of nutrition and primary care.

      Science.gov (United States)

      Bane, Tabitha J; Cole, Connie

      2015-05-15

      Risk factors for developing Alzheimer disease include hypercholesterolemia, hypertension, obesity, and diabetes. Due to lack of effective treatments for Alzheimer disease, nutrition and primary prevention becomes important.

    4. Frontal presentation of Alzheimer's disease: A series of patients with biological evidence by CSF biomarkers

      Directory of Open Access Journals (Sweden)

      Leonardo Cruz de Souza

      Full Text Available ABSTRACT Besides its typical amnesic presentation, focal atypical presentations of Alzheimer's disease (AD have been described in neuropathological studies. These phenotypical variants of AD (so-called "atypical AD" do not follow the typical amnestic pattern and include non-amnestic focal cortical syndromes, such as posterior cortical atrophy and frontal variant AD. These variants exhibit characteristic histological lesions of Alzheimer pathology at post-mortem exam. By using physiopathological markers, such as cerebrospinal fluid markers, it is now possible to establish in vivo a biological diagnosis of AD in these focal cortical syndromes. We report a series of eight patients who were diagnosed with behavioural variant frontotemporal dementia based on their clinical, neuropsychological and neuroimaging findings, while CSF biomarkers showed an AD biological profile, thus supporting a diagnosis of frontal variant of AD.

    5. [Correlation between Alzheimer disease and cataract].

      Science.gov (United States)

      Liu, S S; Zhu, S Q

      2017-04-11

      Alzheimer disease (AD) is a progressive neurodegenerative disease and is a leading cause of dementia among elders. In the early phase of AD, even if neuropathological changes presented, but little to none clinical symptoms were found. Therefore, it is difficult to diagnose AD in the beginning of the disease. It is vital to find a noninvasive way for both diagnose and prognosis of AD. Studies have found that β-amyloid (Aβ) works as a connection between AD and cataract. This review will discuss AD and its associated markers which may be present in the lens and cataract related AD to provide more basis for early diagnosis of AD. (Chin J Ophthalmol, 2017, 53: 314-316) .

    6. Alzheimer's disease prevention: A way forward.

      Science.gov (United States)

      Bermejo-Pareja, F; Llamas-Velasco, S; Villarejo-Galende, A

      2016-12-01

      This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

    7. Alzheimer's Disease and Exercise: A Literature Review.

      Science.gov (United States)

      Cass, Shane P

      Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs memory and cognitive judgment. It is the leading cause of dementia in late adult life and is associated with a significant social burden and increased morbidity and mortality in the elderly. Because of mixed effectiveness of medications, exercise has been considered as a treatment for pre-clinical AD, late stage AD, and as a prevention strategy. Exercise appears to improve brain blood flow, increase hippocampal volume, and improve neurogenesis. Prospective studies indicate that physical inactivity is one of the most common preventable risk factors for developing AD and that higher physical activity levels are associated with a reduced risk of development of disease. Exercise as a treatment for AD shows improvement in cognitive function, decreased neuropsychiatric symptoms, and a slower decline in activities of daily living (ADL). Exercise has been shown to have fewer side effects and better adherence compared to medications.

    8. Aluminium and Alzheimer's disease: the science that describes the link

      National Research Council Canada - National Science Library

      Exley, Christopher

      2001-01-01

      ... that has been encircled is the gene for the amyloid precursor protein. (Thanks to Walter Lukiw for supplying this information.) Aluminium and Alzheimer's Disease: The Science that Describes the LinkAluminium and Alzheimer's Disease The Science that Describes the Link Edited by Christopher Exley Birchall Centre for Inorganic Chemistry and Materials Scienc...

    9. 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…

    10. 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

      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....

    11. 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....

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

      Science.gov (United States)

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

      2009-01-01

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

    13. 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…

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

      NARCIS (Netherlands)

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

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

    15. [Non-verbal communication in Alzheimer's disease].

      Science.gov (United States)

      Schiaratura, Loris Tamara

      2008-09-01

      This review underlines the importance of non-verbal communication in Alzheimer's disease. A social psychological perspective of communication is privileged. Non-verbal behaviors such as looks, head nods, hand gestures, body posture or facial expression provide a lot of information about interpersonal attitudes, behavioral intentions, and emotional experiences. Therefore they play an important role in the regulation of interaction between individuals. Non-verbal communication is effective in Alzheimer's disease even in the late stages. Patients still produce non-verbal signals and are responsive to others. Nevertheless, few studies have been devoted to the social factors influencing the non-verbal exchange. Misidentification and misinterpretation of behaviors may have negative consequences for the patients. Thus, improving the comprehension of and the response to non-verbal behavior would increase first the quality of the interaction, then the physical and psychological well-being of patients and that of caregivers. The role of non-verbal behavior in social interactions should be approached from an integrative and functional point of view.

    16. Longitudinal morphometric MRI study of Alzheimer's disease

      International Nuclear Information System (INIS)

      Ogomori, Koji; Takano, Koichi; Kuwabara, Yasuo; Nakano, Seigo; Nawata, Hideyuki; Yano, Rika; Nishimura, Ryoji; Takita, Masashi

      2009-01-01

      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)

    17. Disease progression and regression in sporadic small vessel disease-insights from neuroimaging.

      Science.gov (United States)

      van Leijsen, Esther M C; de Leeuw, Frank-Erik; Tuladhar, Anil M

      2017-06-01

      Cerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of dementia. Comprehensive characterization of the time course of disease progression will result in better understanding of aetiology and clinical consequences of SVD. SVD progression has been studied extensively over the years, usually describing change in SVD markers over time using neuroimaging at two time points. As a consequence, SVD is usually seen as a rather linear, continuously progressive process. This assumption of continuous progression of SVD markers was recently challenged by several studies that showed regression of SVD markers. Here, we provide a review on disease progression in sporadic SVD, thereby taking into account both progression and regression of SVD markers with emphasis on white matter hyperintensities (WMH), lacunes and microbleeds. We will elaborate on temporal dynamics of SVD progression and discuss the view of SVD progression as a dynamic process, rather than the traditional view of SVD as a continuous progressive process, that might better fit evidence from longitudinal neuroimaging studies. We will discuss possible mechanisms and clinical implications of a dynamic time course of SVD, with both progression and regression of SVD markers. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

    18. Hypertension is associated with worse cognitive function and hippocampal hypometabolism in Alzheimer's disease.

      Science.gov (United States)

      Moonga, I; Niccolini, F; Wilson, H; Pagano, G; Politis, M

      2017-09-01

      A growing body of evidence suggests that cardiovascular disease risk factors including hypertension may be linked to sporadic Alzheimer's disease (AD). It is well known that hypertension is associated with cerebrovascular disease and vascular dementia on the basis of vascular remodeling. However, the mechanisms linking hypertension and AD remain unclear. We studied 197 patients with AD (86 male; mean age ± SD: 75.8 ± 7.4 years) from the Alzheimer's Disease Neuroimaging Initiative database with (n = 97) and without (n = 100) hypertension. We explored associations between hypertension and clinical, plasma, cerebrospinal fluid and imaging markers of AD pathology in order to elucidate the underlying mechanisms that may link AD and hypertension. We found that patients with AD with hypertension had worse cognitive function (Alzheimer's disease Assessment Scale-cognitive subscale, P = 0.038) and higher neuropsychiatric symptom burden (Neuropsychiatric Inventory Questionnaire, P = 0.016) compared with those without hypertension. Patients with AD with hypertension showed reduced glucose hypometabolism in the right (P symptoms and hippocampal glucose hypometabolism, it is not associated with evidence of increased amyloid or tau pathology. Effective management of hypertension may potentially have a therapeutic role in the alleviation of symptoms in AD. © 2017 EAN.

    19. Comparing 3T and 1.5T MRI for Mapping Hippocampal Atrophy in the Alzheimer’s Disease Neuroimaging Initiative

      Science.gov (United States)

      Chow, N.; Hwang, K.S.; Hurtz, S.; Green, A.E.; Somme, J.H.; Thompson, P.M.; Elashoff, D.A.; Jack, C.R.; Weiner, M.; Apostolova, L.G.

      2018-01-01

      BACKGROUND AND PURPOSE Prior MR imaging studies, primarily at 1.5T, established hippocampal atrophy as a biomarker for Alzheimer disease. 3T MR imaging offers a higher contrast and signal-to-noise ratio, yet distortions and intensity uniformity are harder to control. We applied our automated hippocampal segmentation technique to 1.5T and 3T MR imaging data, to determine whether hippocampal atrophy detection was enhanced at 3T. MATERIALS AND METHODS We analyzed baseline MR imaging data from 166 subjects from the Alzheimer’s Disease Neuroimaging Initiative-1 (37 with Alzheimer disease, 76 with mild cognitive impairment, and 53 healthy controls) scanned at 1.5T and 3T. Using multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for sex. 3D statistical maps were adjusted for multiple comparisons by using permutation-based statistics at a threshold of P < .01. RESULTS Bilaterally significant radial distance differences in the areas corresponding to the cornu ammonis 1, cornu ammonis 2, and subiculum were detected for Alzheimer disease versus healthy controls and mild cognitive impairment versus healthy controls at 1.5T and more profoundly at 3T. Comparison of Alzheimer disease with mild cognitive impairment did not reveal significant differences at either field strength. Subjects who converted from mild cognitive impairment to Alzheimer disease within 3 years of the baseline scan versus nonconverters showed significant differences in the area corresponding to cornu ammonis 1 of the right hippocampus at 3T but not at 1.5T. CONCLUSIONS While hippocampal atrophy patterns in diagnostic comparisons were similar at 1.5T and 3T, 3T showed a superior signal-to-noise ratio and detected atrophy with greater effect size compared with 1.5T. PMID:25614473

    20. [Prevention of dementia (including Alzheimer's disease)].

      Science.gov (United States)

      Kornhuber, H H

      2004-05-01

      Prevention of dementia: Life expectancy still increases linearly, and the elderly part of the European population grows rapidly in relation to the young. Dementia, however, grows even more rapidly, because it increases exponentially after age 65; it will become a great burden if nothing is done. The discussion so far is concentrated on treatment, whereas prevention is neglected. The therapy of dementia, however, has limited effect. Contrary to a widespread opinion prevention is possible. Genetic factors alone dominate the fate of cognition only in about 3 % of the cases. Besides age, lifestyle and the vascular risk factors exercise a great influence. High blood pressure carries a fourfold risk, diabetes more than doubles the risk both of the vascular and of the Alzheimer type; combined even more. Especially cerebral microangiopathy is strongly associated with Alzheimer's dementia, it triggers the vicious circle which leads to amyloid deposition. The importance of the circulation is underestimated, because most of the microvascular cerebral lesions are not perceived by the patient. All the risk factors for Alzheimer's disease after age 65 are also vascular risk factors especially for microangiopathy: Apo-E4, oestrogen deficiency, insulin resistance, diabetes, arterial hypertension, high cholesterol, old age and increased plasma homocystin which is often caused by alcohol consumption even in moderate doses. A healthy life style with daily outdoor activity and a Mediterranean diet not only reduces the risk of dementia, but also of coronary death and cancer. Cognitively stimulating activity protects even more than physical activity against dementia; the basis for this is acquired in youth by education. Therapy with statins is advisable if atherosclerosis cannot be reasonably counteracted by physical activity and diet.

    1. Visual system manifestations of Alzheimer's disease.

      Science.gov (United States)

      Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

      2017-12-01

      Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

    2. Comparing Clinical Profiles in Alzheimer's Disease and Parkinson's Disease Dementia

      Directory of Open Access Journals (Sweden)

      Martin R. Farlow

      2013-09-01

      Full Text Available Background: Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD and Parkinson's disease dementia (PDD may improve the interpretation of drug effects and the design of future studies. Methods: This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD. Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog, Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL scale, 10-item Neuropsychiatric Inventory (NPI-10 and the ADCS-Clinical Global Impression of Change (CGIC was compared [standardized difference (Cohen's d, similar if Results: Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47 and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58 were higher in AD; PDD patients were more impaired in the language (0.23 and praxis (0.34 domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14 and improvement on the NPI-10 (0.11 compared with patients with PDD. Conclusion: Differing patterns of impairment occur in AD and PDD.

    3. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

      Science.gov (United States)

      2011-11-04

      ... disease is a pain they know all too well. Alzheimer's disease burdens an increasing number of our Nation's... who have felt the pain and sorrow brought in its wake. In light of their hardship, let us make every...

