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Sample records for alzheimer disease-like clinical

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and...... hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited...

  2. 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.

  3. Stress acts cumulatively to precipitate Alzheimer's disease-like tau pathology and cognitive deficits.

    Science.gov (United States)

    Sotiropoulos, Ioannis; Catania, Caterina; Pinto, Lucilia G; Silva, Rui; Pollerberg, G Elizabeth; Takashima, Akihiko; Sousa, Nuno; Almeida, Osborne F X

    2011-05-25

    Stressful life experiences are likely etiological factors in sporadic forms of Alzheimer's disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid β (Aβ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused Aβ to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in Aβ-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition. PMID:21613497

  4. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's Disease-Like Murine Model.

    Science.gov (United States)

    Ehrhart, Jared; Darlington, Donna; Kuzmin-Nichols, Nicole; Sanberg, Cyndy D; Sawmiller, Darrell R; Sanberg, Paul R; Tan, Jun

    2016-01-01

    Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or adult stem cells, have emerged as effective and relatively safe immunomodulators and neuroprotectors, reducing behavioral impairment in animal models of Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and stroke. In this report, we followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice or rats at a single dose of 1 × 10(6) or 2.2 × 10(6) cells, respectively, prior to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For determination of HUCBC distribution, tissues from both species were subjected to total DNA isolation and polymerase chain reaction (PCR) amplification of the gene for human glycerol-3-phosphate dehydrogenase. Our results show a relatively similar biodistribution and retention of HUCBCs in both mouse and rat organs. HUCBCs were broadly detected both in the brain and several peripheral organs, including the liver, kidney, and bone marrow, of both species, starting within 7 days and continuing up to 30 days posttransplantation. No HUCBCs were recovered in the peripheral circulation, even at 24 h posttransplantation. Therefore, HUCBCs reach several tissues including the brain following a single intravenous treatment, suggesting that this route can be a viable method of administration of these cells for the treatment of neurodegenerative diseases. PMID:26414627

  5. Treadmill exercise prevents learning and memory impairment in Alzheimer's disease-like pathology.

    Science.gov (United States)

    Dao, An T; Zagaar, Munder A; Levine, Amber T; Salim, Samina; Eriksen, Jason L; Alkadhi, Karim A

    2013-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive memory loss. In contrast, accumulating evidence suggests a neuroprotective role of regular exercise in aging associated memory impairment. In this study, we investigated the ability of regular exercise to prevent impairments of short-term memory (STM) and early long-term potentiation (E-LTP) in area CA1 of the hippocampus in a rat model of AD (i.c.v. infusion of 250 pmol/day Aβ1-42 peptides). We utilized behavioral assessment, in vivo electrophysiological recording, and immunoblotting in 4 groups of adult Wistar rats: control, treadmill exercise (Ex), β-amyloid-infused (Aβ), and amyloid-infused/treadmill exercised (Ex/Aβ). Our findings indicated that Aβ rats made significantly more errors in the radial arm water maze (RAWM) compared to all other groups and exhibited suppressed E-LTP in area CA1, which correlated with deleterious alterations in the levels of memory and E-LTP-related signaling molecules including calcineurin (PP2B), brain derivedneurotrophic factor (BDNF) and phosphorylated CaMKII (p-CaMKII). Compared to controls, Ex and Ex/Aβ rats showed a similar behavioral performance and a normal E-LTP with no detrimental changes in the levels of PP2B, BDNF, and p- CaMKII. We conclude that treadmill exercise maybe able to prevent cognitive impairment associated with AD pathology. PMID:23627709

  6. Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dani M Long

    Full Text Available Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD, are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01. No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism.

  7. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    Science.gov (United States)

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  8. Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

    OpenAIRE

    Guilherme Riccioppo Rodrigues; Walker, Ruth H.; Benedikt Bader; Adrian Danek; Alexis Brice; Cécile Cazeneuve; Odile Russaouen; Iscia Lopes-Cendes; Wilson Marques Jr; Vitor Tumas

    2011-01-01

    Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidol...

  9. Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?

    Directory of Open Access Journals (Sweden)

    Gabrielle M. de Courten-Myers

    2010-01-01

    Full Text Available Down's syndrome (DS, trisomy 21 represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD. We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42 burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of Aβ42 could relate to the cases' similar life-time accumulation of Aβ due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP. The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of Aβ42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary. Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis.

