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  1. 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 ...

  2. 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 ...

  3. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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 ...

  6. 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 ...

  7. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

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    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S. (National Cancer Institute, Frederick, MD (USA))

    1988-10-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.

  8. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

    International Nuclear Information System (INIS)

    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S.

    1988-01-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease

  9. Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera.

    Directory of Open Access Journals (Sweden)

    Eric Nagele

    Full Text Available After decades of Alzheimer's disease (AD research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease.

  10. Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer's disease.

    Science.gov (United States)

    Lim, Andrew S P; Klein, Hans-Ulrich; Yu, Lei; Chibnik, Lori B; Ali, Sanam; Xu, Jishu; Bennett, David A; De Jager, Philip L

    2017-04-03

    Circadian and seasonal rhythms are seen in many species, modulate several aspects of human physiology, including brain functions such as mood and cognition, and influence many neurological and psychiatric illnesses. However, there are few data regarding the genome-scale molecular correlates underlying these rhythms, especially in the human brain. Here, we report widespread, site-specific and interrelated diurnal and seasonal rhythms of gene expression in the human brain, and show their relationship with parallel rhythms of epigenetic modification including histone acetylation, and DNA methylation. We also identify transcription factor-binding sites that may drive these effects. Further, we demonstrate that Alzheimer's disease pathology disrupts these rhythms. These data suggest that interrelated diurnal and seasonal epigenetic and transcriptional rhythms may be an important feature of human brain biology, and perhaps human biology more broadly, and that changes in such rhythms may be consequences of, or contributors to, diseases such as Alzheimer's disease.

  11. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease.

    Science.gov (United States)

    Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A

    2013-08-15

    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

  12. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    Science.gov (United States)

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Ethical issues in Alzheimer's disease research involving human subjects.

    Science.gov (United States)

    Davis, Dena S

    2017-12-01

    As we aggressively pursue research to cure and prevent Alzheimer's disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are (1) the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects' death; (2) the creation of cohorts of 'study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; (3) reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; (4) the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants' welfare if the information is obtained by insurance companies or long-term care providers; (5) the use of study partners that creates unique risks of harm to the relationship of subject and study partner. We need greater attention, at all levels, to these complex ethical issues. Work on these issues should be included in research plans, from the federal to the local, and should be supported through NIH in the same way that it supported work on the ethical, legal and social implications of genetic research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

    Science.gov (United States)

    Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2014-01-01

    In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  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

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    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

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    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. Alzheimer's Disease Facts and Figures

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    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, ...

  19. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid.

    Directory of Open Access Journals (Sweden)

    Ronald C Hendrickson

    Full Text Available Disease modifying treatments for Alzheimer's disease (AD constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001 and SME-2 (p = 0.0004 for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR, in AD were 21% (p = 0.039 and 17% (p = 0.026 lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic.

  20. 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)

  1. 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....

  2. Conantokin probes of NMDA receptors in normal and Alzheimer disease human cerebral cortex

    International Nuclear Information System (INIS)

    Ragnarsson, L.; Dodd, P.R.; Lewis, R.J.

    2002-01-01

    Full text: The pharmacology of the N-methyl-D-aspartate (NMDA) receptor site was examined in pathologically affected and relatively spared regions of cerebral cortex tissue obtained at autopsy from Alzheimer disease cases and matched controls. The affinity and density of the [ 3 H]MK-801 binding site were delineated along with the enhancement of [ 3 H]MK-801 binding by glutamate and spermine. Sites with distinct pharmacologies were distributed regionally through the cortex. The differences could not be explained by variations in the parameters of [ 3 H]MK-801 binding; rather, the data suggest that the subunit composition of NMDA receptors may be locally variable. Selective differences were also found between controls and Alzheimer disease cases in certain brain regions. The interactions of human NMDA sites with the Ala(7) and Lys(7) derivatives of conantokin-G (Con-G) were also characterized. Ala(7)-con-G showed the higher affinity of the two peptides, and also defined two distinct binding sites in controls. In distinction to the Ala(7) peptide, Lys(7)- con-G showed preferential binding to receptor sites in Alzheimer disease cf. control brain. Modified conantokins are useful for identifying differences in subunit composition of the NMDA receptors between brain areas. They may also have potential as protective agents against over-excitation mediated by specific NMDA receptors, which might contribute to localized brain damage in Alzheimer disease. For further characterization of the pharmacology of different NMDA receptor subunits, a mammalian expression system has been developed for the analysis of their responses to selected ligands, including conantokins. Copyright (2002) Australian Neuroscience Society

  3. Alzheimer's Disease Facts and Figures

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    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, ...

  4. Alzheimer's Disease Facts and Figures

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    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 ...

  5. 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 ...

  6. Alzheimer's Disease Facts and Figures

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    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 ...

  7. 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.

  8. 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.

  9. Alzheimer's Disease Facts and Figures

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    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 ...

  10. Alzheimer's Disease Facts and Figures

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    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 ...

  11. Alzheimer's Disease Facts and Figures

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    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 ...

  12. Alzheimer's Disease Facts and Figures

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    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 ...

  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. Non human primate models for Alzheimer's disease-related research and drug discovery

    NARCIS (Netherlands)

    Van Dam, Debby; De Deyn, Peter Paul

    2017-01-01

    Introduction: Pathophysiological mechanisms underlying Alzheimer's disease (AD) remain insufficiently documented for the identification of accurate diagnostic markers and purposeful target discovery and development. Nonhuman primates (NHPs) have important translational value given their close

  16. 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...

  17. Alzheimer's Disease Facts and Figures

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    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 ...

  18. Alzheimer's Disease Facts and Figures

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    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 ...

  19. Alzheimer's Disease Facts and Figures

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    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 ...

  20. 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 ...

  1. 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 ...

  2. 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, ...

  3. 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 ...

  4. Cerebral blood flow reduction in Alzheimer's disease: impact of capillary occlusions on mice and humans

    Science.gov (United States)

    Berg, Maxime; Merlo, Adlan; Peyrounette, Myriam; Doyeux, Vincent; Smith, Amy; Cruz-Hernandez, Jean; Bracko, Oliver; Haft-Javaherian, Mohammad; Nishimura, Nozomi; Schaffer, Chris B.; Davit, Yohan; Quintard, Michel; Lorthois, Sylvie

    2017-11-01

    Alzheimer's disease may be the most common form of dementia, yet a satisfactory diagnosis procedure has still to be found. Recent studies suggest that a significant decrease of cerebral blood flow, probably caused by white blood cells stalling small vessels, may be among the earliest biological markers. To assess this hypothesis we derive a blood flow model, validate it against in vitro controlled experiments and in vivo measurements made on mice. We then investigate the influence of capillary occlusions on regional perfusion (sum of all arteriole flowrates feeding the network) of large mice and humans anatomical networks. Consistent with experiments, we observe no threshold effect, so that even a small percentage of occlusions (2-4%) leads to significant blood flow decrease (5-12%). We show that both species share the same linear dependance, suggesting possible translation from mice to human. ERC BrainMicroFlow GA61510, CALMIP HPC (Grant 2017-1541).

  5. 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 ...

  6. 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.

  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. Human Development in the Context of Aging and Chronic Illness: The Role of Attachment in Alzheimer's Disease and Stroke.

    Science.gov (United States)

    Wright, Lore K.; And Others

    1995-01-01

    Examines two illness trajectories, Alzheimer's disease and stroke, to illustrate emerging changes in human development over each course of illness and the increasing importance of attachment behavior among ill elders and their family members. Argues that attachment links ailing older people to their environment, and that attachment is vital if…

  10. Global quantitative analysis of the human brain proteome in Alzheimer's and Parkinson's Disease

    Science.gov (United States)

    Ping, Lingyan; Duong, Duc M.; Yin, Luming; Gearing, Marla; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.

    2018-03-01

    Patients with Alzheimer's disease (AD) and Parkinson's disease (PD) often have overlap in clinical presentation and brain neuropathology suggesting that these two diseases share common underlying mechanisms. Currently, the molecular pathways linking AD and PD are incompletely understood. Utilizing Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11 840 protein groups representing 10 230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra- and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of disease-specific protein signatures and molecular pathways that are common in AD and PD.

  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. Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Brew Bruce J

    2009-12-01

    Full Text Available Abstract The excitotoxin quinolinic acid (QUIN is synthesized through the kynurenine pathway (KP by activated monocyte lineage cells. QUIN is likely to play a role in the pathogenesis of several major neuroinflammatory diseases including Alzheimer's disease (AD. The presence of reactive astrocytes, astrogliosis, increased oxidative stress and inflammatory cytokines are important pathological hallmarks of AD. We assessed the stimulatory effects of QUIN at low physiological to high excitotoxic concentrations in comparison with the cytokines commonly associated with AD including IFN-γ and TNF-α on primary human astrocytes. We found that QUIN induces IL-1β expression, a key mediator in AD pathogenesis, in human astrocytes. We also explored the effect of QUIN on astrocyte morphology and functions. At low concentrations, QUIN treatment induced concomitantly a marked increase in glial fibrillary acid protein levels and reduction in vimentin levels compared to controls; features consistent with astrogliosis. At pathophysiological concentrations QUIN induced a switch between structural protein expressions in a dose dependent manner, increasing VIM and concomitantly decreasing GFAP expression. Glutamine synthetase (GS activity was used as a functional metabolic test for astrocytes. We found a significant dose-dependent reduction in GS activity following QUIN treatment. All together, this study showed that QUIN is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.

  1. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

  2. [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.

  3. 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

  4. 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.

  5. [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.

  6. 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...

  7. Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1.

    LENUS (Irish Health Repository)

    Yu, Hoi-Tin

    2010-03-01

    FE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer\\'s disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer\\'s disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene.

  8. 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

  9. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

    Science.gov (United States)

    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

  10. 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 ...

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. A Combination Cocktail Improves Spatial Attention in a Canine Model of Human Aging and Alzheimer's disease

    Science.gov (United States)

    Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

    2014-01-01

    Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019

  16. 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.

  17. [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.

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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, ...

  3. 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…

  4. 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

  5. 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

  6. 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…

  7. 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

  8. 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 ...

  9. 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 ...

  10. [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.

  11. 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 ...

  12. 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, ...

  13. 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 ...

  14. 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.

  15. 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

  16. [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.

  17. Resilience in caregivers of persons with Alzheimer's disease: A human condition to overcome caregiver vulnerability

    Directory of Open Access Journals (Sweden)

    Bernardino Fernández-Calvo

    Full Text Available Abstract In general, the experience of providing assistance to and dealing with the complications experienced by a person with Alzheimer's disease puts caregivers in a situation of high risk, vulnerability, and stress, causing serious physical and emotional problems. However, some caregivers adopt a resilient mindset, which helps them to experience and express positive feelings as well as lower their burden in relation to the care. This positive experience occurs because caregivers perceive the process of caring as less adverse. They face the situation of care with a more positive mindset and are able to resist and maintain adaptive functioning. The objective of the present narrative literature review was to emphasize the need to develop intervention programs for caregivers based on salutogenic models of resilience, resistance, and personal growth to promote positive individual, family, and community resources.

  18. 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.

  19. 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.

  20. 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.

  1. 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.)

  2. 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.

  3. Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease*

    Science.gov (United States)

    Chan, Robin B.; Oliveira, Tiago G.; Cortes, Etty P.; Honig, Lawrence S.; Duff, Karen E.; Small, Scott A.; Wenk, Markus R.; Shui, Guanghou; Di Paolo, Gilbert

    2012-01-01

    Lipids are key regulators of brain function and have been increasingly implicated in neurodegenerative disorders including Alzheimer disease (AD). Here, a systems-based approach was employed to determine the lipidome of brain tissues affected by AD. Specifically, we used liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD (LOAD) patients, as well as the forebrain of three transgenic familial AD (FAD) mouse models. Although the cerebellum lacked major alterations in lipid composition, we found an elevation of a signaling pool of diacylglycerol as well as sphingolipids in the prefrontal cortex of AD patients. Furthermore, the diseased entorhinal cortex showed specific enrichment of lysobisphosphatidic acid, sphingomyelin, the ganglioside GM3, and cholesterol esters, all of which suggest common pathogenic mechanisms associated with endolysosomal storage disorders. Importantly, a significant increase in cholesterol esters and GM3 was recapitulated in the transgenic FAD models, suggesting that these mice are relevant tools to study aberrant lipid metabolism of endolysosomal dysfunction associated with AD. Finally, genetic ablation of phospholipase D2, which rescues the synaptic and behavioral deficits of an FAD mouse model, fully normalizes GM3 levels. These data thus unmask a cross-talk between the metabolism of phosphatidic acid, the product of phospholipase D2, and gangliosides, and point to a central role of ganglioside anomalies in AD pathogenesis. Overall, our study highlights the hypothesis generating potential of lipidomics and identifies novel region-specific lipid anomalies potentially linked to AD pathogenesis. PMID:22134919

  4. LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jose F Abisambra

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a chronic neurodegenerative disorder and the most common form of dementia. The major molecular risk factor for late-onset AD is expression of the epsilon-4 allele of apolipoprotein E (apoE, the major cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR has the highest affinity for apoE and plays an important role in brain cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR and western blotting techniques we found that over-expression of APP caused increases in both LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to H4 controls. Furthermore, immunohistochemical experiments showed aberrant localization of LDLR in H4-APP neuroglioma cells, Abeta-treated primary neurons, and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent staining of LDLR and of gamma- and alpha-tubulin showed a change in LDLR localization preferentially away from the plasma membrane that was paralleled by and likely the result of a disruption of the microtubule-organizing center and associated microtubule network. CONCLUSIONS/SIGNIFICANCE: These data suggest that increased APP expression and Abeta exposure alters microtubule function, leading to reduced transport of LDLR to the plasma membrane. Consequent deleterious effects on apoE uptake and function will have implications for AD pathogenesis and/or progression.