    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....

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

      NARCIS (Netherlands)

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

      2008-01-01

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

    6. Recruitment of subjects into clinical trials for Alzheimer disease.

      Science.gov (United States)

      Knebl, Janice A; Patki, Deepti

      2010-09-01

      Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

    7. 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.

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

      International Nuclear Information System (INIS)

      Evans, Matthew C.; Barnes, Josephine; Nielsen, Casper; Clegg, Shona L.; Blair, Melanie; Douiri, Abdel; Boyes, Richard G.; Fox, Nick C.; Kim, Lois G.; Leung, Kelvin K.; Ourselin, Sebastien

      2010-01-01

      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.)

    9. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.

      Science.gov (United States)

      Quiroz, Yakeel T; Budson, Andrew E; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E

      2010-12-01

      The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Twenty carriers of the Alzheimer's-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.

    10. Alzheimer disease and pre-emptive suicide.

      Science.gov (United States)

      Davis, Dena S

      2014-08-01

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

    11. The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

      Science.gov (United States)

      Toga, Arthur W.; Crawford, Karen L.

      2015-01-01

      The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

    12. La enfermedad de Alzheimer en el año 2000 Alzheimer's disease in the year 2000

      Directory of Open Access Journals (Sweden)

      2001-10-01

      Full Text Available This document summarizes a report on the current state of knowledge of the etiology, diagnosis, and treatment of Alzheimer's disease and on the primary research activities carried out in these areas during the year 2000 under the auspices of the National Institute of Aging and other units of the National Institutes of Health (NIH of the United States of America. In research on the etiology of the disease, key areas of attention have included amyloid, presenilins, apolipoprotein E, and other genetic ties; apoptosis; and protein aggregation in other neurodegenerative diseases. With respect to diagnosis, the progress that has been made is analyzed in the areas of neuroimaging and neuropsychological tests, clinical-pathological correlations, and the identification of biological disease markers, with the goal of being able to diagnose the disease before irreversible cognitive and functional deterioration takes place. Research on pharmacological treatment has been centered on three primary concerns: short-term maintenance of cognitive function, disease prevention, and treatment of behavioral symptoms. Another subject of great importance is support for those who provide care for patients. The report also deals with several areas related to research infrastructure and the contributions of other units of the NIH.

    13. Combining Feature Extraction Methods to Assist the Diagnosis of Alzheimer's Disease.

      Science.gov (United States)

      Segovia, F; Górriz, J M; Ramírez, J; Phillips, C

      2016-01-01

      Neuroimaging data as (18)F-FDG PET is widely used to assist the diagnosis of Alzheimer's disease (AD). Looking for regions with hypoperfusion/ hypometabolism, clinicians may predict or corroborate the diagnosis of the patients. Modern computer aided diagnosis (CAD) systems based on the statistical analysis of whole neuroimages are more accurate than classical systems based on quantifying the uptake of some predefined regions of interests (ROIs). In addition, these new systems allow determining new ROIs and take advantage of the huge amount of information comprised in neuroimaging data. A major branch of modern CAD systems for AD is based on multivariate techniques, which analyse a neuroimage as a whole, considering not only the voxel intensities but also the relations among them. In order to deal with the vast dimensionality of the data, a number of feature extraction methods have been successfully applied. In this work, we propose a CAD system based on the combination of several feature extraction techniques. First, some commonly used feature extraction methods based on the analysis of the variance (as principal component analysis), on the factorization of the data (as non-negative matrix factorization) and on classical magnitudes (as Haralick features) were simultaneously applied to the original data. These feature sets were then combined by means of two different combination approaches: i) using a single classifier and a multiple kernel learning approach and ii) using an ensemble of classifier and selecting the final decision by majority voting. The proposed approach was evaluated using a labelled neuroimaging database along with a cross validation scheme. As conclusion, the proposed CAD system performed better than approaches using only one feature extraction technique. We also provide a fair comparison (using the same database) of the selected feature extraction methods.

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

      International Nuclear Information System (INIS)

      Matsuda, Hiroshi

      2001-01-01

      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. Robust gene dysregulation in Alzheimer's disease brains.

      Science.gov (United States)

      Feng, Xuemei; Bai, Zhouxian; Wang, Jiajia; Xie, Bin; Sun, Jiya; Han, Guangchun; Song, Fuhai; Crack, Peter J; Duan, Yong; Lei, Hongxing

      2014-01-01

      The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional "cushion" for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).

    16. Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

      Science.gov (United States)

      Chen, C; Homma, A; Mok, V C T; Krishnamoorthy, E; Alladi, S; Meguro, K; Abe, K; Dominguez, J; Marasigan, S; Kandiah, N; Kim, S Y; Lee, D Y; De Silva, H A; Yang, Y-H; Pai, M-C; Senanarong, V; Dash, A

      2016-10-01

      There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease. © 2016 The Association for the Publication of the Journal of Internal Medicine.

    17. Support Group Counseling for Caregivers of Alzheimer's Disease Patients.

      Science.gov (United States)

      Hinkle, J. Scott

      1991-01-01

      Describes Alzheimer's disease and the burdens that caregivers encounter in dealing with Alzheimer's patients. Presents information concerning support group counseling for caregivers, their particular needs, and special family issues. Emphasizes that relationships between caregivers and support group counselors are crucial to successful…

    18. International Work Group Criteria for the Diagnosis of Alzheimer Disease

      NARCIS (Netherlands)

      Cummings, J.L.; Dubois, B; Molinuevo, J.L.; Scheltens, P.

      2013-01-01

      Alzheimer-type biomarker changes are identifiable in asymptomatic and mildly symptomatic predementia phases of Alzheimer disease (AD) and AD dementia. The International Work Group (IWG) guidelines for diagnosis identify a unified spectrum of 3 phases. The classic clinical feature that indicates AD

    19. 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......, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts....... Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p

    20. Developing therapeutic vaccines against Alzheimer's disease.

      Science.gov (United States)

      Wisniewski, Thomas; Drummond, Eleanor

      2016-01-01

      Alzheimer's disease (AD) is the most common form of dementia worldwide. It is characterized by an imbalance between the production and clearance of amyloid β (Aβ) and tau proteins. In AD these normal proteins accumulate, leading to aggregation and a conformational change forming oligomeric and fibrillary species with a high β-sheet content. Active and passive immunotherapeutic approaches result in dramatic reduction of Aβ pathology in AD animal models. However, there is much more limited evidence in human studies of significant clinical benefits from these strategies and it is becoming apparent that they may only be effective very early in AD. Vaccination targeting only tau pathology has shown benefits in some mouse studies but human studies are limited. Greater therapeutic efficacy for the next generation of vaccine approaches will likely benefit from specifically targeting the most toxic species of Aβ and tau, ideally simultaneously.

    1. New Acetylcholinesterase Inhibitors for Alzheimer's Disease

      Directory of Open Access Journals (Sweden)

      Mona Mehta

      2012-01-01

      Full Text Available Acetylcholinesterase (AChE remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

    2. Nutrition and the Risk of Alzheimer's Disease

      Directory of Open Access Journals (Sweden)

      Nan Hu

      2013-01-01

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

    3. Implicit memory for music in Alzheimer's disease.

      Science.gov (United States)

      Halpern, A R; O'Connor, M G

      2000-07-01

      Short, unfamiliar melodies were presented to young and older adults and to Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The explicit task was yes-no recognition, and the implicit task was pleasantness ratings, in which memory was shown by higher ratings for old versus new melodies (the mere exposure effect). Young adults showed retention of the melodies in both tasks. Older adults showed little explicit memory but did show the mere exposure effect. The AD patients showed neither. The authors considered and rejected several artifactual reasons for this null effect in the context of the many studies that have shown implicit memory among AD patients. As the previous studies have almost always used the visual modality for presentation, they speculate that auditory presentation, especially of nonverbal material, may be compromised in AD because of neural degeneration in auditory areas in the temporal lobes.

    4. 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.

    5. Resveratrol and Alzheimer's Disease: Mechanistic Insights.

      Science.gov (United States)

      Ahmed, Touqeer; Javed, Sehrish; Javed, Sana; Tariq, Ameema; Šamec, Dunja; Tejada, Silvia; Nabavi, Seyed Fazel; Braidy, Nady; Nabavi, Seyed Mohammad

      2017-05-01

      Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by progressive cognitive and memory deficits. The pathological hallmarks of AD include extracellular senile plaques and intracellular neurofibrillary tangles. Although several mechanisms have been used to explain the underlying pathogenesis of AD, current treatment regimens remain inadequate. The neuroprotective effects of the polyphenolic stilbene resveratrol (3,5,4'-trihydroxy-trans-stilbene) have been investigated in several in vitro and in vivo models of AD. The current review discusses the multiple potential mechanisms of action of resveratrol on the pathobiology of AD. Moreover, due to the limited pharmacokinetic parameters of resveratrol, multiple strategies aimed at increasing the bioavailability of resveratrol have also been addressed.

    6. DNA methylation alterations in Alzheimer's disease.

      Science.gov (United States)

      Yokoyama, Amy S; Rutledge, John C; Medici, Valentina

      2017-05-01

      The observation that Alzheimer's disease (AD) patients with similar and even identical genetic backgrounds often present with heterogeneous pathologies has prompted the hypothesis that epigenetics may contribute to AD. While the study of epigenetics encompasses a variety of modifications including histone modifications and non-coding RNAs, much of the research on how epigenetics might impact AD pathology has been focused on DNA methylation. To this end, several studies have characterized DNA methylation alterations in various brain regions of individuals with AD, with conflicting results. This review examines the results of studies analyzing both global and gene-specific DNA methylation changes in AD and also assesses the results of studies analyzing DNA hydroxymethylation in patients with AD.

    7. Diagnostic disclosure in Alzheimer's disease: A review

      Directory of Open Access Journals (Sweden)

      Irina Raicher

      Full Text Available Abstract Although growing, the literature on research into attitudes of general and specialized physicians towards disclosing the diagnosis of dementia and Alzheimer's disease (AD, or the current practice on AD disclosure, remains limited. Moreover, information is also scarce on what caregivers, or indeed patients themselves, wish to know with regard to their diagnosis. The goal of the present article was to present a review of the current available literature on the topic of truth telling in dementia, especially in AD. The studies discussed in this review were mainly conducted in Europe, particularly in the United Kingdom, as well as the United States. Disclosure of AD diagnosis is not a common practice among physicians. In the clinical context, the discussion on diagnosis disclosure can be valuable for improving the care of AD patients and their families.

    8. The Role of PGRN in Alzheimer's Disease.

      Science.gov (United States)

      Jing, Hua; Tan, Meng-Shan; Yu, Jin-Tai; Tan, Lan

      2016-08-01

      Progranulin (PGRN), a multifunctional growth factor expressed in various tissues, is involved in a diversity of physiologic and pathological processes, including cell proliferation, wound healing, and modulation of inflammation. Interest in the role of progranulin in the brain has increased dramatically since mutations in GRN, which encodes for the protein PGRN, are associated with the pathogenesis of Alzheimer's disease (AD). A great many of studies suggest that PGRN participates in AD pathogenesis through diverse pathways, including Aβ deposition and clearance, intraneuronal deposition of phosphorylated tau, neuroinflammation, and neuronal survival. Decreased GRN mRNA levels can be detected in the parietal lobe of patients clinically diagnosed with AD; more importantly, emerging data support that serum or plasma PGRN can act as a biomarker for AD. By understanding PGRN in a wider context, we may be better able to depict its role in AD and then provide a therapeutic strategy for AD.

    9. Ophthalmic examination in early diagnosis of Alzheimer's disease

      Directory of Open Access Journals (Sweden)

      Xin Li

      2018-02-01

      Full Text Available Alzheimer's disease is a progressive neurodegenerative disorder causing irreversible deterioration in memory and loss of self-care ability, which is seriously affecting the quality of life. There is no cure for Alzheimer's disease. Medication only can control the progression of the disease. Early diagnosis and control of disease progress is of great significance in improving the quality of life of the patients and reducing the burden of family and society. Ophthalmic examination is seen as a window which can “see” brain directly, and some changes in the eye can reflect the changes of the brain most directly. This paper reviews the ophthalmic examination of Alzheimer's disease, including optical coherence tomography(OCT, visual field, contrast sensitivity and eye movements, et al. We hope to provide a new idea for the early diagnosis of Alzheimer's disease.