  10. Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype

    Directory of Open Access Journals (Sweden)

    Guilherme Riccioppo Rodrigues

    2011-06-01

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington's disease-like 2 (HDL2, spinocerebellar ataxia (SCA 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA and chorea-acanthocytosis (ChAc among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype.

  11. Time trend in Alzheimer diagnoses and the association between distance to an Alzheimer clinic and Alzheimer diagnosis

    DEFF Research Database (Denmark)

    Jørgensen, Terese Sara Høj; Torp-Pedersen, Christian; Gislason, Gunnar H.;

    2015-01-01

    BACKGROUND: Centralization of specialized health care in Denmark has caused increased geographical distance to health-care providers, which may be a barrier for Alzheimer patients to seek health care. We examined the incidence of Alzheimer diagnosis in Denmark between 2000 and 2009 and investigated...... the association between patients' distance to Alzheimer clinics and Alzheimer diagnoses. METHODS: Data of all individuals aged 65+ years were collected from Danish national registers. Incidences of Alzheimer diagnoses were analysed with joinpoint regression and hazard ratios (HRs) for Alzheimer...... diagnoses were analysed with Cox regressions. RESULTS: The annual incidence of Alzheimer diagnoses increased with 32.5% [95% confidence interval (CI): 7.1-63.8] among individuals aged 65-74 years from 2000 to 2002 and with 29.1% (95% CI: 11.0-50.2) among individuals aged 75+ years from 2000 to 2003. For...

  12. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology

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    Ferretti Maria

    2012-04-01

    Full Text Available Abstract Background A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. Methods and results To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. Conclusions Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology.

  13. Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice

    OpenAIRE

    Rat, Dorothea; Schmitt, Ulrich; Tippmann, Frank; Dewachter, Ilse; Theunis, Clara; Wieczerzak, Ewa; Postina, Rolf; Van Leuven, Fred Van; Fahrenholz, Falk; Kojro, Elzbieta

    2011-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective and neurotrophic properties and is a potent alpha-secretase activator. As PACAP peptides and their specific receptor PAC1 are localized in central nervous system areas affected by Alzheimer's disease (AD), this study aims to examine the role of the natural peptide PACAP as a valuable approach in AD therapy. We investigated the effect of PACAP in the brain of an AD transgenic mouse model. The long-term intranasal da...

  14. Neurogenic Responses to Amyloid-Beta Plaques in the Brain of Alzheimer's Disease-Like Transgenic (pPDGF-APPSw,Ind) Mice

    OpenAIRE

    Gan, Li; Qiao, Shuhong; Lan, Xun; Chi, Liying; Luo, Chun; Lien, Lindsey; Liu, Qing Yan; Liu, Rugao

    2007-01-01

    Formation and accumulation of amyloid-beta (Aβ) plaques are associated with declined memory and other neurocognitive function in Alzheimer's Disease (AD) patients. However, the effects of Aβ plaques on neural progenitor cells (NPCs) and neurogenesis from NPCs remain largely unknown. The existing data on neurogenesis in AD patients and AD-like animal models remain controversial. For this reason, we utilized the nestin second-intron enhancer controlled LacZ (pNes-LacZ) reporter transgenic mice ...

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

    International Nuclear Information System (INIS)

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

  16. The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit.

    Science.gov (United States)

    Gruden, Marina A; Davydova, Tatiana V; Wang, Chao; Narkevich, Victor B; Fomina, Valentina G; Kudrin, Vladimir S; Morozova-Roche, Ludmilla A; Sewell, Robert D E

    2016-06-01

    Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and A11 antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy. PMID:26965570

  17. Corticotropin-releasing factor receptor 1 activation during exposure to novelty stress protects against Alzheimer's disease-like cognitive decline in AβPP/PS1 mice.