  5. 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

  6. 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…

  7. 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

  8. 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 ...

  9. 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…

  10. 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 ...

  11. 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

  12. 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...

  13. 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)

  14. 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.

  15. 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.

  16. [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.

  17. 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

  18. Characterizing the human hippocampus in aging and Alzheimer's disease using a computational atlas derived from ex vivo MRI and histology.

    Science.gov (United States)

    Adler, Daniel H; Wisse, Laura E M; Ittyerah, Ranjit; Pluta, John B; Ding, Song-Lin; Xie, Long; Wang, Jiancong; Kadivar, Salmon; Robinson, John L; Schuck, Theresa; Trojanowski, John Q; Grossman, Murray; Detre, John A; Elliott, Mark A; Toledo, Jon B; Liu, Weixia; Pickup, Stephen; Miller, Michael I; Das, Sandhitsu R; Wolk, David A; Yushkevich, Paul A

    2018-04-17

    Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm 3 ) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.

  19. 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.

  20. 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 ...

  1. 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.

  2. 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 ...

  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 Eighty-three percent of ... 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 ... 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 ...

  5. 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.

  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. Why industry propaganda and political interference cannot disguise the inevitable role played by human exposure to aluminum in neurodegenerative diseases, including Alzheimer's disease.

    Science.gov (United States)

    Exley, Christopher

    2014-01-01

    In the aluminum age, it is clearly unpalatable for aluminum, the globe's most successful metal, to be implicated in human disease. It is unpalatable because for approximately 100 years human beings have reaped the rewards of the most abundant metal of the Earth's crust without seriously considering the potential consequences for human health. The aluminum industry is a pillar of the developed and developing world and irrespective of the tyranny of human exposure to aluminum it cannot be challenged without significant consequences for businesses, economies, and governments. However, no matter how deep the dependency or unthinkable the withdrawal, science continues to document, if not too slowly, a burgeoning body burden of aluminum in human beings. Herein, I will make the case that it is inevitable both today and in the future that an individual's exposure to aluminum is impacting upon their health and is already contributing to, if not causing, chronic diseases such as Alzheimer's disease. This is the logical, if uncomfortable, consequence of living in the aluminum age.

  8. 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.

  9. Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

    Science.gov (United States)

    Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2018-02-21

    Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  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. Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder.

    Science.gov (United States)

    Xu, Jingshu; Begley, Paul; Church, Stephanie J; Patassini, Stefano; Hollywood, Katherine A; Jüllig, Mia; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Multifunctional Effect of Human Serum Albumin Reduces Alzheimer's Disease Related Pathologies in the 3xTg Mouse Model.

    Science.gov (United States)

    Ezra, Assaf; Rabinovich-Nikitin, Inna; Rabinovich-Toidman, Polina; Solomon, Beka

    2016-01-01

    Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifests simultaneously, eventually leading to cognitive impairment and death. No treatment is currently available; however, an agent addressing several key pathologies simultaneously has a better therapeutic potential. Human serum albumin (HSA) is a highly versatile protein, harboring multifunctional properties that are relevant to key pathologies underlying AD. This study provides insight into the mechanism for HSA's therapeutic effect. In vivo, a myriad of beneficial effects were observed by pumps infusing HSA intracerebroventricularly, for the first time in an AD 3xTg mice model. A significant effect on amyloid-β (Aβ) pathology was observed. Aβ1-42, soluble oligomers, and total plaque area were reduced. Neuroblastoma SHSY5Y cell line confirmed that the reduction in Aβ1-42 toxicity was due to direct binding rather than other properties of HSA. Total and hyperphosphorylated tau were reduced along with an increase in tubulin, suggesting increased microtubule stability. HSA treatment also reduced brain inflammation, affecting both astrocytes and microglia markers. Finally, evidence for blood-brain barrier and myelin integrity repair was observed. These multidimensional beneficial effects of intracranial administrated HSA, together or individually, contributed to an improvement in cognitive tests, suggesting a non-immune or Aβ efflux dependent means for treating AD.

  13. Convolvulus pluricaulis (Shankhapushpi) ameliorates human microtubule-associated protein tau (hMAPτ) induced neurotoxicity in Alzheimer's disease Drosophila model.

    Science.gov (United States)

    Kizhakke P, Anupama; Olakkaran, Shilpa; Antony, Anet; Tilagul K, Siddanna; Hunasanahally P, Gurushankara

    2017-10-16

    Convolvulus pluricaulis (Shankhapushpi) has long been used as traditional herbal medicine in India as nerve tonic. We studied the neuroprotective effects of C. pluricaulis extract (aqueous) against human microtubule-associated protein tau (hMAPτ) induced neurotoxicity in Alzheimer's disease (AD) Drosophila model. We analysed the lifespan, locomotor activity, τ protein level, reactive oxygen species (ROS), lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in 10 th , 20 th and 30 th days old control (wild type), τ control tauopathy Drosophila reared on C. pluricaulis supplemented with regular food or regular standard food. C. pluricaulis significantly offsets hMAPτ induced early death and extends the lifespan and diminishes the level of τ protein in tauopathy Drosophila. C. pluricaulis also enhances the antioxidant enzyme activities and ameliorates the τ-induced oxidative stress and restore the depleted AChE activity in the fly model. This study provides the first evidence that supplementation of C. pluricaulis along with the regular standard food ameliorate the neurotoxic effect of hMAPτ in AD Drosophila model and also reveals that it is a potent neuroprotective agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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.

  16. 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.

  17. 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 ...

  18. 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.

  19. 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

  20. Human Induced Pluripotent stem cells and their derivatives for disease modeling and therapeutic applications in Alzheimer's disease

    DEFF Research Database (Denmark)

    Pires, C.; Hall, V.; Freude, K. K.

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) have recently been generated for various inherited diseases. These hiPSC have the capacity to differentiate into any given cell type withthe help of small compounds and growth factors aiding the process. In Alzheimer’s disease (AD) several specific...... neural subpopulations in the brain are more susceptible to degeneration and apoptosis and hiPSCs can be used in order to generate these subpopulations in cell culture dishes via directed differentiation. Subsequently these cells can be used to optimize small compound screens to identify novel drug...

  1. GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus.

    Science.gov (United States)

    Kwakowsky, Andrea; Calvo-Flores Guzmán, Beatriz; Pandya, Madhavi; Turner, Clinton; Waldvogel, Henry J; Faull, Richard L

    2018-02-27

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA type A receptors (GABA A Rs) are severely affected in Alzheimer's disease (AD). However, the distribution and subunit composition of GABA A Rs in the AD brain are not well understood. This is the first comprehensive study to show brain region- and cell layer-specific alterations in the expression of the GABA A R subunits α1-3, α5, β1-3 and γ2 in the human AD hippocampus, entorhinal cortex and superior temporal gyrus (STG). In late-stage AD tissue samples using immunohistochemistry we found significant alteration of all investigated GABA A Rs subunits except for α3 and β1 that were well preserved. The most prominent changes include an increase in GABA A R α1 expression associated with AD in all layers of the CA3 region, in the stratum (str.) granulare and hilus of the dentate gyrus (DG). We found a significant increase in GABA A R α2 expression in the str. oriens of the CA1-3, str. radiatum of the CA2,3 and decrease in the str. pyramidale of the CA1 region in AD cases. In AD there was a significant increase in GABA A R α5 subunit expression in str. pyramidale, str. oriens of the CA1 region and decrease in the STG. We also found a significant decrease in the GABA A R β3 subunit immunoreactivity in the str. oriens of the CA2, str. granulare and str. moleculare of the DG. In conclusion, these findings indicate that the expression of the GABA A R subunits shows brain region- and layer-specific alterations in AD, and these changes could significantly influence and alter GABA A R function in the disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Alzheimer's disease in the human eye. Clinical tests that identify ocular and visual information processing deficit as biomarkers.

    Science.gov (United States)

    Chang, Lily Y L; Lowe, Jennifer; Ardiles, Alvaro; Lim, Julie; Grey, Angus C; Robertson, Ken; Danesh-Meyer, Helen; Palacios, Adrian G; Acosta, Monica L

    2014-03-01

    Alzheimer's disease (AD) is the most common form of dementia with progressive deterioration of memory and cognition. Complaints related to vision are common among AD patients. Several changes in the retina, lens, and in the vasculature have been noted in the AD eye that may be the cause of visual symptoms experienced by the AD patient. Anatomical changes have been detected within the eye before signs of cognitive impairment and memory loss are apparent. Unlike the brain, the eye is a unique organ that can be visualized noninvasively at the cellular level because of its transparent nature, which allows for inexpensive testing of biomarkers in a clinical setting. In this review, we have searched for candidate biomarkers that could enable diagnosis of AD, covering ocular neurodegeneration associated with functional tests. We explore the evidence that suggests that inexpensive, noninvasive clinical tests could be used to detect AD ocular biomarkers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  12. 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, ...

  13. 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 ...

  14. 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 ...

  15. 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 & ...

  16. 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 ...

  17. 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 ...

  18. 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: ...

  19. 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. ...

  20. 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.

  1. [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.

  2. 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

  3. 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 ...

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Dementia and Humane Eldercare: A History of Dementia Care in the Age of Alzheimer's Disease

    Science.gov (United States)

    McKenzie, Mark

    2004-01-01

    The stages of life are now many, each having its own boundaries, logic, and a prescribed perspective of appropriate relations amongst and between members of the many stages. Just as there is a developing curriculum for the young, there is a developing curriculum in the area of elder care. Within the paradigm of staged human development, the end…

  9. 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...

  10. 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.

  11. 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

  12. 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.  

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. New immunoassay for the mapping of neurofibrillary degeneration in Alzheimer's disease using two monoclonal antibodies against human paired helical filament tau proteins.

    Science.gov (United States)

    Condamines, O; Buée-Scherrer, V; Boissier, L; Wattez, A; Delacourte, A; Pau, B; Mourton-Gilles, C

    1995-06-09

    Monoclonal antibodies against human paired helical filament tau (PHF-tau) proteins were produced. Two of these antibodies, AD1 and AD2, were shown by immunoblot to be directed against distinct hyperphosphorylated epitopes of the PHF-tau proteins. Using AD1 and AD2, an antigen-capture ELISA specific for PHF-tau proteins was developed and used to map the neurofibrillary degeneration of several Broadmann areas from an Alzheimer's disease patient. The results confirm that the neurofibrillary degeneration predominates in parietal and temporal lobes.

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. Alzheimer's Disease Facts and Figures

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    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 ...

  5. 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.

  6. Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

    OpenAIRE

    Martin, Antonio; De Vivo, Giulia; Gentile, Vittorio

    2011-01-01

    Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Pa...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains.