    10. Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.

      Science.gov (United States)

      Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M; Madison, Cindee M; Haense, Cathleen; Herholz, Karl; Reiman, Eric M; Jagust, William J; Frisoni, Giovanni B

      2015-01-01

      The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.

    11. Role of physical exercise in Alzheimer's disease.

      Science.gov (United States)

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

      2016-04-01

      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 neurofibrillary tangles of the protein tau, brain atrophy and dementia. The beneficial effects of physical exercise have been observed on the maintenance of brain size and efficiency for the prevention of AD risks, such as obesity, hypertension and stroke. These effects are extended to individuals with, or at risk of dementia and other age-related neurodegenerative disorders. Accordingly, although extensive studies are required to fully understand the mechanisms by which physical exercise procures beneficial effects, data suggest the relevance of integrating physical exercise in the prevention and/or cure of AD, disease whose incidence is predicted to increase in the future. Such an increase, may pose medical, social and economical challenges for populations and the health care system worldwide. In the present review we assess the positive aspects of physical exercise with regard to prevention and cure of AD.

    12. Role of physical exercise in Alzheimer's disease

      Science.gov (United States)

      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 neurofibrillary tangles of the protein tau, brain atrophy and dementia. The beneficial effects of physical exercise have been observed on the maintenance of brain size and efficiency for the prevention of AD risks, such as obesity, hypertension and stroke. These effects are extended to individuals with, or at risk of dementia and other age-related neurodegenerative disorders. Accordingly, although extensive studies are required to fully understand the mechanisms by which physical exercise procures beneficial effects, data suggest the relevance of integrating physical exercise in the prevention and/or cure of AD, disease whose incidence is predicted to increase in the future. Such an increase, may pose medical, social and economical challenges for populations and the health care system worldwide. In the present review we assess the positive aspects of physical exercise with regard to prevention and cure of AD. PMID:27073621

    13. Building a roadmap for developing combination therapies for Alzheimer's disease.

      Science.gov (United States)

      Perry, Daniel; Sperling, Reisa; Katz, Russell; Berry, Donald; Dilts, David; Hanna, Debra; Salloway, Stephen; Trojanowski, John Q; Bountra, Chas; Krams, Michael; Luthman, Johan; Potkin, Steven; Gribkoff, Val; Temple, Robert; Wang, Yaning; Carrillo, Maria C; Stephenson, Diane; Snyder, Heather; Liu, Enchi; Ware, Tony; McKew, John; Fields, F Owen; Bain, Lisa J; Bens, Cynthia

      2015-03-01

      Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

    14. Vagus nerve stimulation in patients with Alzheimer's disease

      DEFF Research Database (Denmark)

      Merrill, Charley A; Jonsson, Michael A G; Minthon, Lennart

      2006-01-01

      BACKGROUND: Cognitive-enhancing effects of vagus nerve stimulation (VNS) have been reported during 6 months of treatment in a pilot study of patients with Alzheimer's disease (AD). Data through 1 year of VNS (collected from June 2000 to September 2003) are now reported. METHOD: All patients (N = 17......) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. Responder rates for the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State...

    15. Alzheimer’s Disease Deaths

      Centers for Disease Control (CDC) Podcasts

      2017-05-25

      Dr. Christopher Taylor of CDC’s Alzheimer’s Disease and Healthy Aging Program describes Alzheimer’s disease, the fifth leading cause of death in Americans 65 years and older.  Created: 5/25/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/25/2017.

    16. Perception of Alzheimer Disease in Iranian Traditional Medicine.

      Science.gov (United States)

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

      2016-03-01

      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. 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. 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. 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.

    17. Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer?s disease

      OpenAIRE

      Chen, Po-Ting; Chen, Zih-ten; Hou, Wen-Chi; Yu, Lung-Chih; Chen, Rita P.-Y.

      2016-01-01

      Neprilysin (NEP) is the most important A?-degrading enzyme. Its expression level decreases with age and inversely correlated with amyloid accumulation, suggesting its correlation with the late-onset of Alzheimer?s disease. Recently, many reports showed that upregulating NEP level is a promising strategy in the prevention and therapy of Alzheimer?s disease. Here, we used a sensitive fluorescence-based A? digestion assay to screen 25 curcumin analogs for their ability to upregulate NEP activity...

    18. NEUROIMAGING AND PATTERN RECOGNITION TECHNIQUES FOR AUTOMATIC DETECTION OF ALZHEIMER’S DISEASE: A REVIEW

      Directory of Open Access Journals (Sweden)

      Rupali Kamathe

      2017-08-01

      Full Text Available Alzheimer’s disease (AD is the most common form of dementia with currently unavailable firm treatments that can stop or reverse the disease progression. A combination of brain imaging and clinical tests for checking the signs of memory impairment is used to identify patients with AD. In recent years, Neuroimaging techniques combined with machine learning algorithms have received lot of attention in this field. There is a need for development of automated techniques to detect the disease well before patient suffers from irreversible loss. This paper is about the review of such semi or fully automatic techniques with detail comparison of methods implemented, class labels considered, data base used and the results obtained for related study. This review provides detailed comparison of different Neuroimaging techniques and reveals potential application of machine learning algorithms in medical image analysis; particularly in AD enabling even the early detection of the disease- the class labelled as Multiple Cognitive Impairment.

    19. [Ageing and Alzheimer disease - system dynamics model prediction].

      Science.gov (United States)

      Tomášková, Hana; Kühnová, Jitka; Kuča, Kamil

      The aim of the paper is to describe asystem dynamics model applied on aprediction of the number of patients with Alzheimers disease in the EU in the future and related financial impacts. Dementia resulting from Alzheimers disease is the most widely spread type of dementia and is highly connected with the age of the person - the patient. Most people are diagnosed with Alzheimers disease when they are older than 64. The ageing of population will be an ongoing problem in the next few decades due to alow birth rate and increasing life expectancy. This is areason to focus on prediction models of Alzheimers disease and its impact on economy. The paper presents adynamic modelling approach of system dynamics. The created model of the EU population and patients with AD is expanded by afinancial submodel at the end. This submodel estimates the cost on patients from three available cost studies.Key words: systém dynamic Alzhimers disease population ageing.

    20. 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. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

    1. Speech and orofacial apraxias in Alzheimer's disease.

      Science.gov (United States)

      Cera, Maysa Luchesi; Ortiz, Karin Zazo; Bertolucci, Paulo Henrique Ferreira; Minett, Thaís Soares Cianciarullo

      2013-10-01

      Alzheimer's disease (AD) affects not only memory but also other cognitive functions, such as orientation, language, praxis, attention, visual perception, or executive function. Most studies on oral communication in AD focus on aphasia; however, speech and orofacial apraxias are also present in these patients. The aim of this study was to investigate the presence of speech and orofacial apraxias in patients with AD with the hypothesis that apraxia severity is strongly correlated with disease severity. Ninety participants in different stages of AD (mild, moderate, and severe) underwent the following assessments: Clinical Dementia Rating, Mini-Mental State Examination, Lawton Instrumental Activities of Daily Living, a specific speech and orofacial praxis assessment, and the oral agility subtest of the Boston diagnostic aphasia examination. The mean age was 80.2 ± 7.2 years and 73% were women. Patients with AD had significantly lower scores than normal controls for speech praxis (mean difference=-2.9, 95% confidence interval (CI)=-3.3 to -2.4) and orofacial praxis (mean difference=-4.9, 95% CI=-5.4 to -4.3). Dementia severity was significantly associated with orofacial apraxia severity (moderate AD: β =-19.63, p= 0.011; and severe AD: β =-51.68, p speech apraxia severity (moderate AD: β = 7.07, p = 0.001; and severe AD: β =8.16, p Speech and orofacial apraxias were evident in patients with AD and became more pronounced with disease progression.

    2. Prototype learning and dissociable categorization systems in Alzheimer's disease.

      Science.gov (United States)

      Heindel, William C; Festa, Elena K; Ott, Brian R; Landy, Kelly M; Salmon, David P

      2013-08-01

      Recent neuroimaging studies suggest that prototype learning may be mediated by at least two dissociable memory systems depending on the mode of acquisition, with A/Not-A prototype learning dependent upon a perceptual representation system located within posterior visual cortex and A/B prototype learning dependent upon a declarative memory system associated with medial temporal and frontal regions. The degree to which patients with Alzheimer's disease (AD) can acquire new categorical information may therefore critically depend upon the mode of acquisition. The present study examined A/Not-A and A/B prototype learning in AD patients using procedures that allowed direct comparison of learning across tasks. Despite impaired explicit recall of category features in all tasks, patients showed differential patterns of category acquisition across tasks. First, AD patients demonstrated impaired prototype induction along with intact exemplar classification under incidental A/Not-A conditions, suggesting that the loss of functional connectivity within visual cortical areas disrupted the integration processes supporting prototype induction within the perceptual representation system. Second, AD patients demonstrated intact prototype induction but impaired exemplar classification during A/B learning under observational conditions, suggesting that this form of prototype learning is dependent on a declarative memory system that is disrupted in AD. Third, the surprisingly intact classification of both prototypes and exemplars during A/B learning under trial-and-error feedback conditions suggests that AD patients shifted control from their deficient declarative memory system to a feedback-dependent procedural memory system when training conditions allowed. Taken together, these findings serve to not only increase our understanding of category learning in AD, but to also provide new insights into the ways in which different memory systems interact to support the acquisition of

    3. The future of blood-based biomarkers for Alzheimer's disease

      DEFF Research Database (Denmark)

      Henriksen, Kim; O'Bryant, Sid E; Hampel, Harald

      2014-01-01

      Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease...

    4. Cognitive disability in alzheimer's disease and its management.

      Science.gov (United States)

      Corsi, M; Di Raimo, T; Di Lorenzo, C; Rapp-Ricciardi, M; Archer, T; Ricci, S; Businaro, R

      2016-01-01

      Cognitive disability linked to neurodegenerative diseases and in particular to Alzheimer's disease, remains an increasing cause for concern through a dramatic prevalence increment and associated socio-economic burdens. Initially Alzheimer's disease develops asymptomatically with primary clinical signs, such as memory impairment, decline of spatial and perceptual abilities, occurring at a later stage. This delay implies the possibility of promoting early interventions during the pre-symptomatic stage of the disease. Different strategies have been applied in order to prevent/delay onset of Alzheimer's disease or at least to improve quality of life and health conditions of Alzheimer's disease patients and their caregivers, especially in the absence of current viable therapies. Multidomain interventions, aimed at affecting several risk factors simultaneously, offer a versatility that may attain improved outcomes in comparison with single-domain prevention trials. These multidomain interventions involve diet, physical exercise, cognitive training and social activities, while music therapy, improving self-consciousness and reducing neurofibrils, may contribute to deceleration/delay onset of Alzheimer's disease progression. Information and Communication Technology (ICT) provides broad applications to improve quality of life and well-being of Alzheimer's disease patients and caregivers, suffering from psychological distress, as well as reducing additional public health costs.

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

      International Nuclear Information System (INIS)

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

      2012-01-01

      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.

    6. 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.

    7. 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.

    8. 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.

    9. Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer?s disease mouse model

      OpenAIRE

      Nygaard, Haakon B; Kaufman, Adam C; Sekine-Konno, Tomoko; Huh, Linda L; Going, Hilary; Feldman, Samantha J; Kostylev, Mikhail A; Strittmatter, Stephen M

      2015-01-01

      Introduction Recent studies have shown that several strains of transgenic Alzheimer?s disease (AD) mice overexpressing the amyloid precursor protein (APP) have cortical hyperexcitability, and their results have suggested that this aberrant network activity may be a mechanism by which amyloid-? (A?) causes more widespread neuronal dysfunction. Specific anticonvulsant therapy reverses memory impairments in various transgenic mouse strains, but it is not known whether reduction of epileptiform a...

    10. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

      NARCIS (Netherlands)

      McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; Mohs, R.C.; Morris, J.C.; Rossor, M.N.; Scheltens, P.; Carrillo, M.C.; Thies, B.; Weintraub, S.; Phelps, C.H.