    Science.gov (United States)

    Scullion, Gillian A; Hewitt, Katherine N; Pardon, Marie-Christine

    2013-01-01

    A lifestyle rich in physical and mental activities protects against Alzheimer's disease (AD) but the underlying mechanisms are unclear. We have proposed that this is mediated by a stress response and have shown that repeated exposure to novelty stress, which induces physical and exploratory activities, delays the progression of AD-like pathology in the TASTPM mouse model. Here, we aimed to establish the role played by corticotrophin-releasing factor receptor 1 (CRFR1), a major component of the stress axis, in TASTPM's behavioral and neuroendocrine responses to novelty and related protective effects. We show that the stress response of TASTPM mice is altered with reduced CRFR1-mediated neuroendocrine and behavioral responses to novelty and a distinct profile of behavioral responses. Repeated novelty-induced CRFR1 activation, however, mediated the improved contextual fear memory and extinction performance of TASTPM mice and increased hippocampal and fronto-cortical levels of synaptophysin, a marker of synaptic density, and fronto-cortical levels of the post-synaptic marker PSD95. The N-methyl-D-aspartate receptor (NMDAR) is the major receptor for synaptic plasticity underlying learning and memory. Although novelty-induced NMDAR activation contributed to enhancement of fear memory and synaptophysin levels, antagonism of CRFR1 and NMDAR prevented the novelty-induced increase in hippocampal synaptophysin levels but reversed the other effects of CRFR1 inactivation, i.e., the enhancement of contextual fear extinction and fronto-cortical synaptophysin and PSD95 levels. These findings suggest a novel mechanism whereby a stimulating environment can delay AD symptoms through CRFR1 activation, facilitating NMDAR-mediated synaptic plasticity and synaptogenesis in a region-dependent manner, either directly, or indirectly, by modulating PSD95. PMID:23302658

  18. T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

    Science.gov (United States)

    Ferretti, M T; Merlini, M; Späni, C; Gericke, C; Schweizer, N; Enzmann, G; Engelhardt, B; Kulic, L; Suter, T; Nitsch, R M

    2016-05-01

    Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. PMID:26872418

  19. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

    International Nuclear Information System (INIS)

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. (author)

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

    Directory of Open Access Journals (Sweden)

    Meng-qiu LI

    2014-03-01

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

  1. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    Energy Technology Data Exchange (ETDEWEB)

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F. [Univ. of South Florida, Tampa, FL (United States)] [and others

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  2. About Alzheimer's Disease: Treatment

    Science.gov (United States)

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

  3. The usefulness of CT scanning in clinical observation on the patients with Alzheimer`s disease; Znaczenie tomografii komputerowej w obserwacji klinicznej pacjentow z choroba Alzheimera

    Energy Technology Data Exchange (ETDEWEB)

    Golebiowski, M.; Barcikowska, M.; Pfeffer-Baczuk, A.; Luczywek, E. [Akademia Medyczna, Warsaw (Poland)

    1994-12-31

    On the basis of brain CT studies of 150 patients of the clinic for persons with Alzheimer`s disease the diagnostic utility of measurement of hippocampal fissure and craniocerebral ratios was assessed. In analyzed group hippocampal fissure measurements greater than 4 mm occurred only in patients with symptoms of Alzheimer`s type dementia. The measurement showed 90% sensitivity and 70% specificity as the prognostic factor of clinical course, especially at the first part of the disease. The evaluation of the hippocampal fissure in conjunction with detailed analysis of CT picture of the atrophic brain allowed for precise final diagnosis. (author). 14 refs, 4 refs.

  4. The genetic landscape of Alzheimer disease: clinical implications and perspectives

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Van Broeckhoven, Christine; Sleegers, Kristel

    2016-01-01

    The search for the genetic factors contributing to Alzheimer disease (AD) has evolved tremendously throughout the years. It started from the discovery of fully penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2 as a cause of autosomal dominant AD, the identification of the ɛ4 allele of Apolipoprotein E as a strong genetic risk factor for both early-onset and late-onset AD, and evolved to the more recent detection of at least 21 additional genetic risk loci for the genetically complex form of AD emerging from genome-wide association studies and massive parallel resequencing efforts. These advances in AD genetics are positioned in light of the current endeavor directing toward translational research and personalized treatment of AD. We discuss the current state of the art of AD genetics and address the implications and relevance of AD genetics in clinical diagnosis and risk prediction, distinguishing between monogenic and multifactorial AD. Furthermore, the potential and current limitations of molecular reclassification of AD to streamline clinical trials in drug development and biomarker studies are addressed. Genet Med 18 5, 421–430. PMID:26312828

  5. Rationale and clinical data supporting nutritional intervention in Alzheimer's disease.

    Science.gov (United States)