    Science.gov (United States)

    Benseny-Cases, Núria; Klementieva, Oxana; Cotte, Marine; Ferrer, Isidre; Cladera, Josep

    2014-12-16

    Amyloid peptides are the main component of one of the characteristic pathological hallmarks of Alzheimer's disease (AD): senile plaques. According to the amyloid cascade hypothesis, amyloid peptides may play a central role in the sequence of events that leads to neurodegeneration. However, there are other factors, such as oxidative stress, that may be crucial for the development of the disease. In the present paper, we show that it is possible, by using Fourier tranform infrared (FTIR) microscopy, to co-localize amyloid deposits and lipid peroxidation in tissue slides from patients affected by Alzheimer's disease. Plaques and lipids can be analyzed in the same sample, making use of the characteristic infrared bands for peptide aggregation and lipid oxidation. The results show that, in samples from patients diagnosed with AD, the plaques and their immediate surroundings are always characterized by the presence of oxidized lipids. As for samples from non-AD individuals, those without amyloid plaques show a lower level of lipid oxidation than AD individuals. However, it is known that plaques can be detected in the brains of some non-AD individuals. Our results show that, in such cases, the lipid in the plaques and their surroundings display oxidation levels that are similar to those of tissues with no plaques. These results point to lipid oxidation as a possible key factor in the path that goes from showing the typical neurophatological hallmarks to suffering from dementia. In this process, the oxidative power of the amyloid peptide, possibly in the form of nonfibrillar aggregates, could play a central role.

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. Alzheimer's Disease Facts and Figures

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    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. ...

  20. 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 |

  1. 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 |

  2. 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 ...

  3. 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 ...

  4. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  6. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. Alzheimer's Disease Facts and Figures

    Medline Plus

    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- ...

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

    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, ...

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  15. Alzheimer's Disease Facts and Figures

    Medline Plus

    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 ...

  16. 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.

  17. 78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

    Science.gov (United States)

    2013-02-08

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Alzheimer's Disease... a draft guidance for industry entitled ``Alzheimer's Disease: Developing Drugs for the Treatment of... demonstrate efficacy in clinical trials in patients in the early stages of Alzheimer's disease that occur...

  18. "Lipid raft aging" in the human frontal cortex during nonpathological aging: gender influences and potential implications in Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Ferrer, Isidre; Marín, Raquel

    2018-03-10

    Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This "lipid raft aging" exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Evidence that a synthetic amyloid-ß oligomer-binding peptide (ABP) targets amyloid-ß deposits in transgenic mouse brain and human Alzheimer's disease brain.

    Science.gov (United States)

    Chakravarthy, Balu; Ito, Shingo; Atkinson, Trevor; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Whitfield, James

    2014-03-14

    The synthetic ~5 kDa ABP (amyloid-ß binding peptide) consists of a region of the 228 kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents Aß1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering Aß oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  20. 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...

  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 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...

  2. 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.

  3. [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.

  4. 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.

  5. Aroma and taste perceptions with Alzheimer disease and stroke.

    Science.gov (United States)

    Aliani, Michel; Udenigwe, Chibuike C; Girgih, Abraham T; Pownall, Trisha L; Bugera, Jacqeline L; Eskin, Michael N A

    2013-01-01

    Chemosensory disorders of smell or taste in humans have been attributed to various physiological and environmental factors including aging and disease conditions. Aroma and taste greatly condition our food preference, selection and, consumption; the decreased appetite in patients with known neurodegenerative diseases may lead to dietary restrictions that could negatively impact nutritional and health status. The decline in olfactory and gustatory systems in patients with Alzheimer disease and various types of stroke are described.

  6. Impaired expression of GABA transporters in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus.

    Science.gov (United States)

    Fuhrer, Tessa E; Palpagama, Thulani H; Waldvogel, Henry J; Synek, Beth J L; Turner, Clinton; Faull, Richard L; Kwakowsky, Andrea

    2017-05-20

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and plays an important role in regulating neuronal excitability. GABA reuptake from the synapse is dependent on specific transporters - mainly GAT-1, GAT-3 and BGT-1 (GATs). This study is the first to show alterations in the expression of the GATs in the Alzheimer's disease (AD) hippocampus, entorhinal cortex and superior temporal gyrus. We found a significant increase in BGT-1 expression associated with AD in all layers of the dentate gyrus, in the stratum oriens of the CA2 and CA3 and the superior temporal gyrus. In AD there was a significant decrease in GAT-1 expression in the entorhinal cortex and superior temporal gyrus. We also found a significant decrease in GAT-3 immunoreactivity in the stratum pyramidale of the CA1 and CA3, the subiculum and entorhinal cortex. These observations indicate that the expression of the GATs shows brain-region- and layer-specific alterations in AD, suggesting a complex activation pattern of different GATs during the course of the disease. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. 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...

  8. 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

  9. 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

  10. 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

  11. 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 ...

  12. 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

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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...

  4. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

    Science.gov (United States)

    Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

    2016-06-15

    Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall.

  5. Metallothionein-I and -III expression in animal models of Alzheimer disease

    DEFF Research Database (Denmark)

    Carrasco, J; Adlard, P; Cotman, C

    2006-01-01

    Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human...

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. 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 ...

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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...

  17. 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

  18. 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...

  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...

  20. 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

  1. 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

  2. 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...

  3. 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 ...

  4. 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

  5. 75 FR 3243 - NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline; Notice

    Science.gov (United States)

    2010-01-20

    ... time from diagnosis to death with Alzheimer's ranges from as little as 3 years to 10 or more, depending... HUMAN SERVICES National Institutes of Health NIH State-of-the-Science Conference: Preventing Alzheimer's... the ``NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline'' to...

  6. Kinetic Modeling of the Tau PET Tracer18F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

    Science.gov (United States)

    Barret, Olivier; Alagille, David; Sanabria, Sandra; Comley, Robert A; Weimer, Robby M; Borroni, Edilio; Mintun, Mark; Seneca, Nicholas; Papin, Caroline; Morley, Thomas; Marek, Ken; Seibyl, John P; Tamagnan, Gilles D; Jennings, Danna

    2017-07-01

    18 F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate 18 F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods: 18 F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BP ND ), and SUVR. BP ND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased 18 F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R 2 > 0.93 was found between BP ND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although 18 F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BP ND , whereas SUVR sensitivity to regional cerebral blood changes needs further investigation. © 2017 by the Society of Nuclear Medicine and

  7. Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Martin

    2011-01-01

    Full Text Available Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Parkinson's disease, supranuclear palsy, Huntington's disease, and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This paper focuses on the possible molecular mechanisms by which transglutaminase activity could be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases, and on the possible therapeutic effects of selective transglutaminase inhibitors for the cure of patients with diseases characterized by aberrant transglutaminase activity.

  8. Alzheimer's disease due to loss of function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

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

  9. HuCNS-SC Human NSCs Fail to Differentiate, Form Ectopic Clusters, and Provide No Cognitive Benefits in a Transgenic Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Samuel E. Marsh

    2017-02-01

    Full Text Available Transplantation of neural stem cells (NSCs can improve cognition in animal models of Alzheimer's disease (AD. However, AD is a protracted disorder, and prior studies have examined only short-term effects. We therefore used an immune-deficient model of AD (Rag-5xfAD mice to examine long-term transplantation of human NSCs (StemCells Inc.; HuCNS-SCs. Five months after transplantation, HuCNS-SCs had engrafted and migrated throughout the hippocampus and exhibited no differences in survival or migration in response to β-amyloid pathology. Despite robust engraftment, HuCNS-SCs failed to terminally differentiate and over a quarter of the animals exhibited ectopic human cell clusters within the lateral ventricle. Unlike prior short-term experiments with research-grade HuCNS-SCs, we also found no evidence of improved cognition, no changes in brain-derived neurotrophic factor, and no increase in synaptic density. These data, while disappointing, reinforce the notion that individual human NSC lines need to be carefully assessed for efficacy and safety in appropriate long-term models.

  10. 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.

  11. [Are language disorders in Alzheimer's disease simply aphasia?

    Science.gov (United States)

    Hazif-Thomas, Cyril; Thomas, Philippe

    Alzheimer's disease is accompanied by gradual aphasia, becoming more severe when the cognitive disorders are more marked. However, the quality of care provided to the patient can modulate the evolution of these language difficulties. Aphasia is linked to a human communication deficiency and can be limited by taking into account the phatic function of language to keep the channels of communication open. Copyright © 2017. Published by Elsevier Masson SAS.

  12. 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.

  13. 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 ...

  14. 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 ...

  15. Dogs with cognitive dysfunction as a spontaneous model for early Alzheimer's Disease

    DEFF Research Database (Denmark)

    Schütt, Trine; Helboe, Lone; Pedersen, Lars Østergaard

    2016-01-01

    Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study...

  16. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology

    NARCIS (Netherlands)

    Hestiantoro, Andon; Swaab, Dick F.

    2004-01-01

    The expression of estrogen receptor (ER)alpha and -beta in the infundibular nucleus of the hypothalamus was studied immunocytochemically in 28 control subjects and 14 patients with Alzheimer's disease (AD). A shift was found from more nuclear staining of ERalpha in young female controls to more

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. 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

  4. [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.

  5. 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.

  6. Nutritional patterns associated with the maintenance of neurocognitive functions and the risk of dementia and Alzheimer's disease: A focus on human studies.

    Science.gov (United States)

    Pistollato, Francesca; Iglesias, Ruben Calderón; Ruiz, Roberto; Aparicio, Silvia; Crespo, Jorge; Lopez, Luis Dzul; Manna, Piera Pia; Giampieri, Francesca; Battino, Maurizio

    2018-03-16

    Ample epidemiological evidence suggests a strong correlation among diet, lifestyle factors and the onset and consolidation of dementia and Alzheimer's disease (AD). It has been demonstrated that AD, diabetes, obesity, insulin resistance, and cardiovascular disease are strongly interconnected pathologies. Preventive strategies and nutritional interventions seem to be promising approaches to delay neurocognitive decline and reduce the risk of AD and other non-psychiatric co-morbidities. In this regard, healthy dietary patterns, characterized by high intake of plant-based foods, probiotics, antioxidants, soy beans, nuts, and omega-3 polyunsaturated fatty acids, and a low intake of saturated fats, animal-derived proteins, and refined sugars, have been shown to decrease the risk of neurocognitive impairments and eventually the onset of AD. Here we review the role of some nutrients and, in particular, of healthy dietary patterns, such as the Mediterranean diet and other emerging healthy diets, DASH (Dietary Approach to Stop Hypertension) and MIND (Mediterranean-DASH dietIntervention for Neurodegenerative Delay), for the maintenance of cognitive performance, focusing specifically on human studies. The beneficial effects associated with overall diet composition, rather than single nutrient supplementations, for the prevention or the delay of AD and dementia are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qiongshi Lu

    2017-07-01

    Full Text Available Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD. Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  8. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Science.gov (United States)

    Lu, Qiongshi; Powles, Ryan L; Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

    2017-07-01

    Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  9. 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.

  10. 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....

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. 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

  16. Environment, epigenetics and neurodegeneration: Focus on nutrition in Alzheimer's disease.

    Science.gov (United States)

    Nicolia, Vincenzina; Lucarelli, Marco; Fuso, Andrea

    2015-08-01

    Many different environmental factors (nutrients, pollutants, chemicals, physical activity, lifestyle, physical and mental stress) can modulate epigenetic markers in the developing and adult organism. Epigenetics, in turn, can cause and is associated with several neurodegenerative and aging-dependent human diseases. Alzheimer's disease certainly represents one of the most relevant neurodegenerative disorders due to its incidence and its huge socio-economic impact. Therefore, it is easy to understand why recent literature focuses on the epigenetic modifications associated with Alzheimer's disease and other neurodegenerative disorders. One of the most intriguing and, at the same time, worrying evidence is that even "mild" environmental factors (such as behavioral or physical stress) as well as the under-threshold exposure to pollutants and chemicals, can be effective. Finally, even mild nutrients disequilibria can result in long-lasting and functional alterations of many epigenetic markers, although they don't have an immediate acute effect. Therefore, we will probably have to re-define the current risk threshold for many factors, molecules and stresses. Among the many different environmental factors affecting the epigenome, nutrition represents one of the most investigated fields; the reasons are probably that each person interacts with nutrients and that, in turn, nutrients can modulate at molecular level the epigenetic biochemical pathways. The role that nutrition can exert in modulating epigenetic modifications in Alzheimer's disease will be discussed with particular emphasis on the role of B vitamins and DNA methylation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Olive Oil and its Potential Effects on Alzheimer's Disease

    Science.gov (United States)

    Antony, Shan; Zhang, G. P.

    Alzheimer's disease is a neuro-degenerative brain disease that is responsible for affecting the lives of hundreds of thousands of people every year. There has been no evidence to suggest a cure for the disease and the only existing treatments have very low rates of success in trial patients. This is largely due to the fact that the brain is one of the most undiscovered parts of the human body. Brain chemistry is highly complex and responds to its environment in random and radical ways. My research includes testing the reactionary outcomes of combining compounds of olive oil with the 20 basic amino acids. Regions around the world with olive oil based diets show a direct correlation to lower rates of Alzheimer's. Testing few compounds of olive oil with chemicals already found in the brain may yield to a better understanding as to why that is. I took the compounds tyrosol, hydroxytyrosol, and oleocanthal, and combined them with the 20 basic amino acids and calculated the total energy of the new molecule. The molecules produced with acceptably low energy values will be the center of further research. These molecules could lead to truly understanding olive oil's effect on the brain, and ultimately, the cure or prevention of Alzheimer's disease.