      2011-01-01

      The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers

    11. Deep Learning based Classification of FDG-PET Data for Alzheimers Disease Categories.

      Science.gov (United States)

      Singh, Shibani; Srivastava, Anant; Mi, Liang; Caselli, Richard J; Chen, Kewei; Goradia, Dhruman; Reiman, Eric M; Wang, Yalin

      2017-10-01

      Fluorodeoxyglucose (FDG) positron emission tomography (PET) measures the decline in the regional cerebral metabolic rate for glucose, offering a reliable metabolic biomarker even on presymptomatic Alzheimer's disease (AD) patients. PET scans provide functional information that is unique and unavailable using other types of imaging. However, the computational efficacy of FDG-PET data alone, for the classification of various Alzheimers Diagnostic categories, has not been well studied. This motivates us to correctly discriminate various AD Diagnostic categories using FDG-PET data. Deep learning has improved state-of-the-art classification accuracies in the areas of speech, signal, image, video, text mining and recognition. We propose novel methods that involve probabilistic principal component analysis on max-pooled data and mean-pooled data for dimensionality reduction, and multilayer feed forward neural network which performs binary classification. Our experimental dataset consists of baseline data of subjects including 186 cognitively unimpaired (CU) subects, 336 mild cognitive impairment (MCI) subjects with 158 Late MCI and 178 Early MCI, and 146 AD patients from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We measured F1-measure, precision, recall, negative and positive predictive values with a 10-fold cross validation scheme. Our results indicate that our designed classifiers achieve competitive results while max pooling achieves better classification performance compared to mean-pooled features. Our deep model based research may advance FDG-PET analysis by demonstrating their potential as an effective imaging biomarker of AD.

    12. Deep-learning-based classification of FDG-PET data for Alzheimer's disease categories

      Science.gov (United States)

      Singh, Shibani; Srivastava, Anant; Mi, Liang; Caselli, Richard J.; Chen, Kewei; Goradia, Dhruman; Reiman, Eric M.; Wang, Yalin

      2017-11-01

      Fluorodeoxyglucose (FDG) positron emission tomography (PET) measures the decline in the regional cerebral metabolic rate for glucose, offering a reliable metabolic biomarker even on presymptomatic Alzheimer's disease (AD) patients. PET scans provide functional information that is unique and unavailable using other types of imaging. However, the computational efficacy of FDG-PET data alone, for the classification of various Alzheimers Diagnostic categories, has not been well studied. This motivates us to correctly discriminate various AD Diagnostic categories using FDG-PET data. Deep learning has improved state-of-the-art classification accuracies in the areas of speech, signal, image, video, text mining and recognition. We propose novel methods that involve probabilistic principal component analysis on max-pooled data and mean-pooled data for dimensionality reduction, and multilayer feed forward neural network which performs binary classification. Our experimental dataset consists of baseline data of subjects including 186 cognitively unimpaired (CU) subjects, 336 mild cognitive impairment (MCI) subjects with 158 Late MCI and 178 Early MCI, and 146 AD patients from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We measured F1-measure, precision, recall, negative and positive predictive values with a 10-fold cross validation scheme. Our results indicate that our designed classifiers achieve competitive results while max pooling achieves better classification performance compared to mean-pooled features. Our deep model based research may advance FDG-PET analysis by demonstrating their potential as an effective imaging biomarker of AD.

    13. Mediterranean diet and Alzheimer disease mortality

      Science.gov (United States)

      Scarmeas, Nikolaos; Luchsinger, Jose A.; Mayeux, Richard; Stern, Yaakov

      2009-01-01

      Background We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. Objectives To examine the association between MeDi and mortality in patients with AD. Methods A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. Results Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003). Conclusion Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect. PMID:17846408

    14. Automatic classification of MR scans in Alzheimer's disease

      OpenAIRE

      García, Fernando Pérez; uk, fernando perezgarcia ucl ac

      2018-01-01

      Presentation of the paper "Automatic classification of MR scans in Alzheimer's disease" by Klöppel et al. for the journal club of the Centre for Doctoral Training in Medical Image Computing at University College London.

    15. 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.

    16. 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...

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

      DEFF Research Database (Denmark)

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

      2004-01-01

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

    18. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

      OpenAIRE

      Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

      2016-01-01

      Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and ana...

    19. New Perspectives on Alzheimer's Disease and Nutrition.

      Science.gov (United States)

      Gustafson, Deborah R; Clare Morris, Martha; Scarmeas, Nikolaos; Shah, Raj C; Sijben, John; Yaffe, Kristine; Zhu, Xiongwei

      2015-01-01

      Accumulating evidence shows nutritional factors influence the risk of developing Alzheimer's disease (AD) and its rate of clinical progression. Dietary and lifestyle guidelines to help adults reduce their risk have been developed. However, the clinical dementia picture remains complex, and further evidence is required to demonstrate that modifying nutritional status can protect the brain and prevent, delay, or reduce pathophysiological consequences of AD. Moreover, there is a pressing need for further research because of the global epidemic of overweight and obesity combined with longer life expectancy of the general population and generally observed decreases in body weight with aging and AD. A new research approach is needed, incorporating more sophisticated models to account for complex scenarios influencing the relationship between nutritional status and AD. Systematic research should identify and address evidence gaps. Integrating longitudinal epidemiological data with biomarkers of disease, including brain imaging technology, and randomized controlled interventions may provide greater insights into progressive and subtle neurological changes associated with dietary factors in individuals at risk for or living with AD. In addition, greater understanding of mechanisms involved in nutritional influences on AD risk and progression, such as oxidative stress and loss of neuronal membrane integrity, will better inform possible interventional strategies. There is consensus among the authors that nutritional deficits, and even states of excess, are associated with AD, but more work is needed to determine cause and effect. Appropriately designed diets or nutritional interventions may play a role, but additional research is needed on their clinical-cognitive effectiveness.

    20. Physical activity and Alzheimer disease course.

      Science.gov (United States)

      Scarmeas, Nikolaos; Luchsinger, Jose A; Brickman, Adam M; Cosentino, Stephanie; Schupf, Nicole; Xin-Tang, Ming; Gu, Yian; Stern, Yaakov

      2011-05-01

      To examine the association between physical activity (PA) and Alzheimer disease (AD) course. PA has been related to lower risk for AD. Whether PA is associated with subsequent AD course has not been investigated. In a population-based study of individuals aged 65 years and older in New York who were prospectively followed up with standard neurologic and neuropsychological evaluations (every ~1.5 years), 357 participants i) were nondemented at baseline and ii) were diagnosed with AD during follow-up (incident AD). PA (sum of participation in a variety of physical activities, weighted by the type of activity [light, moderate, and severe]) obtained 2.4 (standard deviation [SD], 1.9) years before incidence was the main predictor of mortality in Cox models and of cognitive decline in generalized estimating equation models that were adjusted for age, gender, ethnicity, education, comorbidities, and duration between PA evaluation and dementia onset. One hundred fifty incident AD cases (54%) died during the course of 5.2 (SD, 4.4) years of follow-up. When compared with incident AD cases who were physically inactive, those with some PA had lower mortality risk, whereas incident AD participants with much PA had an even lower risk. Additional adjustments for apolipoprotein genotype, smoking, comorbidity index, and cognitive performance did not change the associations. PA did not affect rates of cognitive or functional decline. Exercise may affect not only risk for AD but also subsequent disease duration: more PA is associated with prolonged survival in AD.

    1. Emotion and Destination Memory in Alzheimer's Disease.

      Science.gov (United States)

      El Haj, Mohamad; Raffard, Stephane; Antoine, Pascal; Gely-Nargeot, Marie-Christine

      2015-01-01

      Research shows beneficial effect of emotion on self-related information in patients with Alzheimer's Disease (AD). Our paper investigates whether emotion improves destination memory (e.g., did I tell you about the manuscript?), which is thought to be self-related (e.g., did I tell you about the manuscript?). To this aim, twenty-seven AD patients and thirty healthy older adults told 24 neutral facts to eight neutral faces, eight positive faces, and eight negative faces. On a subsequent recognition task, participants had to decide whether they had previously told a given fact to a given face or not. Data revealed no emotional effect on destination memory in AD patients. However, in healthy older adults, better destination memory was observed for negative faces than for positive faces, and the latter memory was better than for neutral faces. The absence of emotional effect on destination memory in AD is interpreted in terms of substantial decline in this memory in the disease.

    2. Involvement of oxidative stress in Alzheimer disease.

      Science.gov (United States)

      Nunomura, Akihiko; Castellani, Rudy J; Zhu, Xiongwei; Moreira, Paula I; Perry, George; Smith, Mark A

      2006-07-01

      Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD, namely, metabolic, mitochondrial, metal, and cell-cycle abnormalities. Contrary to the commonly held notion that pathologic hallmarks of AD signify etiology, several lines of evidence now indicate that aggregation of amyloid-beta and tau is a compensatory response to underlying oxidative stress. Therefore, removal of proteinaceous accumulations may treat the epiphenomenon rather than the disease and may actually enhance oxidative damage. Although some antioxidants have been shown to reduce the incidence of AD, the magnitude of the effect may be modified by individual factors such as genetic predisposition (e.g. apolipoprotein E genotype) and habitual behaviors. Because caloric restriction, exercise, and intellectual activity have been experimentally shown to promote neuronal survival through enhancement of endogenous antioxidant defenses, a combination of dietary regimen of low total calorie and rich antioxidant nutrients and maintaining physical and intellectual activities may ultimately prove to be one of the most efficacious strategies for AD prevention.

    3. Feelings without memory in Alzheimer disease.

      Science.gov (United States)

      Guzmán-Vélez, Edmarie; Feinstein, Justin S; Tranel, Daniel

      2014-09-01

      Patients with Alzheimer disease (AD) typically have impaired declarative memory as a result of hippocampal damage early in the disease. Far less is understood about AD's effect on emotion. We investigated whether feelings of emotion can persist in patients with AD, even after their declarative memory for what caused the feelings has faded. A sample of 17 patients with probable AD and 17 healthy comparison participants (case-matched for age, sex, and education) underwent 2 separate emotion induction procedures in which they watched film clips intended to induce feelings of sadness or happiness. We collected real-time emotion ratings at baseline and at 3 post-induction time points, and we administered a test of declarative memory shortly after each induction. As expected, the patients with AD had severely impaired declarative memory for both the sad and happy films. Despite their memory impairment, the patients continued to report elevated levels of sadness and happiness that persisted well beyond their memory for the films. This outcome was especially prominent after the sadness induction, with sustained elevations in sadness lasting for more than 30 minutes, even in patients with no conscious recollection for the films. These findings indicate that patients with AD can experience prolonged states of emotion that persist well beyond the patients' memory for the events that originally caused the emotion. The preserved emotional life evident in patients with AD has important implications for their management and care, and highlights the need for caretakers to foster positive emotional experiences.

    4. 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.

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

      DEFF Research Database (Denmark)

      Vogel, Asmus; Bhattacharya, Suvosree; Waldorff, Frans Boch

      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....

    6. Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET

      DEFF Research Database (Denmark)

      De Leon, Mony J.; Li, Yi; Okamura, Nobuyuki

      2017-01-01

      Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribrif......Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing...

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

      International Nuclear Information System (INIS)

      Gerber, U.; Vogel

      1989-01-01

      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.) [de

    8. 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'. Copyright © 2015 Elsevier Ltd. All rights reserved.

    9. An image processing technique for diagnosis of Alzheimer's disease

      Science.gov (United States)

      Mahmoudian, Massoud; Ebrahimi, Soltan Ahmed; Kiani, Zahra

      2009-01-01

      BACKGROUND: Patients with Alzheimer's disease (AD) reportedly exhibit hypersensitivity to much diluted tropicamide solution (0.005%), a M4 muscarinic receptor antagonist. Therefore intraocular application of 0.005% tropicamide may be useful for screening dementia. The aim of this study was to simplify the pupil response test by using a new image analyzing system, which consists of a cheap, simple, and easy to use web-camera and a computer. METHODS: Intraocular tropicamide of 0.005% concentration was administered in 3 groups: Alzheimer's disease patients (n = 8, average age = 76 ± 5), non-Alzheimer's disease elderly (n = 6, average age = 65 ± 7), and young subjects (n = 8, average age = 28 ± 5). Every 5 minutes for 60 minutes, image of the eye's shape were taken, and the diameter of the pupils was measured. RESULTS: The results showed that differences in pupil dilation rate between Alzheimer's disease and non-Alzheimer's disease subjects were statistically significant. ROC analysis showed that after 35 minutes the sensitivity and specificity of the test were 100%. CONCLUSIONS: Based on our results, we concluded that this recording system might be an appropriate and reliable tool for pupil response diagnosis test of Alzheimer's disease. PMID:21772885

    10. Cell "self-eating" (autophagy) mechanism in Alzheimer's disease.

      Science.gov (United States)

      Funderburk, Sarah F; Marcellino, Bridget K; Yue, Zhenyu

      2010-01-01

      The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-beta plaques. Autophagy has been linked to Alzheimer's disease pathogenesis through its merger with the endosomal-lysosomal system, which has been shown to play a role in the formation of the latter amyloid-beta plaques. However, the precise role of autophagy in Alzheimer's disease pathogenesis is still under contention. One hypothesis is that aberrant autophagy induction results in an accumulation of autophagic vacuoles containing amyloid-beta and the components necessary for its generation, whereas other evidence points to impaired autophagic clearance or even an overall reduction in autophagic activity playing a role in Alzheimer's disease pathogenesis. In this review, we discuss the current evidence linking autophagy to Alzheimer's disease as well as the uncertainty over the exact role and level of autophagic regulation in the pathogenic mechanism of Alzheimer's disease. (c) 2010 Mount Sinai School of Medicine.