    Engelborghs, S; Gilles, C; Ivanoiu, A; Vandewoude, M

    2014-01-01

    Adequate nutrition plays an important role in the maintenance of cognitive function, particularly during aging. Malnutrition is amongst the risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Epidemiological studies have associated deficiencies in some nutrients with a higher risk of cognitive dysfunction and/or AD. Cognitive decline in AD is correlated with synaptic loss and many of the components required to maintain optimal synaptic function are derived from dietary sources. As synapses are part of the neuronal membrane and are continuously being remodelled, the availability of sufficient levels of nutritional precursors (mainly uridine monophosphate, choline and omega-3 fatty acids) to make the phospholipids required to build neuronal membranes may have beneficial effects on synaptic degeneration in AD. In addition, B-vitamins, phospholipids and other micronutrients act as cofactors to enhance the supply of precursors required to make neuronal membranes and synapses. Despite this, no randomized controlled trial has hitherto provided evidence that any single nutrient has a beneficial effect on cognition or lowers the risk for AD. However, a multi-target approach using combinations of (micro)nutrients might have beneficial effects on cognitive function in neurodegenerative brain disorders like AD leading to synaptic degeneration. Here we review the clinical evidence for supplementation, based on a multi-target approach with a focus on key nutrients with a proposed role in synaptic dysfunction. Based on preclinical evidence, a nutrient mixture, Souvenaid(®) (Nutricia N.V., Zoetermeer, The Netherlands) was developed. Clinical trials with Souvenaid(®) have shown improved memory performance in patients with mild AD. Further clinical trials to evaluate the effects of nutritional intervention in MCI and early dementia due to AD are on-going. PMID:24635394

  6. Therapeutic strategies for Alzheimer's disease in clinical trials.

    Science.gov (United States)

    Godyń, Justyna; Jończyk, Jakub; Panek, Dawid; Malawska, Barbara

    2016-02-01

    Alzheimer's disease (AD) is considered to be the most common cause of dementia and is an incurable, progressive neurodegenerative disorder. Current treatment of the disease, essentially symptomatic, is based on three cholinesterase inhibitors and memantine, affecting the glutamatergic system. Since 2003, no new drugs have been approved for treatment of AD. This article presents current directions in the search for novel, potentially effective agents for the treatment of AD, as well as selected promising treatment strategies. These include agents acting upon the beta-amyloid, such as vaccines, antibodies and inhibitors or modulators of γ- and β-secretase; agents directed against the tau protein as well as compounds acting as antagonists of neurotransmitter systems (serotoninergic 5-HT6 and histaminergic H3). Ongoing clinical trials with Aβ antibodies (solanezumab, gantenerumab, crenezumab) seem to be promising, while vaccines against the tau protein (AADvac1 and ACI-35) are now in early-stage trials. Interesting results have also been achieved in trials involving small molecules such as inhibitors of β-secretase (MK-8931, E2609), a combination of 5-HT6 antagonist (idalopirdine) with donepezil, inhibition of advanced glycation end product receptors by azeliragon or modulation of the acetylcholine response of α-7 nicotinic acetylcholine receptors by encenicline. Development of new effective drugs acting upon the central nervous system is usually a difficult and time-consuming process, and in the case of AD to-date clinical trials have had a very high failure rate. Most phase II clinical trials ending with a positive outcome do not succeed in phase III, often due to serious adverse effects or lack of therapeutic efficacy. PMID:26721364

  7. Clinical diagnosis by computed tomography on Alzheimer type dementia

    International Nuclear Information System (INIS)

    The relationships of CT findings, intellectual impairment by psychological assessment and severity of dementia by clinical evaluation were studied on 109 patients with clinical diagnosis of Alzheimer type dementia (AD) and 43 controls. CT examinations were carried out on three tomographic sections, that is, a section through anterior and posterior horns of lateral ventricles, a section through cellae mediae of lateral ventricles and a section through cortex with intracranial space of 60-80 cm2. In the three tomographic sections, CSF space percent and half width full max (HWFM) in the histogram corresponding to brain tissue were employed as indexes of brain atrophy by CT. Psychological evaluation of dementia was made by using Hasegawa's dementia scale (HDS). The present study revealed the following findings. though CSF% in the sections through lateral ventricles significantly correlated with age, it was more significantly correlated with HDS and CDR(clinical dementia rating) scores, respectively. This finding seems to mean that the effect of dementia is so great as to override the effect of dementia. In the cortex slice, the correlations between CSF% and HDS and CDR scores were very low, though they were significant. HWFM in the same slice, showed the moderate and significant correlations with HDS and CDR scores, respectively, comparing with no relationship between HWFM and age. Concerning mean CSF% and HWFM of each group according to CDR staging, they increased with advancement of dementia. The significant differences between the groups by CDR, however, were not always obtained. According to CT indexes as independent variable, the normal subject were discriminated from the demented subjects in 82.6% of the total by discriminat analysis. (J.P.N.)