  18. 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.

  19. 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.

  20. [Learning and memory amelioration of transplantation of the neural stem cells modified with human brain-derived neurotrophic factor gene on Alzheimer disease model rat].

    Science.gov (United States)

    Zhao, Zhiying; Hu, Haitao; Feng, Gaifeng

    2005-05-01

    To investigate the memory amelioration of the Alzheimer disease (AD) model rat after being transplanted the single neural stem cells (NSC) and NSC modified with human brain-derived neurotrophic factor (hBDNF) gene. Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group III and group IV respectively. Two weeks after transplantation, the amelioration of memory impairment of the rats was detected by Morris water maze. The average escaping latency of the group III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter than that of the group II (70.91 +/- 23.67 s) (P0.05). More lineal and oriented strategies were used in group IV. The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the group III.

  1. Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

    Directory of Open Access Journals (Sweden)

    Petr Ponomarenko

    2017-07-01

    Full Text Available While year after year, conditions, quality, and duration of human lives have been improving due to the progress in science, technology, education, and medicine, only eight diseases have been increasing in prevalence and shortening human lives because of premature deaths according to the retrospective official review on the state of US health, 1990-2010. These diseases are kidney cancer, chronic kidney diseases, liver cancer, diabetes, drug addiction, poisoning cases, consequences of falls, and Alzheimer's disease (AD as one of the leading pathologies. There are familial AD of hereditary nature (~4% of cases and sporadic AD of unclear etiology (remaining ~96% of cases; i.e., non-familial AD. Therefore, sporadic AD is no longer a purely medical problem, but rather a social challenge when someone asks oneself: “What can I do in my own adulthood to reduce the risk of sporadic AD at my old age to save the years of my lifespan from the destruction caused by it?” Here, we combine two computational approaches for regulatory SNPs: Web service SNP_TATA_Comparator for sequence analysis and a PubMed-based keyword search for articles on the biochemical markers of diseases. Our purpose was to try to find answers to the question: “What can be done in adulthood to reduce the risk of sporadic AD in old age to prevent the lifespan reduction caused by it?” As a result, we found 89 candidate SNP markers of familial and sporadic AD (e.g., rs562962093 is associated with sporadic AD in the elderly as a complication of stroke in adulthood, where natural marine diets can reduce risks of both diseases in case of the minor allele of this SNP. In addition, rs768454929, and rs761695685 correlate with sporadic AD as a comorbidity of short stature, where maximizing stature in childhood and adolescence as an integral indicator of health can minimize (or even eliminate the risk of sporadic AD in the elderly. After validation by clinical protocols, these candidate SNP

  2. 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

  3. [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.

  4. Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer's disease and neuronal loss.

    Science.gov (United States)

    Ager, Rahasson R; Davis, Joy L; Agazaryan, Andy; Benavente, Francisca; Poon, Wayne W; LaFerla, Frank M; Blurton-Jones, Mathew

    2015-07-01

    Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder, affecting over 35 million people worldwide. Pathologically, AD is characterized by the progressive accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles within the brain. Together, these pathologies lead to marked neuronal and synaptic loss and corresponding impairments in cognition. Current treatments, and recent clinical trials, have failed to modify the clinical course of AD; thus, the development of novel and innovative therapies is urgently needed. Over the last decade, the potential use of stem cells to treat cognitive impairment has received growing attention. Specifically, neural stem cell transplantation as a treatment for AD offers a novel approach with tremendous therapeutic potential. We previously reported that intrahippocampal transplantation of murine neural stem cells (mNSCs) can enhance synaptogenesis and improve cognition in 3xTg-AD mice and the CaM/Tet-DT(A) model of hippocampal neuronal loss. These promising findings prompted us to examine a human neural stem cell population, HuCNS-SC, which has already been clinically tested for other neurodegenerative disorders. In this study, we provide the first evidence that transplantation of research grade HuCNS-SCs can improve cognition in two complementary models of neurodegeneration. We also demonstrate that HuCNS-SC cells can migrate and differentiate into immature neurons and glia and significantly increase synaptic and growth-associated markers in both 3xTg-AD and CaM/Tet-DTA mice. Interestingly, improvements in aged 3xTg-AD mice were not associated with altered Aβ or tau pathology. Rather, our findings suggest that human NSC transplantation improves cognition by enhancing endogenous synaptogenesis. Taken together, our data provide the first preclinical evidence that human NSC transplantation could be a safe and effective therapeutic approach for treating AD. © 2014 The Authors. Hippocampus

  5. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study.

    Science.gov (United States)

    Steele, Natasha Z R; Carr, Jessie S; Bonham, Luke W; Geier, Ethan G; Damotte, Vincent; Miller, Zachary A; Desikan, Rahul S; Boehme, Kevin L; Mukherjee, Shubhabrata; Crane, Paul K; Kauwe, John S K; Kramer, Joel H; Miller, Bruce L; Coppola, Giovanni; Hollenbach, Jill A; Huang, Yadong; Yokoyama, Jennifer S

    2017-03-01

    Alzheimer disease (AD) is a progressive disorder that affects cognitive function. There is increasing support for the role of neuroinflammation and aberrant immune regulation in the pathophysiology of AD. The immunoregulatory human leukocyte antigen (HLA) complex has been linked to susceptibility for a number of neurodegenerative diseases, including AD; however, studies to date have failed to consistently identify a risk HLA haplotype for AD. Contributing to this difficulty are the complex genetic organization of the HLA region, differences in sequencing and allelic imputation methods, and diversity across ethnic populations. Building on prior work linking the HLA to AD, we used a robust imputation method on two separate case-control cohorts to examine the relationship between HLA haplotypes and AD risk in 309 individuals (191 AD, 118 cognitively normal [CN] controls) from the San Francisco-based University of California, San Francisco (UCSF) Memory and Aging Center (collected between 1999-2015) and 11,381 individuals (5,728 AD, 5,653 CN controls) from the Alzheimer's Disease Genetics Consortium (ADGC), a National Institute on Aging (NIA)-funded national data repository (reflecting samples collected between 1984-2012). We also examined cerebrospinal fluid (CSF) biomarker measures for patients seen between 2005-2007 and longitudinal cognitive data from the Alzheimer's Disease Neuroimaging Initiative (n = 346, mean follow-up 3.15 ± 2.04 y in AD individuals) to assess the clinical relevance of identified risk haplotypes. The strongest association with AD risk occurred with major histocompatibility complex (MHC) haplotype A*03:01~B*07:02~DRB1*15:01~DQA1*01:02~DQB1*06:02 (p = 9.6 x 10-4, odds ratio [OR] [95% confidence interval] = 1.21 [1.08-1.37]) in the combined UCSF + ADGC cohort. Secondary analysis suggested that this effect may be driven primarily by individuals who are negative for the established AD genetic risk factor, apolipoprotein E (APOE) ɛ4. Separate

  6. 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

  7. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    of the major paradigm in the field, the amyloid hypothesis, are sharply formulated. These challenges together show that new approaches are necessary that address data heterogeneity, increase focus on the proteome level, use available human patient data more actively, account for the aging phenotype......The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...

  8. Studies on Colony Stimulating Factor Receptor-1 and Ligands Colony Stimulating Factor-1 and Interleukin-34 in Alzheimer's Disease Brains and Human Microglia

    Directory of Open Access Journals (Sweden)

    Douglas G. Walker

    2017-08-01

    Full Text Available Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115 for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1 and the more recently identified interleukin-34 (IL-34. Studies of IL-34 activation of rodent microglia and human macrophages have suggested it has different properties to CSF-1, resulting in an anti-inflammatory reparative phenotype. The goal of this study was to identify if the responses of human postmortem brain microglia to IL-34 differed from their responses to CSF-1 with the aim of identifying different phenotypes of microglia as a result of their responses. To approach this question, we also sought to identify differences between IL-34, CSF-1, and CSF-1R expression in human brain samples to establish whether there was an imbalance in Alzheimer's disease (AD. Using human brain samples [inferior temporal gyrus (ITG and middle temporal gyrus (MTG] from distinct cohorts of AD, control and high pathology, or mild cognitive impairment cases, we showed that there was increased expression of CSF-1R and CSF-1 mRNAs in both series of AD cases, and reduced expression of IL-34 mRNA in AD ITG samples. There was no change in expression of these genes in RNA from cerebellum of AD, Parkinson's disease (PD, or control cases. The results suggested an imbalance in CSF-1R signaling in AD. Using RNA sequencing to compare gene expression responses of CSF-1 and IL-34 stimulated human microglia, a profile of responses to CSF-1 and IL-34 was identified. Contrary to earlier work with rodent microglia, IL-34 induced primarily a classical activation response similar to that of CSF-1. It was not possible to identify any genes expressed significantly different by IL-34-stimulated microglia compared to CSF-1-stimulated microglia, but both cytokines did induce

  9. 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,

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. [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.

  17. Binding Patterns Associated Aß-HSP60 p458 Conjugate to HLA-DR-DRB Allele of Human in Alzheimer's Disease: An In Silico Approach.

    Science.gov (United States)

    Padmadas, Naveen; Panda, Pritam Kumar; Durairaj, Sudarsanam

    2016-04-23

    Alzheimer's disease (AD) is a complex, irreversible, progressive brain disorder, which diminishes memory in a slow pace and thinking skills; ranked third by experts. It is a complex disorder that involves numerous cellular and subcellular alterations. The pathogenesis of AD is still unknown, but for better understanding, we proposed an in silico analysis to find out the binding patterns associated with HSP60. Several experimental conclusions have been drawn to understand the actual mechanism behind the forming of aggregation due to misfolding. Protein misfolding disorder is experimentally identified by the accumulation of protein aggregates at the intracellular or extracellular region of brain that adversely affects the cell functioning by disrupting the connection between the cells and ultimately leading to cell death. To unravel the mystery behind the mechanism of AD through computational approach, the current proposal shows the designing of Aß-HSP60 p458 conjugate followed by secondary structure analysis, which is further targeted to HLA-DR-DRB allele of human. The antigenicity of Aß (1-42) peptide is the major concern in our study predicted through PVS server, which provides an insight into the immunogenic behavior of Aß peptide. The mechanism involved in the interaction of HSP60-Aß conjugate with HLA-DR-DRB allele considering the fact that Aß (1-42) is highly immunogenic in human and interactions evoked highly robust T-cell response through MHC class II binding predictions. It was assisted by molecular dynamics simulation of predicted HSP60 structure followed by validation through Ramachandran plot analysis and protein-protein interaction of Aß (1-42) with HSP60.

  18. Recombinant human NGF-loaded microspheres promote survival of basal forebrain cholinergic neurons and improve memory impairments of spatial learning in the rat model of Alzheimer's disease with fimbria-fornix lesion.

    Science.gov (United States)

    Gu, Haigang; Long, Dahong; Song, Cunxian; Li, Xiaobin

    2009-04-10

    Neurotrophic factors are used for the experimental treatment of neurological disorders, such as Alzheimer's disease. However, delivery of the neurotrophic factors into the brain remains a big challenge. Recombinant human nerve growth factor (NGF)-loaded microspheres were fabricated and characterized in vitro and in vivo in our previous study. The present study was to assess the therapeutic benefit of rhNGF-loaded microspheres in treating the rat model of Alzheimer's disease with fimbria-fornix lesion. Recombinant human NGF-loaded microspheres were implanted into the basal forebrain of the rats with fimbria-fornix lesion. Four weeks after implantation in the basal forebrain, immunohistochemical analysis showed that rhNGF-loaded microspheres had a significant effect on the survival of axotomized cholinergic neurons in the medial septum (MS) and vertical diagonal branch (VDB) (pimprove the ability of spatial learning and memory of the rats with fimbria-fornix lesion (p<0.05). These results indicate that rhNGF-loaded microspheres are an effective means for the treatment of Alzheimer's disease.

  19. 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.

  20. [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) .

  1. 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.

  2. 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.

  3. 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...

  4. 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…

  5. 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....

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

    DEFF Research Database (Denmark)

    Soininen, Hilkka; Mattila, Jussi; Koikkalainen, Juha

    2012-01-01

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

  7. 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…

  8. 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…

  9. 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.

  10. [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.