    11. Neuroimaging of vascular reserve in patients with cerebrovascular diseases.

      Science.gov (United States)

      Juttukonda, Meher R; Donahue, Manus J

      2017-10-12

      Cerebrovascular reactivity, defined broadly as the ability of brain parenchyma to adjust cerebral blood flow in response to altered metabolic demand or a vasoactive stimulus, is being measured with increasing frequency and may have a use for portending new or recurrent stroke risk in patients with cerebrovascular disease. The purpose of this review is to outline (i) the physiological basis of variations in cerebrovascular reactivity, (ii) available approaches for measuring cerebrovascular reactivity in research and clinical settings, and (iii) clinically-relevant cerebrovascular reactivity findings in the context of patients with cerebrovascular disease, including atherosclerotic arterial steno-occlusion, non-atherosclerotic arterial steno-occlusion, anemia, and aging. Literature references summarizing safety considerations for these procedures and future directions for standardizing protocols and post-processing procedures across centers are presented in the specific context of major unmet needs in the setting of cerebrovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

    12. Follow-up for Alzheimer patients: European Alzheimer Disease Consortium position paper.

      Science.gov (United States)

      Nourhashémi, F; Olde Rikkert, M G; Burns, A; Winblad, B; Frisoni, G B; Fitten, J; Vellas, B

      2010-02-01

      Alzheimer disease (AD) is one of the leading causes of dependence in the elderly. Providing care for patients with AD is complex and the type of care required depends on the stage of the disease and varies over time. The aim of this article is to discuss available care strategies once the AD diagnosis has been made and to propose a follow-up plan as standard of care at a European level. The proposals developed in this article stem from the collaborative work of a panel of multidisciplinary experts involved in the care of AD patients (European Alzheimer Disease Consortium) based on the results of published scientific studies and on their experience from clinical practice. Suggestions for follow-up frequency and easily administered and scored assessment tools are provided, thereby increasing efficiency and quality of care for patients with Alzheimer disease.

    13. A review of neuroimaging findings of apathy in Alzheimer’s Disease

      Science.gov (United States)

      Theleritis, Christos; Politis, Antonios; Siarkos, Kostas; Lyketsos, Costantine G

      2014-01-01

      Background Apathy is one of the most frequent ‘behavioral and psychological signs and symptoms of dementia’ (BPSD) encountered in Alzheimer’s Disease (AD). There is a growing interest in the early diagnosis of apathetic elderly patients in the community since apathy has been associated with reduced daily functioning, caregiver distress, and poor outcome. The generalization of neuroimaging techniques might be able to offer help in this domain. Methods Within this context we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for neuroimaging findings of apathy in Alzheimer’s Disease. Results Neuroimaging findings lend support to the notion that frontal-subcortical networks are involved in the occurrence of apathy in AD. Conclusions Longitudinal studies comparing patients and normal individuals might allow us to infer on the association between apathy and neurodegenerative diseases and what can brain imaging markers tell us about the characterization of this association, thus revealing disease patterns, helping to distinguish clinically distinct cognitive syndromes, and allowing predictions. PMID:24135083

    14. 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…

    15. 3D scattering transforms for disease classification in neuroimaging

      NARCIS (Netherlands)

      Adel, Tameem; Cohen, Taco; Caan, Matthan; Welling, Max

      2017-01-01

      Classifying neurodegenerative brain diseases in MRI aims at correctly assigning discrete labels to MRI scans. Such labels usually refer to a diagnostic decision a learner infers based on what it has learned from a training sample of MRI scans. Classification from MRI voxels separately typically does

    16. Body mass index and risk of Alzheimer's disease

      DEFF Research Database (Denmark)

      Nordestgaard, Liv Tybjærg; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.

      2017-01-01

      between low BMI and high risk of Alzheimer's disease. Design, Setting, and Participants: Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic...... Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP). Main Outcome Measure: Risk of Alzheimer's disease. Results: The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted...... allele score in the CGPS. Using 32 BMIdecreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer's disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1...

    17. My belief or yours? Differential theory of mind deficits in frontotemporal dementia and Alzheimer's disease.

      Science.gov (United States)

      Le Bouc, Raphaël; Lenfant, Pierre; Delbeuck, Xavier; Ravasi, Laura; Lebert, Florence; Semah, Franck; Pasquier, Florence

      2012-10-01

      Theory of mind reasoning-the ability to understand someone else's mental states, such as beliefs, intentions and desires-is crucial in social interaction. It has been suggested that a theory of mind deficit may account for some of the abnormalities in interpersonal behaviour that characterize patients affected by behavioural variant frontotemporal dementia. However, there are conflicting reports as to whether understanding someone else's mind is a key difference between behavioural variant frontotemporal dementia and other neurodegenerative conditions such as Alzheimer's disease. Literature data on the relationship between theory of mind abilities and executive functions are also contradictory. These disparities may be due to underestimation of the fractionation within theory of mind components. A recent theoretical framework suggests that taking someone else's mental perspective requires two distinct processes: inferring someone else's belief and inhibiting one's own belief, with involvement of the temporoparietal and right frontal cortices, respectively. Therefore, we performed a neuropsychological and neuroimaging study to investigate the hypothesis whereby distinct cognitive deficits could impair theory of mind reasoning in patients with Alzheimer's disease and patients with behavioural variant frontotemporal dementia. We used a three-option false belief task to assess theory of mind components in 11 patients with behavioural variant frontotemporal dementia, 12 patients with Alzheimer's disease and 20 healthy elderly control subjects. The patients with behavioural variant frontotemporal dementia and those with Alzheimer's disease were matched for age, gender, education and global cognitive impairment. [(18)F]-fluorodeoxyglucose-positron emission tomography imaging was used to investigate neural correlates of theory of mind reasoning deficits. Performance in the three-option false belief task revealed differential impairments in the components of theory of mind

    18. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

      Science.gov (United States)

      Esopenko, Carrie; Levine, Brian

      2015-02-15

      Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

    19. 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.

    20. Is sporadic Alzheimer's disease a developmental disorder?

      Science.gov (United States)

      Arendt, Thomas; Stieler, Jens; Ueberham, Uwe

      2017-11-01

      Alzheimer's disease (AD) is a neurodegenerative disorder of higher age that specifically occurs in human. Its clinical phase, characterized by a decline in physiological, psychological, and social functioning, is preceded by a long clinically silent phase of at least several decades that might perhaps even start very early in life. Overall, key functional abilities in AD patients decline in reverse order of the development of these abilities during normal childhood and adolescence. Early symptoms of AD, thus, typically affect mental functions that have been acquired only during very recent hominid evolution and as such are specific to human. Neurofibrillar degeneration, a typical neuropathological lesion of the disease and one of the most robust pathological correlates of cognitive impairment, is rarely seen in non-primate mammals and even non-human primates hardly develop a pathology comparable to those seen in AD patients. Neurofibrillar degeneration is not randomly distributed throughout the AD brain. It preferentially affects brain areas that become increasingly predominant during the evolutionary process of encephalization. During progression of the disease, it affects cortical areas in a stereotypic sequence that inversely recapitulates ontogenetic brain development. The specific distribution of cortical pathology in AD, moreover, appears to be determined by the modular organization of the cerebral cortex which basically is a structural reflection of its ontogeny. Here, we summarize recent evidence that phylogenetic and ontogenetic dimensions of brain structure and function provide the key to our understanding of AD. More recent molecular biological studies of the potential pathogenetic role of a genomic mosaic in the brains of patients with AD might even provide arguments for a developmental origin of AD. This article is part of a series "Beyond Amyloid". © 2017 International Society for Neurochemistry.

    1. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease.

      Science.gov (United States)

      Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

      2016-07-01

      Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings.The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed.Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups.Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles.

    2. Combined Creutzfeldt-Jakob/ Alzheimer's Disease Cases are Important in Search for Microbes in Alzheimer's Disease.

      Science.gov (United States)

      Bastian, Frank O

      2017-01-01

      The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD.

    3. Callosal ideomotor apraxia in Alzheimer's disease.

      Science.gov (United States)

      Cimino-Knight, Ann Marie; Gonzalez Rothi, Leslie J; He, Ying; Heilman, Kenneth M

      2017-02-01

      Impaired ability to perform skilled movements with the left upper limb in patients with corpus callosum injury has been well described (callosal apraxia) with some displaying spatial-temporal errors primarily in response to verbal commands (verbal callosal disconnection apraxia), with imitation, and when using actual tools (callosal ideomotor apraxia). Additionally some patients with callosal injury also make content errors when selecting and using the incorrect tool with their left upper limb (callosal conceptual apraxia). Interestingly, patients with Alzheimer's disease (AD) reveal anatomic evidence of callosal degeneration but callosal apraxia in AD has not been described. The purpose of this study was to learn whether patients with AD display forms of callosal apraxia. Participants were 22 right-handed patients with AD and 24 matched controls. Both upper limbs were tested by having subjects pantomime transitive movements to command and imitation. Participants also viewed pictures of an incomplete task and attempted to pantomime the action needed to complete the task. When compared to controls, the participants with AD demonstrated ideomotor and conceptual apraxias of both upper limbs; however, ideomotor apraxia of their left hand was more robust than that of their right hand, suggesting a hemispheric disconnection.

    4. Preclinical Alzheimer disease and risk of falls.

      Science.gov (United States)

      Stark, Susan L; Roe, Catherine M; Grant, Elizabeth A; Hollingsworth, Holly; Benzinger, Tammie L; Fagan, Anne M; Buckles, Virginia D; Morris, John C

      2013-07-30

      We determined the rate of falls among cognitively normal, community-dwelling older adults, some of whom had presumptive preclinical Alzheimer disease (AD) as detected by in vivo imaging of fibrillar amyloid plaques using Pittsburgh compound B (PiB) and PET and/or by assays of CSF to identify Aβ₄₂, tau, and phosphorylated tau. We conducted a 12-month prospective cohort study to examine the cumulative incidence of falls. Participants were evaluated clinically and underwent PiB PET imaging and lumbar puncture. Falls were reported monthly using an individualized calendar journal returned by mail. A Cox proportional hazards model was used to test whether time to first fall was associated with each biomarker and the ratio of CSF tau/Aβ₄₂ and CSF phosphorylated tau/Aβ₄₂, after adjustment for common fall risk factors. The sample (n = 125) was predominately female (62.4%) and white (96%) with a mean age of 74.4 years. When controlled for ability to perform activities of daily living, higher levels of PiB retention (hazard ratio = 2.95 [95% confidence interval 1.01-6.45], p = 0.05) and of CSF biomarker ratios (p fall. Presumptive preclinical AD is a risk factor for falls in older adults. This study suggests that subtle noncognitive changes that predispose older adults to falls are associated with AD and may precede detectable cognitive changes.