  8. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  9. Development of screening guidelines and clinical criteria for predementia Alzheimer's disease

    OpenAIRE

    de Visser, P. J.; Verhey, F. R. J.; Boada, M.; Bullock, R; De Deyn, P.P.; Frisoni, G. B.; Frölich, Lutz; Hampel, H.; Jolles, J; Jones, R; Minthon, L.; Nobili, F.; Rikkert, M. Olde; Ousset, P.-J.; Rigaud, A.-S.

    2008-01-01

    Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer...

  10. Clinical Application of 18F-FDG PET in Alzheimer's Disease

    International Nuclear Information System (INIS)

    PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. 18F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, 18F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers 18F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of 18F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases

  11. Clinical Application of {sup 18}F-FDG PET in Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Young Hoon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2008-12-15

    PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. {sup 18}F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, {sup 18}F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers {sup 18}F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of {sup 18}F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases.

  12. A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.

    Science.gov (United States)

    Yu, Yun-Zhou; Liu, Si; Wang, Hai-Chao; Shi, Dan-Yang; Xu, Qing; Zhou, Xiao-Wei; Sun, Zhi-Wei; Huang, Pei-Tang

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine. PMID:27255752

  13. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

    Science.gov (United States)

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. PMID:26528887

  14. The usefulness of CT scanning in clinical observation on the patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    On the basis of brain CT studies of 150 patients of the clinic for persons with Alzheimer's disease the diagnostic utility of measurement of hippocampal fissure and craniocerebral ratios was assessed. In analyzed group hippocampal fissure measurements greater than 4 mm occurred only in patients with symptoms of Alzheimer's type dementia. The measurement showed 90% sensitivity and 70% specificity as the prognostic factor of clinical course, especially at the first part of the disease. The evaluation of the hippocampal fissure in conjunction with detailed analysis of CT picture of the atrophic brain allowed for precise final diagnosis. (author)

  15. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.

    Science.gov (United States)

    Ossenkoppele, Rik; Schonhaut, Daniel R; Schöll, Michael; Lockhart, Samuel N; Ayakta, Nagehan; Baker, Suzanne L; O'Neil, James P; Janabi, Mustafa; Lazaris, Andreas; Cantwell, Averill; Vogel, Jacob; Santos, Miguel; Miller, Zachary A; Bettcher, Brianne M; Vossel, Keith A; Kramer, Joel H; Gorno-Tempini, Maria L; Miller, Bruce L; Jagust, William J; Rabinovici, Gil D

    2016-05-01

    SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent (18)F-AV1451 (tau), (11)C-PiB (amyloid-β) and (18)F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging-contrary to amyloid-β imaging-shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer's disease. Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease. PMID:26962052

  16. Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials.

    Directory of Open Access Journals (Sweden)

    Guoyan Yang

    Full Text Available BACKGROUND: Huperzine A is a Chinese herb extract used for Alzheimer's disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer's disease. METHODS: We searched for randomized clinical trials (RCTs of Huperzine A for Alzheimer's disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249. RESULTS: 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS and Wechsler Memory Scale (WMS at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR. One trial demonstrated no significant change in cognitive function as measured by Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog and activity of daily living as measured by Alzheimer's disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. CONCLUSIONS: Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer's disease. However, the findings should be interpreted with caution due to the poor methodological quality of the

  17. [Dissociation of structural and functional parameters of the retina and optic nerve in a patient with Alzheimer's disease (clinical case)].