  11. 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)

  12. [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.

  13. 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.

  14. Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix-assisted laser desorption/ionization-imaging mass spectrometry.

    Science.gov (United States)

    Mendis, Lakshini H S; Grey, Angus C; Faull, Richard L M; Curtis, Maurice A

    2016-10-01

    Alzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by β-amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis-mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each hippocampal subfield (e.g., Cornu Ammonis [CA] 1-4, dentate gyrus [DG] etc.). Since each subfield has its own function, we postulated that there could be lipid changes that are unique to each. We used matrix-assisted laser desorption/ionization-imaging mass spectrometry to investigate specific lipid changes in each subfield in AD. Data from the hippocampus region of six age- and gender-matched normal and AD pairs were analyzed with SCiLS lab 2015b software (SCiLS GmbH, Germany; RRID:SCR_014426), using an analysis workflow developed in-house. Hematoxylin, eosin, and luxol fast blue staining were used to precisely delineate each anatomical hippocampal subfield. Putative lipid identities, which were consistent with published data, were assigned using MS/MS. Both positively and negatively charged lipid ion species were abundantly detected in normal and AD tissue. While the distribution pattern of lipids did not change in AD, the abundance of some lipids changed, consistent with trends that have been previously reported. However, our results indicated that the majority of these lipid changes specifically occur in the CA1 region. Additionally, there were many lipid changes that were specific to the DG. Matrix-assisted laser desorption/ionization-imaging mass spectrometry and our analysis workflow provide a novel method to investigate specific lipid changes in hippocampal subfields. Future work will focus on elucidating the role that specific lipid differences in each subfield play in AD pathogenesis.

  15. Expression of tryptophan 2,3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer's disease brain.

    Directory of Open Access Journals (Sweden)

    Wei Wu

    Full Text Available To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD, the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO, and the metabolites tryptophan, kynurenine, kynurenic acid, quinolinic acid and picolinic acid were assessed in different brain regions of triple transgenic AD mice. The expression and cell distribution of TDO and quinolinic acid, and their co-localization with neurofibrillary tangles and senile β amyloid deposition were also determined in hippocampal sections from human AD brains. The expression of TDO mRNA was significantly increased in the cerebellum of AD mouse brain. Immunohistochemistry demonstrated that the density of TDO immuno-positive cells was significantly higher in the AD mice. The production of the excitotoxin quinolinic acid strongly increased in the hippocampus in a progressive and age-dependent manner in AD mice. Significantly higher TDO and indoleamine 2,3 dioxygenase 1 immunoreactivity was observed in the hippocampus of AD patients. Furthermore, TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of AD. These results show that the kynurenine pathway is over-activated in AD mice. This is the first report demonstrating that TDO is highly expressed in the brains of AD mice and in AD patients, suggesting that TDO-mediated activation of the kynurenine pathway could be involved in neurofibrillary tangles formation and associated with senile plaque. Our study adds to the evidence that the kynurenine pathway may play important roles in the neurodegenerative processes of AD.

  16. Calcium-Sensing Receptors of Human Astrocyte-Neuron Teams: Amyloid-β-Driven Mediators and Therapeutic Targets of Alzheimer's Disease.

    Science.gov (United States)

    Dal Prà, I; Chiarini, A; Pacchiana, R; Gardenal, E; Chakravarthy, B; Whitfield, J F; Armato, U

    2014-07-01

    It is generally assumed that the neuropathology of sporadic (late-onset or nonfamilial) Alzheimer's disease (AD) is driven by the overproduction and spreading of first Amyloid-βx-42 (Aβ42) and later hyperphosphorylated (hp)-Tau oligomeric "infectious seeds". Hitherto, only neurons were held to make and spread both oligomer types; astrocytes would just remove debris. However, we have recently shown that exogenous fibrillar or soluble Aβ peptides specifically bind and activate the Ca(2+)-sensing receptors (CaSRs) of untransformed human cortical adult astrocytes and postnatal neurons cultured in vitro driving them to produce, accrue, and secrete surplus endogenous Aβ42. While the Aβ-exposed neurons start dying, astrocytes survive and keep oversecreting Aβ42, nitric oxide (NO), and vascular endothelial growth factor (VEGF)-A. Thus astrocytes help neurons' demise. Moreover, we have found that a highly selective allosteric CaSR agonist ("calcimimetic"), NPS R-568, mimics the just mentioned neurotoxic actions triggered by Aβ●CaSR signaling. Contrariwise, and most important, NPS 2143, a highly selective allosteric CaSR antagonist ("calcilytic"), fully suppresses all the Aβ●CaSR signaling-driven noxious actions. Altogether our findings suggest that the progression of AD neuropathology is promoted by unceasingly repeating cycles of accruing exogenous Aβ42 oligomers interacting with the CaSRs of swelling numbers of astrocyte-neuron teams thereby recruiting them to overrelease additional Aβ42 oligomers, VEGF-A, and NO. Calcilytics would beneficially break such Aβ/CaSR-driven vicious cycles and hence halt or at least slow the otherwise unstoppable spreading of AD neuropathology.

  17. Is immunotherapy an effective treatment for Alzheimer's disease?

    Directory of Open Access Journals (Sweden)

    Licastro Federico

    2004-11-01

    Full Text Available Abstract Immunotherapy in patients with Alzheimer's disease (AD is rapidly becoming a hot topic of modern geriatric and clinical gerontology. Current views see immunization with Aβ peptide, the amyloidogenic protein found in senile plaque of AD patient's brains, or the infusion of preformed antibody specific for human Aβ, as possible therapeutic approaches to improve the cognitive status in the disease. Animal models of the disease have provided positive results from both approaches. Thus, an initial clinical trial using immunization with human Aβ in AD patients was started, but then shortly halted because of an unusually high incidence (6% of meningoencephalitis. A long and currently ongoing debate in the scientific community about the pro or contra of vaccination or passive immunization with Aβ in AD is thereafter started. Here, the authors would like to stress few points of concern regarding these approaches in clinical practice.

  18. Preclinical MRI and NMR Bio-markers of Alzheimer's Disease: Concepts and Applications

    International Nuclear Information System (INIS)

    Dhenain, M.; Dhenain, M.; Dhenain, M.

    2008-01-01

    Alzheimer's disease is an important social and economic issue for our societies. The development of therapeutics against this severe dementia requires assessing the effects of new drugs in animal models thanks to dedicated bio-markers. This review first overviews Alzheimer's disease and its models as well as the concept of bio-markers. It then focuses on MRI and NMR bio-markers of Alzheimer's disease in animals. Anatomical markers such as atrophy and angiography are useful to phenotype newly developed models of Alzheimer's disease, even if the alterations in these animals are not as severe as in humans. Amyloid plaques imaging is a promising marker of the pathology in animals, and is a rapidly evolving field of MRI. Functional methods such as perfusion and diffusion imaging or spectroscopy are able to detect alterations in transgenic mice mimicking Alzheimer and also to show similar alterations than in humans. They can thus be good translational markers of the disease. Manganese-Enhanced MRI shows a reduction of neuronal transportation in transgenic models of Alzheimer and it allows monitoring improvements induced by treatments of the disease. It is thus a promising bio-marker of the pathology in animals. (authors)

  19. 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.

  20. 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...

  1. 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....

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease.

    Science.gov (United States)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges of the major paradigm in the field, the amyloid hypothesis, are sharply formulated. These challenges together show that new approaches are necessary that address data heterogeneity, increase focus on the proteome level, use available human patient data more actively, account for the aging phenotype as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease.

  7. 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).

  8. 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…

  9. 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

  10. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease.

    Science.gov (United States)

    Blanch, Marta; Mosquera, Jose Luis; Ansoleaga, Belén; Ferrer, Isidre; Barrachina, Marta

    2016-02-01

    Mitochondrial dysfunction is linked with the etiopathogenesis of Alzheimer disease and Parkinson disease. Mitochondria are intracellular organelles essential for cell viability and are characterized by the presence of the mitochondrial (mt)DNA. DNA methylation is a well-known epigenetic mechanism that regulates nuclear gene transcription. However, mtDNA methylation is not the subject of the same research attention. The present study shows the presence of mitochondrial 5-methylcytosine in CpG and non-CpG sites in the entorhinal cortex and substantia nigra of control human postmortem brains, using the 454 GS FLX Titanium pyrosequencer. Moreover, increased mitochondrial 5-methylcytosine levels are found in the D-loop region of mtDNA in the entorhinal cortex in brain samples with Alzheimer disease-related pathology (stages I to II and stages III to IV of Braak and Braak; n = 8) with respect to control cases. Interestingly, this region shows a dynamic pattern in the content of mitochondrial 5-methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology progression (3, 6, and 12 months of age). Finally, a loss of mitochondrial 5-methylcytosine levels in the D-loop region is found in the substantia nigra in Parkinson disease (n = 10) with respect to control cases. In summary, the present findings suggest mtDNA epigenetic modulation in human brain is vulnerable to neurodegenerative disease states. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. 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...

  5. 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.

  6. 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

  7. 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.

  8. 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...

  9. [Neuroepigenetics: Desoxyribonucleic acid methylation in Alzheimer's disease and other dementias].

    Science.gov (United States)

    Mendioroz Iriarte, Maite; Pulido Fontes, Laura; Méndez-López, Iván

    2015-05-21

    DNA methylation is an epigenetic mechanism that controls gene expression. In Alzheimer's disease (AD), global DNA hypomethylation of neurons has been described in the human cerebral cortex. Moreover, several variants in the methylation pattern of candidate genes have been identified in brain tissue when comparing AD patients and controls. Specifically, DNA methylation changes have been observed in PSEN1 and APOE, both genes previously being involved in the pathophysiology of AD. In other degenerative dementias, methylation variants have also been described in key genes, such as hypomethylation of the SNCA gene in Parkinson's disease and dementia with Lewy bodies or hypermethylation of the GRN gene promoter in frontotemporal dementia. The finding of aberrant DNA methylation patterns shared by brain tissue and peripheral blood opens the door to use those variants as epigenetic biomarkers in the diagnosis of neurodegenerative diseases. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. [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.

  11. A phase 3 trial of IV immunoglobulin for Alzheimer disease.

    Science.gov (United States)

    Relkin, Norman R; Thomas, Ronald G; Rissman, Robert A; Brewer, James B; Rafii, Michael S; van Dyck, Christopher H; Jack, Clifford R; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M; Fritsch, Sandor; Aisen, Paul S

    2017-05-02

    We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. NCT00818662. This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD. © 2017 American Academy of Neurology.

  12. 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.

  13. Why musical memory can be preserved in advanced Alzheimer's disease.

    Science.gov (United States)

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  14. Alzheimer disease and platelets: how’s that relevant

    Directory of Open Access Journals (Sweden)

    Catricala Silvia

    2012-09-01

    Full Text Available Abstract Alzheimer Disease (AD is the most common neurodegenerative disorder worldwide, and account for 60% to 70% of all cases of progressive cognitive impairment in elderly patients. At the microscopic level distinctive features of AD are neurons and synapses degeneration, together with extensive amounts of senile plaques and neurofibrillars tangles. The degenerative process probably starts 20–30 years before the clinical onset of the disease. Senile plaques are composed of a central core of amyloid β peptide, Aβ, derived from the metabolism of the larger amyloid precursor protein, APP, which is expressed not only in the brain, but even in non neuronal tissues. More than 30 years ago, some studies reported that human platelets express APP and all the enzymatic activities necessary to process this protein through the same pathways described in the brain. Since then a large number of evidence has been accumulated to suggest that platelets may be a good peripheral model to study the metabolism of APP, and the pathophysiology of the onset of AD. In this review, we will summarize the current knowledge on the involvement of platelets in Alzheimer Disease. Although platelets are generally accepted as a suitable model for AD, the current scientific interest on this model is very high, because many concepts still remain debated and controversial. At the same time, however, these still unsolved divergences mirror a difficulty to establish constant parameters to better defined the role of platelets in AD.

  15. 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...

  16. 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.