    5. Cognitive, functional and behavioral assessment: Alzheimer's disease

      Directory of Open Access Journals (Sweden)

      Márcia L.F. Chaves

      Full Text Available Abstract A review of the evidence on cognitive, functional and behavioral assessment for the diagnosis of dementia due to Alzheimer's disease (AD is presented with revision and broadening of the recommendations on the use of tests and batteries in Brazil for the diagnosis of dementia due to AD. A systematic review of the literature (MEDLINE, LILACS and SCIELO database was carried out by a panel of experts. Studies on the validation and/or adaptation of tests, scales and batteries for the Brazilian population were analyzed and classified according to level of evidence. There were sufficient data to recommend the IQCODE, DAFS-R, DAD, ADL-Q and Bayer scale for the evaluation of instrumental activities of daily living, and the Katz scale for the assessment of basic activities of daily living. For the evaluation of neuropsychiatric symptoms, the Neuropsychiatric Inventory (NPI and the CAMDEX were found to be useful, as was the Cornell scale for depression in dementia. The Mini-Mental State Examination has clinical utility as a screening test, as do the multifunctional batteries (CAMCOG-R, ADAS-COG, CERAD and MDRS for brief evaluations of several cognitive domains. There was sufficient evidence to recommend the CDR scale for clinical and severity assessment of dementia. Tests for Brazilian Portuguese are recommended by cognitive domain based on available data.

    6. CARS microscopy of Alzheimer's diseased brain tissue

      Science.gov (United States)

      Enejder, Annika; Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia-Yi

      2014-02-01

      Alzheimer's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.

    7. Cranial CT frindings of familial Alzheimer's disease

      International Nuclear Information System (INIS)

      Note, Toshiko; Tawara, Satoru; Tsuruta, Kazuhito; Araki, Shukuro

      1982-01-01

      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.)

    8. Deficient symbol processing in Alzheimer disease.

      Science.gov (United States)

      Toepper, Max; Steuwe, Carolin; Beblo, Thomas; Bauer, Eva; Boedeker, Sebastian; Thomas, Christine; Markowitsch, Hans J; Driessen, Martin; Sammer, Gebhard

      2014-01-01

      Symbols and signs have been suggested to improve the orientation of patients suffering from Alzheimer disease (AD). However, there are hardly any studies that confirm whether AD patients benefit from signs or symbols and which symbol characteristics might improve or impede their symbol comprehension. To address these issues, 30 AD patients and 30 matched healthy controls performed a symbol processing task (SPT) with 4 different item categories. A repeated-measures analysis of variance was run to identify impact of different item categories on performance accuracy in both the experimental groups. Moreover, SPT scores were correlated with neuropsychological test scores in a broad range of other cognitive domains. Finally, diagnostic accuracy of the SPT was calculated by a receiver-operating characteristic curve analysis. Results revealed a global symbol processing dysfunction in AD that was associated with semantic memory and executive deficits. Moreover, AD patients showed a disproportional performance decline at SPT items with visual distraction. Finally, the SPT total score showed high sensitivity and specificity in differentiating between AD patients and healthy controls. The present findings suggest that specific symbol features impede symbol processing in AD and argue for a diagnostic benefit of the SPT in neuropsychological assessment.

    9. Potential benefits of phytochemicals against Alzheimer's disease.

      Science.gov (United States)

      Wightman, Emma L

      2017-05-01

      Our current therapeutic drugs for Alzheimer's disease are predominantly derived from the alkaloid class of plant phytochemicals. These drugs, such as galantamine and rivastigmine, attenuate the decline in the cholinergic system but, as the alkaloids occupy the most dangerous end of the phytochemical spectrum (indeed they function as feeding deterrents and poisons to other organisms within the plant itself), they are often associated with unpleasant side effects. In addition, these cholinesterase inhibiting alkaloids target only one system in a disorder, which is typified by multifactorial deficits. The present paper will look at the more benign terpene (such as Ginkgo biloba, Ginseng, Melissa officinalis (lemon balm) and Salvia lavandulaefolia (sage)) and phenolic (such as resveratrol) phytochemicals; arguing that they offer a safer alternative and that, as well as demonstrating efficacy in cholinesterase inhibition, these phytochemicals are able to target other salient systems such as cerebral blood flow, free radical scavenging, anti-inflammation, inhibition of amyloid-β neurotoxicity, glucoregulation and interaction with other neurotransmitters (such as γ-aminobutyric acid) and signalling pathways (e.g. via kinase enzymes).

    10. Epigenetic drug discovery for Alzheimer's disease.

      Science.gov (United States)

      Cacabelos, Ramón; Torrellas, Clara

      2014-09-01

      It is assumed that epigenetic modifications are reversible and could potentially be targeted by pharmacological and dietary interventions. Epigenetic drugs are gaining particular interest as potential candidates for the treatment of Alzheimer's disease (AD). This article covers relevant information from over 50 different epigenetic drugs including: DNA methyltransferase inhibitors; histone deacetylase inhibitors; histone acetyltransferase modulators; histone methyltransferase inhibitors; histone demethylase inhibitors; non-coding RNAs (microRNAs) and dietary regimes. The authors also review the pharmacoepigenomics and the pharmacogenomics of epigenetic drugs. The readers will gain insight into i) the classification of epigenetic drugs; ii) the mechanisms by which these drugs might be useful in AD; iii) the pharmacological properties of selected epigenetic drugs; iv) pharmacoepigenomics and the influence of epigenetic drugs on genes encoding CYP enzymes, transporters and nuclear receptors; and v) the genes associated with the pharmacogenomics of anti-dementia drugs. Epigenetic drugs reverse epigenetic changes in gene expression and might open future avenues in AD therapeutics. Unfortunately, clinical trials with this category of drugs are lacking in AD. The authors highlight the need for pharmacogenetic and pharmacoepigenetic studies to properly evaluate any efficacy and safety issues.

    11. Cortical changes in incipient Alzheimer's disease.

      Science.gov (United States)

      Prestia, Annapaola; Drago, Valeria; Rasser, Paul E; Bonetti, Matteo; Thompson, Paul M; Frisoni, Giovanni B

      2010-01-01

      Mild cognitive impairment (MCI) is defined by memory impairment with no impact on daily activities. 10 to 15% of MCI convert to Alzheimer's disease (AD) per year. While structural changes in the cortex of AD patients have been extensively investigated, fewer studies analyzed changes in the years preceding conversion. 46 MCI patients and 20 healthy controls underwent structural 1.0T-weighted high-resolution MR scans at baseline and after 1.4 (SD 0.3) years. All subjects were assessed yearly for up to 4 years with a comprehensive neuropsychological battery. Sixteen of the 46 patients converted to AD (cMCI) while 30 remained stable (sMCI). An accurate voxel-based statistical mesh-model technique (cortical pattern matching) with a related region-of-interest analysis based on networks defined from a Brodmann area atlas (BAs) were used to map gray matter changes over time. At baseline, cMCI patients had 10 to 30% less cortical gray matter volume than healthy controls in regions known to be affected by AD pathology (entorhinal, temporoparietal, posterior cingulate, and orbitofrontal cortex, p=0.0001). Over time, cMCI patients lost more gray matter than sMCI in all brain areas but mainly in the olfactory and in the polysynaptic hippocampal network (more than 8% gray matter loss, pgray matter loss in the olfactory and polysynaptic hippocampal network. These findings are in line with neuropathological knowledge.

    12. Follow-up for Alzheimer patients: European Alzheimer Disease Consortium position paper.

      NARCIS (Netherlands)

      Nourhashemi, F.; Olde Rikkert, M.G.M.; Burns, A.; Winblad, B.; Frisoni, G.B.; Fitten, J.; Vellas, B.

      2010-01-01

      BACKGROUND AND PURPOSE: Alzheimer disease (AD) is one of the leading causes of dependence in the elderly. Providing care for patients with AD is complex and the type of care required depends on the stage of the disease and varies over time. The aim of this article is to discuss available care

    13. Apathy in Mild Parkinson's Disease: Neuropsychological and Neuroimaging Evidence.

      Science.gov (United States)

      Alzahrani, Hamad; Antonini, Angelo; Venneri, Annalena

      2016-10-19

      Apathy is one of the most common neuropsychiatric symptoms in Parkinson's disease (PD). Few studies have investigated the cognitive and neuroanatomical correlates of apathy in PD, and those which have done so have not controlled for the presence of other neuropsychiatric comorbidities. To explore the cognitive and neuroanatomical correlates of apathy in PD at a mild disease stage. Sixty-five PD patients and 24 healthy controls participated in this study. Patients underwent extensive neuropsychological screening, neuropsychiatric assessment using the Neuropsychiatric Inventory, structural MRI scanning, and neurological examination. Voxel-based independent t-test analyses were used to assess the differences in grey and white matter volumes between the sample groups with/without apathy/neuropsychiatric symptoms. Patients with apathy had lower grey matter volume in several brain areas including the left insula, left inferior/middle/medial frontal gyrus, right anterior cingulate, and the left superior temporal gyrus. Significant impairments were found in tests assessing executive functions, and a trend-level significant difference was observed in long term memory tests in patients with apathy, when compared with patients without apathy. Apathy was associated with greater levels of atrophy in the frontal and temporal cortex, and anterior cingulate, as well as overall lower level of cognitive performance, particularly in executive function and memory skills. Apathy appears to be associated with cognitive impairments in PD, therefore, treatment of this symptom might mitigate its effects on cognitive performance in this clinical population.

    14. Vitamin D and the risk of dementia and Alzheimer disease.

      Science.gov (United States)

      Littlejohns, Thomas J; 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

      2014-09-02

      To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. 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 spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. © 2014 American Academy of Neurology.

    15. Humanin; a defender against Alzheimer's disease?

      Science.gov (United States)

      Matsuoka, Masaaki

      2009-01-01

      Alzheimer's disease (AD) is the most prevalent neurological disease with dementia. AD-related dementia is caused by death and dysfunction of neurons involved in cognitive function. It has been generally believed that increased levels of toxic amyloid-betas (Abetas) are linked to the occurrence of neuronal death as well as dysfunction (Abeta cascade theory). Consequently, lowering levels of toxic Abetas in the brain is considered to be central for therapy of AD. Multiple drug candidates based on this therapeutic strategy have been developed and are being vigorously developed. Some clinical studies have indicated that this strategy is effective. In addition to this theory, Abeta-independent pathomechanisms have been shown to contribute to the progression of AD-related dementia, justifying alternative strategies for AD treatment that are effective against Abeta-independent pathomechanisms. A possible therapeutic strategy belonging to them is to directly suppress AD-related neuronal death and dysfunction. A series of studies indicated that a 24-amino-acid bioactive peptide named Humanin was shown to inhibit neuronal cell death induced by enforced expression of familial AD-related genes. Humanin also protected neurons from being killed by toxic Abetas in vitro. In addition, neuronal dysfunction-associated dementia of mice caused by muscarinic receptor antagonists and intracranially injected toxic Abetas was ameliorated by Humanin therapy. Multiple studies have indicated the existence of a putative specific Humanin receptor on the cell membrane. These results together suggest that an endogenous AD-related humoral factor(s) may inhibit the progression of AD-related dementia by inhibiting both neuronal cell death and dysfunction in vivo. Malfunction of this self-defense mechanism is also hypothesized to be another etiology or an aggravator of AD. Moreover, from a standpoint of AD therapy, stimulation of the AD defense mechanism by a potent Humanin derivative is a promising

    16. 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.

    17. 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.

    18. Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.

      Science.gov (United States)

      Morbelli, Silvia; Drzezga, Alex; Perneczky, Robert; Frisoni, Giovanni B; Caroli, Anna; van Berckel, Bart N M; Ossenkoppele, Rik; Guedj, Eric; Didic, Mira; Brugnolo, Andrea; Sambuceti, Gianmario; Pagani, Marco; Salmon, Eric; Nobili, Flavio

      2012-11-01

      We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration). Copyright © 2012 Elsevier Inc. All rights reserved.

    19. New cardiovascular targets to prevent late onset Alzheimer disease.

      Science.gov (United States)

      Claassen, Jurgen A H R

      2015-09-15

      The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care. Copyright © 2015 Elsevier B.V. All rights reserved.

    20. Aluminium in brain tissue in familial Alzheimer's disease.

      Science.gov (United States)

      Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

      2017-03-01

      The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

    1. Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.

      Science.gov (United States)

      Lieberman, Abraham; Deep, Aman; Shi, Jiong; Dhall, Rohit; Shafer, Saulena; Moguel-Cobos, Guillermo; Dhillon, Ravneet; Frames, Christopher W; McCauley, Margaret

      2018-02-01

      Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD). We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit. Finger displacement was measured by observers not actively involved in the study using a creative grid ruler for all PDD and AD patients. Finger displacement was examined by asking patients to point their index fingers toward the grid ruler with the nails facing upward. Patients were asked to maintain the pointing position for 15 s. After 15 s, patients were asked to close their eyes for another 15 s while maintaining the same position. A positive result was downward index finger displacement of ≥5 cm within the 15-second time window with eyes closed. Of the 56 PDD patients, 53 had bilateral finger displacement of >5 cm. In comparison, of the 35 AD patients, only 1 patient had minimal displacement. Results of the non-invasive finger displacement test may provide insight, on an outpatient basis, of the integrity of subcortical-cortical circuits. Downward finger displacement, especially bilateral downward displacement, may signal the extensive disruption of subcortical-cortical circuits that occurs in PDD patients. AChE: acetylcholinesterase; AD: Alzheimer disease; DLB: dementia with Lewy bodies; ET: essential tremor; MDS-UPDRS: Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale; MMSE: Mini-Mental State Examination; PD: Parkinson disease; PDD: Parkinson disease dementia.

    2. Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network.

      Science.gov (United States)

      Ringman, John M; Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S; Farlow, Martin; Ghetti, Bernardino; McDade, Eric; Masters, Colin L; Mayeux, Richard P; Rossor, Martin; Salloway, Stephen; Schofield, Peter R; Cummings, Jeffrey L; Buckles, Virginia; Bateman, Randall; Morris, John C

      2015-04-01

      Prior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P Alzheimer's disease, we demonstrated increased rates of depression, apathy, and other behavioural symptoms in the mildly symptomatic, prodromal phase of autosomal dominant Alzheimer's disease that

    3. Cognitive rehabilitation in Parkinson's disease: evidence from neuroimaging.

      Science.gov (United States)

      Nombela, Cristina; Bustillo, Pedro J; Castell, Pedro F; Sanchez, Lucía; Medina, Vicente; Herrero, María Trinidad

      2011-01-01

      Cognitive impairment in Parkinson's disease (PD) has received little attention to date and as such, there are currently very few treatment options available. The aim of the present study was to determine whether cognitive training might alleviate these cognitive symptoms and if so, whether such changes might be correlated with altered brain patterns. The performance of 10 PD patients and 10 paired healthy controls was assessed in a modified version of the Stroop task performed in association with functional magnetic resonance imaging, and half of the PD patients were given 6 months of cognitive daily training based on Sudoku exercises. Results showed that the training program improved the cognitive performance in the Stroop test of the trained Parkinson's patients during MRI, specifically in terms of reaction time, and of correct and missing answers. Moreover, training provoked reduced cortical activation patterns with respect to untrained patients that were comparable to the patterns of activation observed in controls. Based on these findings, we propose that cognitive training can contribute significantly to save brain resources in PD patients, maybe by readdressing the imbalance caused by the alterations to inhibitory circuitry. Furthermore, these data strongly support the development and use of standardized cognitive training programs in PD patients.

    4. Cognitive Rehabilitation in Parkinson’s Disease: Evidence from Neuroimaging

      Science.gov (United States)

      Nombela, Cristina; Bustillo, Pedro J.; Castell, Pedro F.; Sanchez, Lucía; Medina, Vicente; Herrero, María Trinidad

      2011-01-01

      Cognitive impairment in Parkinson’s disease (PD) has received little attention to date and as such, there are currently very few treatment options available. The aim of the present study was to determine whether cognitive training might alleviate these cognitive symptoms and if so, whether such changes might be correlated with altered brain patterns. The performance of 10 PD patients and 10 paired healthy controls was assessed in a modified version of the Stroop task performed in association with functional magnetic resonance imaging, and half of the PD patients were given 6 months of cognitive daily training based on Sudoku exercises. Results showed that the training program improved the cognitive performance in the Stroop test of the trained Parkinson’s patients during MRI, specifically in terms of reaction time, and of correct and missing answers. Moreover, training provoked reduced cortical activation patterns with respect to untrained patients that were comparable to the patterns of activation observed in controls. Based on these findings, we propose that cognitive training can contribute significantly to save brain resources in PD patients, maybe by readdressing the imbalance caused by the alterations to inhibitory circuitry. Furthermore, these data strongly support the development and use of standardized cognitive training programs in PD patients. PMID:22203816

    5. The pathological cascade of Alzheimer's disease: The role of inflammation and its therapeutic implications

      NARCIS (Netherlands)

      Hoozemans, Jeroen J. M.; Veerhuis, Robert; Rozemuller, Annemieke J. M.; Eikelenboom, Piet

      2002-01-01

      Alzheimer's disease is a chronic neurodegenerative disease causing progressive impairment of memory and other cognitive functions. A number of sequential events are suggested to be associated with different pathological aspects observed in Alzheimer's disease, the so-called amyloid cascade

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

      Science.gov (United States)

      Arc, Arlington, TX.

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

    7. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial

      OpenAIRE

      Morris, Jill K.; Vidoni, Eric D.; Johnson, David K.; Van Sciver, Angela; Mahnken, Jonathan D.; Honea, Robyn A.; Wilkins, Heather M.; Brooks, William M.; Billinger, Sandra A.; Swerdlow, Russell H.; Burns, Jeffrey M.

      2017-01-01

      Background There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer?s disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. Methods and findings This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control ...

    8. Effect and mechanism of acupuncture on Alzheimer's disease.

      Science.gov (United States)

      Zeng, Bai-Yun; Salvage, Sarah; Jenner, Peter

      2013-01-01

      Alzheimer's disease is the most common form of dementia diagnosed in the aging population worldwide. The cause of Alzheimer's is still not clear. There is no cure for the disease and current treatments are only symptomatic relieve. The search for new treatment is made ever more urgent due to increasing population aging. Acupuncture has been in practice in China for more than 3000 years and used to treat a wide variety of conditions including cardiovascular and psychiatric diseases, acute, and chronic pain. In this chapter, we review recent development on the effects and mechanisms of acupuncture on Alzheimer's disease. In Alzheimer's animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions. The biochemical modulations by acupuncture in the brains of Alzheimer's models are correlated with the cognitive improvement. In Alzheimer's patients, functional brain images demonstrated that acupuncture increased in the activity in the temporal lobe and prefrontal lobe which are related to the memory and cognitive function. Although only a few acupuncture clinical studies with a small number of participants are reported, they represent an important step forward in the research of both acupuncture and Alzheimer's. Translation of acupuncture research in animal model studies into the human subjects will undoubtedly enhance acupuncture efficacy in clinical study and treatment which could eventually lead to a safer, well-tolerated and inexpensive form of care for Alzheimer's patients. © 2013 Elsevier Inc. All rights reserved.

    9. Memory Loss, Alzheimer's Disease and General Anesthesia: A Preoperative Concern.

      Science.gov (United States)

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

      2012-02-20

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

    10. 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 ...

    11. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

      Science.gov (United States)

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

      2006-02-01

      Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

    12. Seizures in dominantly inherited Alzheimer disease.

      Science.gov (United States)

      Zarea, Aline; Charbonnier, Camille; Rovelet-Lecrux, Anne; Nicolas, Gaël; Rousseau, Stéphane; Borden, Alaina; Pariente, Jeremie; Le Ber, Isabelle; Pasquier, Florence; Formaglio, Maite; Martinaud, Olivier; Rollin-Sillaire, Adeline; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Ceccaldi, Mathieu; Gabelle, Audrey; Chamard, Ludivine; Blanc, Frédéric; Sellal, François; Paquet, Claire; Campion, Dominique; Hannequin, Didier; Wallon, David

      2016-08-30

      To assess seizure frequency in a large French cohort of autosomal dominant early-onset Alzheimer disease (ADEOAD) and to determine possible correlations with causative mutations. A national multicentric study was performed in patients with ADEOAD harboring a pathogenic mutation within PSEN1, PSEN2, APP, or a duplication of APP, and a minimal follow-up of 5 years. Clinical, EEG, and imaging data were systematically recorded. We included 132 patients from 77 families: 94 PSEN1 mutation carriers (MCs), 16 APP duplication carriers, 15 APP MCs, and 7 PSEN2 MCs. Seizure frequency was 47.7% after a mean follow-up of 8.4 years (range 5-25). After 5-year follow-up and using a Cox model analysis, the percentages of patients with seizures were respectively 19.1% (10.8%-26.7%) for PSEN1, 28.6% (0%-55.3%) for PSEN2, 31.2% (4.3%-50.6%) for APP duplications, and no patient for APP mutation. APP duplication carriers showed a significantly increased seizure risk compared to both APP MCs (hazard ratio [HR] = 5.55 [95% confidence interval 1.87-16.44]) and PSEN1 MCs (HR = 4.46 [2.11-9.44]). Among all PSEN1 mutations, those within the domains of protein hydrophilic I, transmembrane II (TM-II), TM-III, TM-IV, and TM-VII were associated with a significant increase in seizure frequency compared to other domains (HR = 4.53 [1.93-10.65], p = 0.0005). Seizures are a common feature of ADEOAD. In this population, risk was significantly higher in the APP duplication group than in all other groups. Within PSEN1, 5 specific domains were associated with a higher seizure risk indicating specific correlations between causative mutation and seizures. © 2016 American Academy of Neurology.

    13. Alzheimer's disease: Innate immunity gone awry?

      Science.gov (United States)

      VanItallie, Theodore B

      2017-04-01

      Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline. In contrast, cognitive deficits in AD correlate well with synapse loss. Oligomeric forms of amyloid-beta (oAβs) can be synaptotoxic and evidence of their deposition inside synaptic terminals of cognition-associated neurons explains early memory loss in AD better than formation of extracellular Aβ plaques. Among innate immune cells that reside in the brain, microglia sense danger signals represented by proteins like oAβ and become activated by neuronal damage such as that caused by bacterial endotoxins. The resulting reactive microgliosis has been implicated in generating the chronic form of microglial activation believed to promote AD's development. Genome-wide association studies (GWASs) have yielded data from patients with sporadic AD indicating that its causes include genetic variation in the innate immune system. Recent preclinical studies have reported that β-hydroxybutyrate (βOHB) may protect the brain from the adverse effects of both the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and the deacetylation of histone. Consequently, there is an urgent need for clinical investigations designed to test whether an orally administered βOHB preparation, such as a ketone ester, can have a similar beneficial effect in human subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

    14. Electrochemistry of Alzheimer disease amyloid beta peptides.

      Science.gov (United States)

      Chiorcea-Paquim, Ana-Maria; Enache, Teodor Adrian; Oliveira-Brett, Ana Maria

      2018-02-13

      Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterisation. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation is electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates and protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, in particular zinc, copper, and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

    15. Hypocretin (orexin) loss in Alzheimer's disease.

      Science.gov (United States)

      Fronczek, Rolf; van Geest, Sarita; Frölich, Marijke; Overeem, Sebastiaan; Roelandse, Freek W C; Lammers, Gert Jan; Swaab, Dick F

      2012-08-01

      Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons. The total number of hypocretin-1 immunoreactive neurons was quantified in postmortem hypothalami of AD patients (n = 10) and matched controls (n = 10). In addition, the hypocretin-1 concentration was measured in postmortem ventricular cerebrospinal fluid of 24 AD patients and 25 controls (including the patients and controls in which the hypothalamic cell counts were performed). The number of hypocretin-1 immunoreactive neurons was significantly decreased by 40% in AD patients (median [25th-75th percentiles]); AD 12,935 neurons (9972-19,051); controls 21,002 neurons (16,439-25,765); p = 0.049). Lower cerebrospinal fluid (CSF) hypocretin-1 levels were found in AD patients compared with controls (AD: 275 pg/mL [197-317]; controls: 320 pg/mL [262-363]; p = 0.038). Two AD patients with documented excessive daytime sleepiness showed the lowest CSF hypocretin-1 concentrations (55 pg/mL and 76 pg/mL). We conclude that the hypocretin system is affected in advanced AD. This is reflected in a 40% decreased cell number, and 14% lower CSF hypocretin-1 levels. Copyright © 2012 Elsevier Inc. All rights reserved.

    16. [Prevalence of anosognosia in Alzheimer's disease].