  17. Exploratory human PET study of the effectiveness of 11C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer's disease

    International Nuclear Information System (INIS)

    Ohnishi, Akihito; Senda, Michio; Yamane, Tomohiko; Mikami, Tomoko; Nishida, Hiroyuki; Nishio, Tomoyuki; Akamatsu, Go; Ikari, Yasuhiko; Kimoto, Shogo; Aita, Kazuki; Sasaki, Masahiro; Shinkawa, Hiroko; Yamamoto, Yasuji; Shukuri, Miho; Mawatari, Aya; Doi, Hisashi; Watanabe, Yasuyoshi; Onoe, Hirotaka

    2016-01-01

    Introduction: Neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD). As a biomarker of neuroinflammatory processes, we designed 11 C-labeled ketoprofen methyl ester ([ 11 C]KTP-Me) to increase the blood–brain barrier permeability of ketoprofen (KTP), a selective cyclooxygenase-1 (COX-1) inhibitor. Animal studies indicated that [ 11 C]KTP-Me enters the brain and accumulates in activated microglia of inflammatory lesions. In a first-in-human study, we reported that [ 11 C]KTP-Me is a safe positron emission tomography (PET) tracer and enters the brain; the radioactivity is washed out from normal cerebral tissue. Here we explored the efficacy of [ 11 C]KTP-Me as a diagnostic biomarker of neuroinflammatory processes in AD. Methods: [ 11 C]KTP-Me was synthesized by rapid C-[ 11 C]methylation of [ 11 C]CH 3 I and the corresponding arylacetate precursor. Nine subjects (four healthy subjects, two Pittsburgh compound-B (PiB)-positive patients with mild cognitive impairment (MCI), and three PiB-positive AD patients) underwent a dynamic brain PET scan for 70 min after injection. We evaluated differences in cortical retention and washout rate in the brain between healthy subjects and MCI/AD patients. Results: A brain distribution pattern reflecting blood flow in the early-phase image was seen in both healthy subjects and MCI/AD patients. Cortical activity gradually cleared in all groups. However, we observed no obvious difference in the washout rate between healthy subjects and MCI/AD patients or between MCI and AD patients. Conclusions: [ 11 C]KTP-Me cannot be useful as a potential diagnostic biomarker for MCI/AD. Further improvements in binding affinity and specificity, etc., are needed to be a diagnostic biomarker of neuroinflammation in AD. Advances in knowledge and implications for patient care: [ 11 C]KTP-Me is a new tracer that targets COX-1. [ 11 C]KTP-Me is expected to be a diagnostic biomarker of neuroinflammation in

  18. Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Simonsen, A.H.; McGuire, J.; Podust, V.N.

    2008-01-01

    An early and accurate diagnosis of Alzheimer's disease (AD) is required to initiate symptomatic treatment with currently approved drugs and will be of even greater importance if disease modifying compounds in development display a clinical effect. Protein profiles of human cerebrospinal fluid...

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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...

  7. 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....

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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....

  15. 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...

  16. 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

  17. Antibodies against small heat-shock proteins in Alzheimer's disease as a part of natural human immune repertoire or activation of humoral response?

    Science.gov (United States)

    Papuć, Ewa; Krupski, Witold; Kurys-Denis, Ewa; Rejdak, Konrad

    2016-04-01

    Characterization of autoantibodies specific for some disease-related proteins, would allow to better assess their role as diagnostic and prognostic markers. In the light of increasing evidence for both humoral and cellular adaptive immune responses in the pathophysiology of Alzheimer's disease (AD), and data on the increased small heat-shock proteins (sHSP) expression in this disease, it seemed justified to assess humoral response against sHSP in AD patients. The aim of the study was to check whether AD has the ability to elicit immune response against small HSP, which could also serve as disease biomarkers. IgG and IgM autoantibodies against alpha B-crystallin and anti-HSP 60 IgG autoantibodies were assessed in 59 AD patients and 59 healthy subjects. Both IgM and IgG autoantibodies against alpha B-crystallin in AD patients were significantly higher compared to healthy controls (p immune repertoire, and chronic neurodegenerative process does not have significant inducing effect on the systemic immunoreactivity against HSP60. Increased titers of IgM and IgG autoantibodies against alpha B-crystallin in AD patients may reflect activation of humoral immune response in the course of this chronic disease, probably secondary to its increased expression. Further prospective studies, on larger group of AD patients and measuring a change in antibodies titers with disease progression are necessary to assess the exact role of these antibodies in AD.

  18. 77 FR 14804 - Advisory Council on Alzheimer's Research, Care, and Services; Request for Nominations

    Science.gov (United States)

    2012-03-13

    ... programs that impact people with Alzheimer's disease and related dementias and their caregivers. The... Alzheimer's patient advocates (2), Alzheimer's caregivers (2), health care providers (2), representatives of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Advisory Council on Alzheimer's Research, Care, and...

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Mercury exposure and Alzheimer's disease in India - An imminent threat?

    Science.gov (United States)

    Chakraborty, Parthasarathi

    2017-07-01

    India is an industrial giant with one of the fastest growing major economies in the world. Primary energy consumption in India is third after China and the USA. Greater energy production brings the burden of increasing emissions of mercury (Hg). India ranks second for Hg emissions. Rising atmospheric Hg release, high Hg evasion processes, and increasing monomethylmercury (highly neurotoxin) accumulations in marine food products increase the potential for human and ecosystem Hg exposure. Hg has been identified to increase the risk of getting Alzheimer's disease (AD). There are increasing reports of AD and dementia in different age groups in India. The relationship between increasing Hg exposure and increasing neurodegenerative disorder in India is not known. This commentary points to the need for better understanding of the relationship between Hg release and AD in India, and other countries, and how to protect human health and the environment from the adverse effects of Hg. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  6. DNA double-strand breaks measured by pulsed-field gel electrophoresis in irradiated lymphocytes from normal humans and those with Alzheimer's disease

    International Nuclear Information System (INIS)

    Tobi, S.E.; Itzhaki, R.F.

    1993-01-01

    The authors previously found that radiation-induced chromosome aberrations (dicentrics) are more numerous in lymphocytes from Alzheimer's disease (AD) patients than in those from age-matched normal individuals (Tobi et al. 1990). They have examined double-strand breaks (dsb) produced by g amma - irradiation in the DNA of AD and normal lymphocytes by using pulsed-field gel electrophoresis. The percentage of DNA migrating into the gels is an indirect measure of the number of dsb; DNA content of sequential slices of the gel was assayed by direct fluorometry and the percentage migrating was dose dependent. Results show that the level of damage is similar in AD and normal lymphocytes and preliminary assays of the rate of repair suggest that the half-time is also similar, the value being > 1 h. The latter is consistent with the known rate of rejoining of chromosome fragments in interphase lymphocytes (Pantelias and Maillie 1985). (Author)

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.)

  13. 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.

  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. 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).

  16. 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.

  17. 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.

  18. 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

  19. Can Creutzfeldt-Jakob disease unravel the mysteries of Alzheimer?

    Science.gov (United States)

    Kovacs, Gabor G

    2016-09-02

    Recent studies on iatrogenic Creutzfeldt-Jakob disease (CJD) raised concerns that one of the hallmark lesions of Alzheimer disease (AD), amyloid-β (Aβ), may be transmitted from human-to-human. The neuropathology of AD-related lesions is complex. Therefore, many aspects need to be considered in deciding on this issue. Observations of recent studies can be summarized as follows: 1) The frequency of iatrogenic CJD cases with parencyhmal and vascular Aβ deposits is statistically higher than expected; 2) The morphology and distribution of Aβ deposition may show distinct features; 3) The pituitary and the dura mater themselves may serve as potential sources of Aβ seeds; 4) Cadaveric dura mater from 2 examined cases shows Aβ deposition; and 5) There is a lack of evidence that the clinical phenotype of AD appears following the application of cadaveric pituitary hormone or dura mater transplantation. These studies support the notion that neurodegenerative diseases have common features regarding propagation of disease-associated proteins as seeds. However, until further evidence emerges, prions of transmissible spongiform encephalopathies are the only neurodegenerative disease-related proteins proven to propagate clinicopathological phenotypes.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  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. 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

  9. 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 ...

  10. Smoking and Progression of Alzheimers Disease: Connecting Edges

    Directory of Open Access Journals (Sweden)

    Vivek Sharma

    2014-06-01

    Full Text Available Smoking is a practice to burn and inhale the smoke and is primarily a route of administration for recreational drugs. The combustion releases the active substances in drugs such as nicotine and make them available for absorption through the lungs.The most common form of smoking is ciggarate smoking and is associated with life threatening complications like heart diseases, lung cancer, atherosclerosis, rheumatoid arthritis, osteoporosios, immune system dysfunction, hypertension, chronic obstructive pulmonary diseases, miscarriage, premature birth and dysfunctions of reproductive system as well. Smoking affet almost every organ of the body however, compared to the volume of research on the cardiovascular, pulmonary and cancer related health consequences of chronic smoking, lesser attention has been devoted to investigation of its effects on human neurocognition and brain neurobiology. In central nervous system, it leads to deficiencies in auditory verbal learning and/or memory, general intellectual abilities, visual search speeds, processing speed, cognitive flexibility, working memory and executive functions across a wide age range. The present work makes an effort to compile the evidence to challenge the notion/myth that smoking may be neuroprotective in cases of Alzheimers disease. The neuroprotective effects of smoking may be accredited only to nicotinic content of cigarrate smoke that too in part, but smoke is a deadly mixture of thousands of chemicals that must have disastrous effect on central nervous system. The various effets of cigarrate smoke and its ingredients on pathological markers of Alzheimers disease as oxidative stress, senile plaques, tau hyperphosphorylation, neuroinflammation, synapse loss and effects on blood brain barrier are disussed. [Archives Medical Review Journal 2014; 23(3.000: 534-561

  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. CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    J. Thome

    2011-01-01

    Full Text Available Disturbed circadian rhythms with sleep problems and disrupted diurnal activity are often seen in patients suffering from Alzheimer disease (AD. Both endogenous CLOCK genes and external Zeitgeber are responsible for the maintenance of circadian rhythmicity in humans. Therefore, modifications of the internal CLOCK system and its interactions with exogenous factors might constitute the neurobiological basis for clinically observed disruptions in rhythmicity, which often have grave consequences for the quality of life of patients and their caregivers. Presently, more and more data are emerging demonstrating how alterations of the CLOCK gene system might contribute to the pathophysiology of AD and other forms of dementia. At the same time, the impact of neuropsychiatric medication on CLOCK gene expression is under investigation.

  13. Emerging therapeutics for Alzheimer's disease: an avenue of hope.

    Science.gov (United States)

    Samuels, Steven C; Grossman, Hillel

    2003-11-01

    Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavy metal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyperphosphorylation of Tau are other approaches in research and development.

  14. Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease

    International Nuclear Information System (INIS)

    Wolozin, B.; Scicutella, A.; Davies, P.

    1988-01-01

    ALZ-50 is a monoclonal antibody that recognizes a protein of apparent molecular mass 68 kilodaltons (A68). The protein is present in the brains of patients with Alzheimer disease but is not detectable in normal adult brain tissue. The authors report that ALZ-50-reactive neurons are found in normal fetal and neonatal human brain and in brain tissue from neonatal individuals with Down syndrome. Reactive neurons decrease sharply in number after age 2 and reappear in older individuals with Down syndrome and in patients with Alzheimer disease

  15. Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is stimulus-dependent

    DEFF Research Database (Denmark)

    Hartlage-Rübsamen, Maike; Zeitschel, Ulrike; Apelt, Jenny

    2003-01-01

    The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental...... paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients....

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Xiaochuan Wang

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

  6. 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.

  7. 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

  8. Alzheimer's disease markers in the aged sheep (Ovis aries).

    Science.gov (United States)

    Reid, Suzanne J; Mckean, Natasha E; Henty, Kristen; Portelius, Erik; Blennow, Kaj; Rudiger, Skye R; Bawden, C Simon; Handley, Renee R; Verma, Paul J; Faull, Richard L M; Waldvogel, Henry J; Zetterberg, Henrik; Snell, Russell G

    2017-10-01

    This study reports the identification and characterization of markers of Alzheimer's disease (AD) in aged sheep (Ovis aries) as a preliminary step toward making a genetically modified large animal model of AD. Importantly, the sequences of key proteins involved in AD pathogenesis are highly conserved between sheep and human. The processing of the amyloid-β (Aβ) protein is conserved between sheep and human, and sheep Aβ 1-42 /Aβ 1-40 ratios in cerebrospinal fluid (CSF) are also very similar to human. In addition, total tau and neurofilament light levels in CSF are comparable with those found in human. The presence of neurofibrillary tangles in aged sheep brain has previously been established; here, we report for the first time that plaques, the other pathologic hallmark of AD, are also present in the aged sheep brain. In summary, the biological machinery to generate the key neuropathologic features of AD is conserved between the human and sheep, making the sheep a good candidate for future genetic manipulation to accelerate the condition for use in pathophysiological discovery and therapeutic testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Sennvik, Kristina; Nilsberth, Camilla; Stenh, Charlotte

    2002-01-01

    The E693G (Arctic) mutation of the amyloid precursor protein was recently found to lead to early-onset Alzheimer's disease in a Swedish family. In the present study, we report that the Arctic mutation decreases cell viability in human neuroblastoma cells. The cell viability, as measured by the MTT...... their secretion of beta-secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic stress in cells with the Arctic mutation most likely contributes to the pathogenic pathway leading to Alzheimer's disease....