      Science.gov (United States)

      Turró-Garriga, Oriol; Conde-Sala, Josep Lluís; Reñé-Ramírez, Ramón; López-Pousa, Secundino; Gascón-Bayarri, Jordi; Garre-Olmo, Josep

      2014-07-07

      Anosognosia is a disorder that affects the clinical presentation of Alzheimer's disease (AD), increasing in frequency with the evolution of AD. The objective was to determine the prevalence of anosognosia and analyze the associated factors and predictors. Multicenter transversal and observational study of 345 AD patients. Anosognosia was assessed by Anosognosia Questionnaire-Dementia and the evolutionary stage with the Global Deterioration Scale (GDS). Tests used were Mini-Mental State Examination, Disability Assessment for Dementia and Neuropsychiatric Inventory to assess cognition, functional status and neuropsychiatric symptoms, respectively. We adjusted linear regression models to determine the associated variables and binary logistic regression (RLog) to identify predictors of anosognosia. The overall prevalence of anosognosia was 46.7% (95% confidence interval [95% CI] 41.3 to 52.1). The prevalence in stages was 28.4% (GDS 4), 64.6% (GDS 5) and 91.4% (GDS 6). The RLog identified as predictors older age (odds ratio [OR] 1.04; 95% CI 1.01-1.09), lower functional capacity (OR 0.96; 95% CI 0.93-0.98), lower cognitive level (OR 0.9; 95% CI 0.88-0.99), and greater apathy (OR 1.1; 95% CI 1.03-1.18), disinhibition (OR 1.2; 95% CI 1.09-1.50), irritability (OR 1.1; 95% CI 1.09-1.50) and motor disorders (OR 1.2; 95% CI 1.09-1.50). Anosognosia increases with further deterioration. In patients with a mild impairment, predictor variables were apathy, disinhibition and motor disorders. Copyright © 2013 Elsevier España, S.L. All rights reserved.

    17. Alzheimer's Disease and Glaucoma: Imaging the Biomarkers of Neurodegenerative Disease

      Directory of Open Access Journals (Sweden)

      Denise A. Valenti

      2010-01-01

      Full Text Available Imaging through the visual system in Alzheimer's disease, with the technology currently in widespread use for the diagnosis and management of eye disease such as glaucoma and macular degeneration, is proving to be promising. In vivo cross-section imaging during an annual comprehensive eye exam has been available for a decade for glaucoma and macular degeneration, and this same imaging, using Optical Coherence Tomography, has been demonstrated to show deficits specific to AD and mild cognitive impairment. These deficits are in the form of nerve fiber layer tissue drop out in the retina and optic nerve. The retrograde loss of nerve fiber layer tissue in the retina and optic nerve may be an early biomarker of AD, and these deficits in the nerve fiber layer of the retina and optic nerve may be the earliest sign of AD, even prior to damage to the hippocampal region that impacts memory.

    18. Derivation of a new ADAS-cog composite using tree-based multivariate analysis: prediction of conversion from mild cognitive impairment to Alzheimer disease.

      Science.gov (United States)

      Llano, Daniel A; Laforet, Genevieve; Devanarayan, Viswanath

      2011-01-01

      Model-based statistical approaches were used to compare the ability of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), cerebrospinal fluid (CSF), fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance imaging (MRI) markers to predict 12-month progression from mild cognitive impairment (MCI) to Alzheimer disease (AD). Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set, properties of the 11-item ADAS-cog (ADAS.11), the 13-item ADAS-cog (ADAS.All) and novel composite scores were compared, using weighting schemes derived from the Random Forests (RF) tree-based multivariate model. Weighting subscores using the RF model of ADAS.All enhanced discrimination between elderly controls, MCI and AD patients. The ability of the RF-weighted ADAS-cog composite and individual scores, along with neuroimaging or biochemical biomarkers to predict MCI to AD conversion over 12 months was also assessed. Although originally optimized to discriminate across diagnostic categories, the ADAS. All, weighted according to the RF model, did nearly as well or better than individual or composite baseline neuroimaging or CSF biomarkers in prediction of 12-month conversion from MCI to AD. These suggest that a modified subscore weighting scheme applied to the 13-item ADAS-cog is comparable to imaging or CSF markers in prediction of conversion from MCI to AD at 12 months. Copyright © 2011 by Lippincott Williams & Wilkins

    19. Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical Alzheimer's Disease.

      Science.gov (United States)

      Loewenstein, David A; Curiel, Rosie E; Duara, Ranjan; Buschke, Herman

      2018-04-01

      In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer's disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference. The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested.

    20. Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.

      Science.gov (United States)

      Mattsson, Niklas; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj

      2017-05-01

      Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.

    1. Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

      Science.gov (United States)

      Estrada, L D; Soto, C

      2007-01-01

      Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

    2. Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease.

      Science.gov (United States)

      Williams, Erik A; McGuone, Declan; Frosch, Matthew P; Hyman, Bradley T; Laver, Nora; Stemmer-Rachamimov, Anat

      2017-05-01

      Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features. We examined one or both eyes from 19 autopsy cases, 17 of which had varying degrees of AD-related changes, and 2 of which were age-matched controls. Three cases had glaucoma and 4 had macular degeneration. Immunohistochemistry for tau, β-amyloid, TDP-43, ubiquitin, and α-synuclein showed no evidence of inclusions, deposits or other protein accumulation in any case, in any part of the globe. This finding suggests that regardless of the severity of changes seen in the brain in AD, there are no similar changes in the globe. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

    3. Effects of medicinal plants on Alzheimer's disease and memory deficits

      Directory of Open Access Journals (Sweden)

      Muhammad Akram

      2017-01-01

      Full Text Available Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.

    4. 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.

    5. Semantic Memory in the Clinical Progression of Alzheimer Disease.

      Science.gov (United States)

      Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

      2017-09-01

      Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

    6. For better or worse: Immune system involvement in Alzheimer's Disease

      Directory of Open Access Journals (Sweden)

      Emma L. Walton

      2018-02-01

      Full Text Available In this issue of the Biomedical Journal, we explore the key role of the immune system in the development of Alzheimer's disease. We also learn more about the link between two disorders related to metabolic imbalances, with findings that could help to inform future screening programs. Finally, we would like to highlight some big news for our journal: the Biomedical Journal will be indexed in the Science Citation Index and receive its first official impact factor from this year. Keywords: Alzheimer's disease, Tau, Immune responses, Subclinical hypothyroidism, Metabolic disease

    7. Diffusion Tensor Imaging in Alzheimer's disease

      OpenAIRE

      Rios Lagos, Marcos; Periañez, J.A.; Hernández Tamames, J.A.; Frades, B.; Alvarez Linera, Juan; Saenz Lafourcade, C.; Lubrini, G.; Resler, G.; Frank, A.

      2011-01-01

      Attentional control and Information processing speed are central concepts in cognitive psychology and neuropsychology. Functional neuroimaging and neuropsychological assessment have depicted theoretical models considering attention as a complex and non-unitary process. One of its component processes, Attentional set-shifting ability, is commonly assessed using the Trail Making Test (TMT). Performance in the TMT decreases with increasing age in adults, Mild Cognitive Impairment (MCI) and Alzhe...

    8. 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.

    9. Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

      Directory of Open Access Journals (Sweden)

      Matej Mihelčić

      Full Text Available Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD. We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A, which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01 were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP in the non-amyloidogenic pathway

    10. Nutritional strategies in the management of Alzheimer\\'s disease: systematic review and meta-analysis

      OpenAIRE

      Shirley Steffany Muñoz Fernandez

      2016-01-01

      Alzheimer\\'s disease (AD) is one of the main causes of dependency and disability in the elderly population. A number of investigations have been seeking its prevention and/or management. In this context, it is important to highlight the role of modifiable risk factors, such as nutrition. This study aims to conduct a systematic review and subsequent meta-analysis, to assess the effect of food and/or nutrients for the management of AD at different stages. This work was steered based on the Coch...

    11. CT study in Alzheimer's disease

      Energy Technology Data Exchange (ETDEWEB)

      Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji (Tokyo Metropolitan Matsuzawa Hospital (Japan))

      1983-01-01

      Cerebral atrophy on CT was studied in 18 patients with clinically diagnosed Alzheimer's disease and in 14 healthy age-matched subjects as the control. The patients with Alzheimer's disease were divided into three groups of Stages I, II and III, according to their clinical symptoms. The study of the measurement method disclosed that the computerized measurement involving calculation of the number of pixels contained within the range of the designated CT numbers is liable to produce errors for the determination of the subarachnoid spaces and the ventricles with calcified colloid plexus. Therefore, for the present study was the method adopted, in which the subarachnoid spaces and the ventricles are measured based on the number of pixels contained in the region of interest by tracing them on the display monitor. Then, both Subarachnoid Space Volume Index (SVI) and Ventricle Volume Index (VVI) were calculated as the indices for cortical atrophy and ventricular dilatation in a slice through the level of the foramen interventriculare Monroi and other three successive ones through upper regions. Cerebral atrophy observed on CT in Alzheimer patients is attributable to Alzheimer's disease processes, rather than to physiological aging of the brain. The degree of the atrophy increases in proportion to the clinical stage, and cortical atrophy is apparent even at Stage I, whereas ventricular dilatation becomes pronounced at later stage. CT is one of effective clinical tests for the diagnosis of Alzheimer's disease.

    12. Survival of Persons with Alzheimer's Disease: Caregiver Coping Matters

      Science.gov (United States)

      McClendon, McKee J.; Smyth, Kathleen A.; Neundorfer, Marcia M.

      2004-01-01

      Purpose: Although persons with Alzheimer's disease (AD) require increasingly more assistance with activities of daily living as their disease progresses, the caregiving environment has received little attention as a source of predictors of their survival time. We report here on a study to determine whether variation in survival time of persons…

    13. Distress and Coping among Caregivers of Victims of Alzheimer's Disease.

      Science.gov (United States)

      Dundon, Margaret M.; And Others

      Alzheimer's disease is an insidious, progressively destructive brain disease which leads to the loss of judgment, communication skills, and psychomotor control preventing the victim from living independently. The consequences of caring for victims include emotional, physical, and familial strain as the caregiver is faced with the progressive…

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

      DEFF Research Database (Denmark)

      Sparre-Sørensen, Maja; Kristensen, Gustav David Westergaard

      2015-01-01

      BACKGROUND: Several studies published over the last few years have shown that malnutrition is a risk factor for developing and worsening Alzheimer's disease (AD) and that a balanced diet can delay the onset of the disease. During the period from January 1999 to January 2007, a statistically...

    15. Revising the definition of Alzheimer's disease: a new lexicon

      NARCIS (Netherlands)

      Dubois, B; Feldman, H.H.; Jacova, C.; Cummings, J.L.; Dekosky, S.T.; Barberger-Gateau, P.; Delacourte, A.; Frisoni, G.; Fox, N.C.; Galasko, D.; Gauthier, S.; Hampel, H.; Jicha, G.A.; Meguro, K.; O'Brien, J.; Pasquier, F.; Robert, P.; Rossor, M.; Salloway, S.; Sarazin, M.; de Souza, L.C.; Stern, Y.; Visser, P.J.; Scheltens, P.

      2010-01-01

      Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific

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

      Science.gov (United States)

      Sammons, Vivian O., Comp.

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

    17. 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 age-related white matter changes (ARWMC) and progression of the disease....

    18. Failure of Neuronal Maturation in Alzheimer Disease Dentate Gyrus

      Science.gov (United States)

      Li, Bin; Yamamori, Hidenaga; Tatebayashi, Yoshitaka; Shafit-Zagardo, Bridget; Tanimukai, Hitoshi; Chen, She; Iqbal, Khalid; Grundke-Iqbal, Inge

      2011-01-01

      The dentate gyrus, an important anatomic structure of the hippocampal formation, is one of the major areas in which neurogenesis takes place in the adult mammalian brain. Neurogenesis in the dentate gyrus is thought to play an important role in hippocampus-dependent learning and memory. Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased. PMID:18091557

    19. Nasal steroids as a possible treatment for Alzheimer's disease.

      Science.gov (United States)

      Lehrer, Steven; Rheinstein, Peter H

      2017-10-01

      Quite a number of experimental treatments, which are based on conventionally accepted understandings of Alzheimer's disease, have not yielded expected results. Therefore, conventionally accepted understanding of the mechanisms of the disease may be inadequate or even wrong. The characteristic amyloid plaques and tau tangles in the brain may be a result, not a cause. Alzheimer's disease is more likely the product of neuroinflammation and deranged brain wound healing. If so, a hypothesized treatment, intranasal glucocorticoids, might be effective. Long-term use of intranasal glucocorticoids (especially older generation steroids) for Alzheimer's treatment would potentially raise intraocular pressure, but newer intranasal steroids (fluticasone, triamcinolone, or budesonide) have a minimal effect on intraocular pressure because of their low bioavailability.

    20. 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 For ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going through ...