  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. Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease.

    Science.gov (United States)

    Watson, Corey T; Roussos, Panos; Garg, Paras; Ho, Daniel J; Azam, Nidha; Katsel, Pavel L; Haroutunian, Vahram; Sharp, Andrew J

    2016-01-19

    Alzheimer's disease affects ~13% of people in the United States 65 years and older, making it the most common neurodegenerative disorder. Recent work has identified roles for environmental, genetic, and epigenetic factors in Alzheimer's disease risk. We performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 platform on bulk tissue samples from the superior temporal gyrus of patients with Alzheimer's disease and non-demented controls. We paired a sliding window approach with multivariate linear regression to characterize Alzheimer's disease-associated differentially methylated regions (DMRs). We identified 479 DMRs exhibiting a strong bias for hypermethylated changes, a subset of which were independently associated with aging. DMR intervals overlapped 475 RefSeq genes enriched for gene ontology categories with relevant roles in neuron function and development, as well as cellular metabolism, and included genes reported in Alzheimer's disease genome-wide and epigenome-wide association studies. DMRs were enriched for brain-specific histone signatures and for binding motifs of transcription factors with roles in the brain and Alzheimer's disease pathology. Notably, hypermethylated DMRs preferentially overlapped poised promoter regions, marked by H3K27me3 and H3K4me3, previously shown to co-localize with aging-associated hypermethylation. Finally, the integration of DMR-associated single nucleotide polymorphisms with Alzheimer's disease genome-wide association study risk loci and brain expression quantitative trait loci highlights multiple potential DMRs of interest for further functional analysis. We have characterized changes in DNA methylation in the superior temporal gyrus of patients with Alzheimer's disease, highlighting novel loci that facilitate better characterization of pathways and mechanisms underlying Alzheimer's disease pathogenesis, and improve our understanding of epigenetic signatures that may contribute to the

  19. 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

  20. 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.

  1. Different Populations of Human Locus Ceruleus Neurons Contain Heavy Metals or Hyperphosphorylated Tau: Implications for Amyloid-β and Tau Pathology in Alzheimer's Disease.

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2015-01-01

    A marked loss of locus ceruleus (LC) neurons is a striking pathological feature of Alzheimer's disease (AD). LC neurons are particularly prone to taking up circulating toxicants such as heavy metals, and hyperphosphorylated tau (tau(HYP)) appears early in these neurons. In an attempt to find out if both heavy metals and tau(HYP) could be damaging LC neurons, we looked in the LC neurons of 21 sporadic AD patients and 43 non-demented controls for the heavy metals mercury, bismuth, and silver using autometallography, and for tau(HYP) using AT8 immunostaining. Heavy metals or tau(HYP) were usually seen in separate LC neurons, and rarely co-existed within the same neuron. The number of heavy metal-containing LC neurons did not correlate with the number containing tau(HYP). Heavy metals therefore appear to occupy a mostly different population of LC neurons to those containing tau(HYP), indicating that the LC in AD is vulnerable to two different assaults. Reduced brain noradrenaline from LC damage is linked to amyloid-β deposition, and tau(HYP) in the LC may seed neurofibrillary tangles in other neurons. A model is described, incorporating the present findings, that proposes that the LC plays a part in both the amyloid-β and tau pathologies of AD.

  2. 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 ...

  3. Gains and losses on the road to understanding Alzheimer's disease.

    Science.gov (United States)

    Konietzko, Uwe

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause for dementia, which affects approximately 120 thousand people in Switzerland and 35 million worldwide. Aging is a major risk factor for developing AD and thus, as our societies are growing older, we face great challenges to find treatment strategies. The disease is characterised by loss of memory, deposition of extracellular amyloid plaques containing Aβ peptides and intraneuronal tangles of the tau protein. To date, there is no effective treatment and the cause of the disease is still debated. The Schweizerische Alzheimervereinigung states that we need "continuous manifold research" into all possible causes of AD to find a cure for this disease. Fitting this proposition, a recent publication by Xia et al. (2015) described a novel mouse model that for the first time reproduces cortical neuron death as observed in human AD cases. At the same time, this publication questions the major theory of AD pathogenesis and points towards different treatment avenues that should be followed to find a cure for AD.

  4. The Zinc Dyshomeostasis Hypothesis of Alzheimer's Disease

    Science.gov (United States)

    Craddock, Travis J. A.; Tuszynski, Jack A.; Chopra, Deepak; Casey, Noel; Goldstein, Lee E.; Hameroff, Stuart R.; Tanzi, Rudolph E.

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized

  5. The zinc dyshomeostasis hypothesis of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Travis J A Craddock

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ, intracellular neurofibrillary tangles (NFTs composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau, and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1 used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2 performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3 used metallomic imaging mass spectrometry (MIMS to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of

  6. Apathy and Attentional Biases in Alzheimer's Disease.

    Science.gov (United States)

    Chau, Sarah A; Chung, Jonathan; Herrmann, Nathan; Eizenman, Moshe; Lanctôt, Krista L

    2016-01-01

    Apathy, one of the most prevalent neuropsychiatric symptoms in Alzheimer's disease (AD), can be difficult to assess as cognition deteriorates. There is a need for more objective assessments that do not rely on patient insight, communicative capacities, or caregiver observation. We measured visual scanning behavior, using an eye-tracker, to explore attentional bias in the presence of competing stimuli to assess apathy in AD patients. Mild-to-moderate AD patients (Standardized Mini-Mental Status Examination, sMMSE >10) were assessed for apathy (Neuropsychiatric Inventory [NPI] apathy, Apathy Evaluation Scale [AES]). Participants were presented with 16 slides, each containing 4 images of different emotional themes (2 neutral, 1 social, 1 dysphoric). The duration of time spent, and fixation frequency on images were measured. Of the 36 AD patients (14 females, age = 78.2±7.8, sMMSE = 22.4±3.5) included, 17 had significant apathy (based on NPI apathy ≥4) and 19 did not. These groups had comparable age and sMMSE. Repeated-measures analysis of covariance models, controlling for total NPI, showed group (apathetic versus non-apathetic) by image (social versus dysphoric) interactions for duration (F(1,32) = 4.31, p = 0.046) and fixation frequency (F(1,32) = 11.34, p = 0.002). Apathetic patients demonstrated reduced duration and fixation frequency on social images compared with non-apathetic patients. Additionally, linear regression models suggest that more severe apathy predicted decreasing fixation frequency on social images (R2 = 0.26, Adjusted R2 = 0.19, F(3,32) = 3.65, p = 0.023). These results suggest that diminished attentional bias toward social-themed stimuli is a marker of apathy in AD. Measurements of visual scanning behavior may have the potential to predict and monitor treatment response in apathy.

  7. Globalization of Alzheimer's disease clinical trials

    Science.gov (United States)

    2011-01-01

    Alzheimer's disease (AD) therapies are increasingly being tested in global clinical trials. A search of ClincalTrials.gov revealed that of 269 currently active trials, 28% are currently being conducted in the United States; the majority of trials and the majority of trial sites are ex-US. The US has the largest number of trial sites of any single country; cumulatively, nearly half of all sites are outside the US. The US conducts more trials in all phases of drug development but has a greater proportion of phase 3 trials. The increasing importance of global participants in clinical trials emphasizes the importance of considering the ethnic and international factors that may influence trial outcome. The International Conference on Harmonization guidelines divide ethnic factors that may affect drug development into intrinsic and extrinsic influences. These include language, cultural factors, educational levels, the general level of health and standard of care, as well as nutrition and diet. Ethnic influences on pharmacokinetics are known for some metabolic pathways. The biology of AD may also differ among the world's populations. The frequency of the apolipoprotein e4 allele, a major risk factor for AD, differs internationally. Genetic variations might also affect inflammatory, excitotoxic, and oxidative components of AD. Diagnostic standards and experience vary from country to country. Levels of practitioner training and experience, diagnostic approaches to AD, and attitudes regarding aging and AD may differ. Experience and sophistication with regard to clinical trial conduct also vary within and between countries. Experience with conducting the necessary examinations, as well as the linguistic and cultural validity of instrument translations, may affect trial outcomes. Operational and regulatory aspects of clinical trials vary and provide important barriers to seamless conduct of multiregional clinical trials. Collection and testing of biological samples, continuous

  8. Globalization of Alzheimer's disease clinical trials.

    Science.gov (United States)

    Cummings, Jeffrey; Reynders, Robert; Zhong, Kate

    2011-08-17

    Alzheimer's disease (AD) therapies are increasingly being tested in global clinical trials. A search of ClincalTrials.gov revealed that of 269 currently active trials, 28% are currently being conducted in the United States; the majority of trials and the majority of trial sites are ex-US. The US has the largest number of trial sites of any single country; cumulatively, nearly half of all sites are outside the US. The US conducts more trials in all phases of drug development but has a greater proportion of phase 3 trials. The increasing importance of global participants in clinical trials emphasizes the importance of considering the ethnic and international factors that may influence trial outcome. The International Conference on Harmonization guidelines divide ethnic factors that may affect drug development into intrinsic and extrinsic influences. These include language, cultural factors, educational levels, the general level of health and standard of care, as well as nutrition and diet. Ethnic influences on pharmacokinetics are known for some metabolic pathways. The biology of AD may also differ among the world's populations. The frequency of the apolipoprotein e4 allele, a major risk factor for AD, differs internationally. Genetic variations might also affect inflammatory, excitotoxic, and oxidative components of AD. Diagnostic standards and experience vary from country to country. Levels of practitioner training and experience, diagnostic approaches to AD, and attitudes regarding aging and AD may differ. Experience and sophistication with regard to clinical trial conduct also vary within and between countries. Experience with conducting the necessary examinations, as well as the linguistic and cultural validity of instrument translations, may affect trial outcomes. Operational and regulatory aspects of clinical trials vary and provide important barriers to seamless conduct of multiregional clinical trials. Collection and testing of biological samples, continuous

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  10. Ten Challenges of the Amyloid Hypothesis of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...... as a background model of the disease, unify our understanding of the interplay between genetic and non-genetic risk factors, and combine into one framework both the familial and sporadic forms of the disease....

  11. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Gargini, Ricardo; García, Esther; Perry, George

    2017-01-01

    Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

  12. Music therapy and Alzheimer's disease: Cognitive, psychological, and behavioural effects.

    Science.gov (United States)

    Gómez Gallego, M; Gómez García, J

    2017-06-01

    Music therapy is one of the types of active ageing programmes which are offered to elderly people. The usefulness of this programme in the field of dementia is beginning to be recognised by the scientific community, since studies have reported physical, cognitive, and psychological benefits. Further studies detailing the changes resulting from the use of music therapy with Alzheimer patients are needed. Determine the clinical improvement profile of Alzheimer patients who have undergone music therapy. Forty-two patients with mild to moderate Alzheimer disease underwent music therapy for 6 weeks. The changes in results on the Mini-mental State Examination, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale and Barthel Index scores were studied. We also analysed whether or not these changes were influenced by the degree of dementia severity. Significant improvement was observed in memory, orientation, depression and anxiety (HAD scale) in both mild and moderate cases; in anxiety (NPI scale) in mild cases; and in delirium, hallucinations, agitation, irritability, and language disorders in the group with moderate Alzheimer disease. The effect on cognitive measures was appreciable after only 4 music therapy sessions. In the sample studied, music therapy improved some cognitive, psychological, and behavioural alterations in patients with Alzheimer disease. Combining music therapy with dance therapy to improve motor and functional impairment would be an interesting line of research. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. 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...

  14. Rivastigmine in the treatment of hypersexuality in Alzheimer disease.

    Science.gov (United States)

    Canevelli, Marco; Talarico, Giuseppina; Tosto, Giuseppe; Troili, Fernanda; Lenzi, Gian Luigi; Bruno, Giuseppe

    2013-01-01

    Inappropriate sexual behaviors (ISB) represent uncommon and often misdiagnosed clinical disorders among patients with Alzheimer disease. So far, no randomized clinical trials regarding the treatment of ISB in demented people have been conducted, but available data from case series and isolated case reports suggest the efficacy of selective serotonin reuptake inhibitors (SSRIs), antipsychotics, antiandrogens, and H2-receptor antagonists. Controversial data exist on the therapeutic influence of cholinesterase inhibitors on sexual disorders. In the present article, we describe the case of an Alzheimer disease patient presenting hypersexuality, successfully treated with rivastigmine. Thus, we perform a revision of the existing literature regarding the therapeutical effect of cholinesterase inhibitors in the treatment of ISB.

  15. Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer's Disease induced Albino Rats.

    Science.gov (United States)

    Nimgampalle, Mallikarjuna; Kuna, Yellamma

    2017-08-01

    Alzheimer's disease is a type of dementia, and till now there is no suitable drug available for the complete cure of this disease. Now-a-days Probiotics, Lactobacillus strains play a therapeutic role in cognitive disorders through Gut-Brain Axis communication. The present study was aimed to evaluate the anti-Alzheimer properties of Lactobacillus plantarum MTCC1325 against D-Galactose-induced Alzheimer's disease in albino rats. Healthy rats (48) of wistar strain were divided into four groups viz., Group-I: control rats received saline, Group-II: rats received intraperitoneal injection of D-Galactose (120 mg/kg body weight) throughout experiment, Group-III: initially animals were subjected to D-Galactose injection for six weeks, then followed by simultaneously received both D-Galactose and L. plantarum MTCC1325 (12×10 8 CFU/ml; 10 ml/kg body weight) for 60 days and Group-IV: rats which were orally administered only with Lactobacillus plantarum MTCC1325 for 60 days. During the experimentation, both morphometric and behavioural aspects were studied. Later we have examined histopathological changes and estimated cholinergic levels in selected brain regions of all experimental groups of rats including control on selected days. Morphometric, behavioural changes, ACh levels were significantly decreased and pathological hallmarks such as amyloid plaques and tangles were also observed in AD model group. Treatment of AD-group with L. plantarum MTCC1325 for 60 days, not only ameliorated cognition deficits but also restored ACh and the histopathological features to control group. However, no significant effects have been observed in the group treated with L. plantarum alone. The study revealed that, L. plantarum MTCC1325 might have anti-Alzheimer properties against D-Galactose induced Alzheimer's disease.

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

    OpenAIRE

    Tang, Jun

    2012-01-01

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

  17. Reduction of Alzheimer's disease beta-amyloid pathology in the absence of gut microbiota

    OpenAIRE

    Harach, T.; Marungruang, N.; Dutilleul, N.; Cheatham, V.; Coy, K. D. Mc; Neher, J. J.; Jucker, M.; Fåk, F.; T.; Lasser; Bolmont, T.

    2015-01-01

    Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease a...

  18. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    Science.gov (United States)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  19. 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,

  20. Demencia en la enfermedad de Alzheimer: un enfoque integral Dementia in Alzheimer's disease: a comprehensive approach

    Directory of Open Access Journals (Sweden)

    Víctor T. Pérez Martínez

    2005-08-01

    Full Text Available El substrato patológico de la principal de las demencias, lo constituyen las siguientes lesiones: la degeneración neurofibrilar abundante y difusa, las placas neuríticas y el depósito anormal de sustancia amiloide en el cerebro, causante de la toxicidad cerebral. La demencia en la enfermedad de Alzheimer cumple con un patrón clínico-topográfico de tipo cortical característico. Su diagnóstico definitivo es anatomopatológico, pero se puede establecer un diagnóstico probable basado en la clínica y en la evaluación neuropsicológica. No existe tratamiento efectivo concluyente para el deterioro cognitivo de la enfermedad de Alzheimer.The pathological substrate of the main dementia is composed of the following lesions: the diffuse and abundant neurofibrillar degeneration, the neuritic plaques and the abnormal deposit of amyloid substance in the brain, causing cerebral toxicity. Dementia in Alzheimer's disease accomplishes a clinicotopographic pattern of characteristic cortical type. Its definitive diagnosis is anatomopathological, but a probable diagnosis based on the clinic and the neuropsychological evaluation can be established. There is no a concluding effective treatment for the cognitive deterioration of Alzheimer's disease.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  3. 'Too much good news' - are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer's disease?

    Science.gov (United States)

    Zahs, Kathleen R; Ashe, Karen H

    2010-08-01

    Scores of compounds ameliorate cognitive deficits or neuropathology in transgenic mouse models of Alzheimer's disease (AD), yet these triumphs in mice have not translated into successful therapies for people. Why have studies in mice failed to predict results of human trials? We argue that most transgenic mouse 'models of AD' actually simulate the asymptomatic phase of the disease, and the results of interventional studies in these mice should be considered in the context of disease prevention. In addition, recent advances in imaging technology and biomarker discovery should aid in comparisons of mouse and human neurological status and, importantly, might allow us to predict better the response of people to drugs tested in mice. Copyright 2010. Published by Elsevier Ltd.

  4. A state of delirium: Deciphering the effect of inflammation on tau pathology in Alzheimer's disease

    OpenAIRE

    Barron, Matthew; Gartlon, Jane; Dawson, Lee A.; Atkinson, Peter J.; Pardon, Marie-Christine

    2017-01-01

    Alzheimer's disease (AD), the predominant form of dementia, is highly correlated with the abnormal hyperphosphorylation and aggregation of tau. Immune responses are key drivers of AD and how they contribute to tau pathology in human disease remains largely unknown. This review summarises current knowledge on the association between inflammatory processes and tau pathology. While, preclinical evidence suggests that inflammation can indeed induce tau hyperphosphorylation at both pre- and post-t...

  5. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre.

    Science.gov (United States)

    Toledo, Jon B; Arnold, Steven E; Raible, Kevin; Brettschneider, Johannes; Xie, Sharon X; Grossman, Murray; Monsell, Sarah E; Kukull, Walter A; Trojanowski, John Q

    2013-09-01

    Cerebrovascular disease and vascular risk factors are associated with Alzheimer's disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer's Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer's disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 'unremarkable brain' cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer's disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer's disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer

  6. Caffeine and coffee as therapeutics against Alzheimer's disease.

    Science.gov (United States)

    Arendash, Gary W; Cao, Chuanhai

    2010-01-01

    Epidemiologic studies have increasingly suggested that caffeine/coffee could be an effective therapeutic against Alzheimer's disease (AD). We have utilized a transgenic mouse model for AD in well-controlled studies to determine if caffeine and/or coffee have beneficial actions to protect against or reverse AD-like cognitive impairment and AD pathology. AD mice given caffeine in their drinking water from young adulthood into older age showed protection against memory impairment and lower brain levels of the abnormal protein (amyloid-beta; Abeta) thought to be central to AD pathogenesis. Moreover, "aged" cognitively-impaired AD mice exhibited memory restoration and lower brain Abeta levels following only 1-2 months of caffeine treatment. We believe that the cognitive benefits of chronic caffeine administration in AD mice are due to caffeine itself, and not metabolites of caffeine; this, because our long-term administration of theophylline to AD mice provided no cognitive benefits. In acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels - similarly rapid alterations in plasma Abeta levels were seen in humans following acute caffeine administration. "Caffeinated" coffee provided to AD mice also quickly decreased plasma Abeta levels, but not "decaffeinated" coffee, suggesting that caffeine is critical to decreasing blood Abeta levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Abeta production through suppression of both beta- and gamma-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans.

  7. Retinal pathology as biomarker for cognitive impairment and Alzheimer's disease

    NARCIS (Netherlands)

    M.K. Ikram (Kamran); C.Y.-L. Cheung (Carol Yim-Lui); T.Y. Wong (Tien Yin); C. Chen (Christopher)

    2012-01-01

    textabstractAlzheimer's disease (AD) is the most common cause of dementia. Furthermore, over the last few decades, there has been a shift towards identifying earlier stages of AD, which include mild cognitive impairment (MCI). Improved methods of screening and early detection are essential to

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

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Andreasen T., Jesper; Arvaniti, Maria

    2016-01-01

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

  9. Use of unproven therapies by people with Alzheimer's disease.

    Science.gov (United States)

    Coleman, L M; Fowler, L L; Williams, M E

    1995-07-01

    To describe the use of unproven therapies for Alzheimer's disease. Descriptive survey using a written questionnaire. 101 primary caregivers of people with Alzheimer's disease who attended Alzheimer's disease support group meetings. Fifty-five percent of caregivers reported that they had tried at least one alternative therapy to improve the patient's memory. Twenty percent of caregivers tried three or more unproven therapies. Vitamins were used most frequently (84%), and health foods (27%), herbal medicines (11%), "smart pills" (9%), and home remedies (7%) were also tried. Most caregivers reported trying the therapies in the early stage of the illness and did not notice significant improvement in the patient's memory. Twenty-five percent of caregivers had tried unproven therapies for behavior problems. There was no correlation between the use of alternative therapies and the sex of the caregiver, age of the caregiver, level of caregiver frustration, presence of problem behaviors, or perceived level of physician support. The use of unproven therapies by people with early Alzheimer's disease is common and cannot be predicted by characteristics of the primary caregiver. Although this use may be understandable, it exposes vulnerable people to possible side effects, increased costs, and possible exploitation. Health care workers should actively inquire about the use of alternative therapies, and explore the reasons behind their use, so that they can better understand and meet the needs of their patients and their caregivers.

  10. Cardiovascular risk factors and future risk of Alzheimer's disease

    NARCIS (Netherlands)

    R.F.A.G. de Bruijn (Renée); M.A. Ikram (Arfan)

    2014-01-01

    textabstractAlzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize

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

    Science.gov (United States)

    Taler, Vanessa; Chertkow, Howard; Saumier, Daniel

    2005-01-01

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

  12. Investigational medications for treatment of patients with Alzheimer disease.

    Science.gov (United States)

    Potter, Pamela E

    2010-09-01

    Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.

  13. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012

    Science.gov (United States)

    2012-11-06

    ... irreversible, fatal illness that robs men and women of their cherished memories and leads to progressive mental... Disease. The Plan lays out a bold vision for Alzheimer's prevention and treatment, calling for a... continues to take a heartbreaking toll on millions of lives. As we honor the memory of those we have lost...

  14. Financial Conflicts Facing Late-Life Remarried Alzheimer's Disease Caregivers

    Science.gov (United States)

    Sherman, Carey Wexler; Bauer, Jean W.

    2008-01-01

    This qualitative study explores financial conflicts faced by late-life remarried wives providing care for their husbands with Alzheimer's disease. Interviews with 9 women identified intergenerational secrets and tensions regarding financial and inheritance decisions. Participants' remarried spouse status, underlying family boundary ambiguities,…

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

    Science.gov (United States)

    Williamson, Gail M.; Schulz, Richard

    1993-01-01

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

  16. A Psychoeducational Model for Hispanic Alzheimer's Disease Caregivers

    Science.gov (United States)

    Morano, Carmen L.; Bravo, Marina

    2002-01-01

    Purpose: More than 14 million persons are projected to be diagnosed with Alzheimer's disease (AD) by the year 2020; therefore, it is not surprising that the literature contains numerous caregiver intervention studies. What is surprising is that although minority elders represent one of the fastest growing segments of the older population, they are…

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

    Science.gov (United States)

    Talkington-Boyer, Shannon; Snyder, Douglas K.

    1994-01-01

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

  18. Diagnostic dilemmas in Alzheimer's disease: Room for shared decision making

    NARCIS (Netherlands)

    van der Flier, Wiesje M.; Kunneman, Marleen; Bouwman, Femke H.; Petersen, Ronald C.; Smets, Ellen M. A.

    2017-01-01

    The launch of the NIA-AA research criteria for Alzheimer's disease (AD) diagnosis illustrates the large advances that have been made in the field of AD diagnosis. These new possibilities however also introduce new dilemmas into the consulting room, and this provides room for shared decision making

  19. Support Groups for Family Caregivers of Patients with Alzheimer's Disease.

    Science.gov (United States)

    Wasow, Mona

    1986-01-01

    Discusses some assumptions, dilemmas, and questions in (1) facilitating support groups for caregivers whose relatives have Alzheimer's disease, (2) talking with other such facilitators around the country, (3) reviewing the literature, and (4) talking with group members themselves. Suggestions are made for a wider variety of support-group models.…

  20. Differential Effects of Family-Based Strategies on Alzheimer's Disease.

    Science.gov (United States)

    Quayhagen, Mary P.; Quayhagen, Margaret

    1989-01-01

    Assessed efficacy of home-based program of cognitive stimulation for functional status of patients with Alzheimer's disease and their caregivers. Compared treated caregiver/patient dyads with nontreated dyads. Results suggest that treated patients exhibited maintenance levels of cognitive and behavioral functioning and improved emotionally while…