    Science.gov (United States)

    Erichev, V P; Panyushkina, L A; Ronzina, I A

    2015-01-01

    Visual impairment is often one of the earliest sings of Alzheimer's disease. This article reports a clinical case of a female patient diagnosed with mild dementia due to Alzheimer's disease. As revealed by a comprehensive examination, her visual fields and visual evoked potentials were markedly changed, while morphometric parameters of the retina and optic nerve appeared normal. Such a significant dissociation of structural and functional parameters may indicate a more proximal involvement of visual pathways in Alzheimer's disease. PMID:26080589

  18. Retrogenesis theory in Alzheimers disease : evidence and clinical implications

    OpenAIRE

    Rogers, Heather; Arango Lasprilla, Juan Carlos

    2006-01-01

    La enfermedad de Alzheimer (EA) es una de las principales causas de muerte en el mundo. El bajo índice de natalidad, la mejora en las condiciones sanitarias y sociales y, como consecuencia, el aumento en la esperanza de vida, han hecho que el número de personas mayores de 65 anos aumente cada vez más. Este aumento en la expectativa de vida ha llevado a que el número de casos nuevos de personas que presentan EA se haya incrementando de manera dramática en los últimos años. Diferentes estudios ...

  19. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    Science.gov (United States)

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  20. A quantitative histological study of early clinical and preclinical Alzheimer's disease.

    Science.gov (United States)

    Hubbard, B M; Fenton, G W; Anderson, J M

    1990-04-01

    Brains from 70 unselected general hospital necropsy cases aged 60-95 years were surveyed histologically for changes of Alzheimer's disease using Congo Red-Gallocyanin preparations. Counts were made of neurofibrillary tangles in two areas of the neocortex, the hippocampal formation and the substantia innominata. Neurons were counted in the subiculum of the hippocampus, the substantia innominata and the locus coeruleus. In addition, a retrospective enquiry was made concerning the mental health of the patients in the study; cognitive performance was graded on the Global Deterioration Scale (GDS 1-7). Four cases (5.7%) had clinical and pathological changes amounting to early Alzheimer's disease. Tangles were very numerous in all areas and there was a 30% deficit or more of neurons in at least two of the structures counted. Although the diagnosis of Alzheimer's disease was not recorded during life, all had shown signs of early cognitive decline (GDS grades 3-6). A further six cases (8.6%) showed excessive tangle accumulation which may represent preclinical Alzheimer's disease. Tangles were present in the temporal neocortex (Brodmann area 22), whereas they were absent in the remainder of the survey. Tangle density in the hippocampal formation (greater than 50 tangles in a 10 microns section) was also above the baseline level of the majority of cases. However, neuron loss was not widespread in these cases and none had shown evidence of cognitive impairment. The findings confirm that the early stages of Alzheimer's disease commonly occur amongst general hospital necropsies. The emergence of clinical signs of dementia appears to be related to the loss of a critical volume of neurons and not to tangle accumulation alone. PMID:2345598

  1. Prospective memory impairments in Alzheimer's Disease and behavioral variant frontotemporal dementia: Clinical and neural correlates

    OpenAIRE

    Dermody, N.; Hornberger, M.; Piguet, O; Hodges, J R; M. Irish

    2015-01-01

    BACKGROUND: Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event-based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. OBJECTIVE: To investigate the clinical ...

  2. Clinical significance of determination of plasma ET and serum NSE, NPY levels in patients with Alzheimer diseases (AD)

    International Nuclear Information System (INIS)

    Objective: To explore the clinical significance of changes of plasma ET and serum NSE, NPY levels in patients with Alzheimer diseases. Methods: Plasma ET and serum NSE, NPY levels were determined with RIA in 31 patients with Alzheimer diseases and 30 controls. Results: The plasma ET and serum NSE, NPY levels in the patients were significantly higher than those in controls (P<0.01). Plasma ET and serum NSE, NPY levels were mutually positively correlated (r=0.4895, 0.6014, P<0.01). Conclusion: Detection of plasma ET and serum NSE, NPY levels was helpful for the prediction of treatment effieacy in patients with Alzheimer diseases. (authors)

  3. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014.

    Science.gov (United States)

    Schneider, L S; Mangialasche, F; Andreasen, N; Feldman, H; Giacobini, E; Jones, R; Mantua, V; Mecocci, P; Pani, L; Winblad, B; Kivipelto, M

    2014-03-01

    The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or 'mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living

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

    Science.gov (United States)

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

    2016-08-01

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

  5. Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting

    Directory of Open Access Journals (Sweden)

    Wallin ÅK

    2011-09-01

    Full Text Available Åsa K Wallin, Carina Wattmo, Lennart MinthonClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenBackground: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD, analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.Methods: Two hundred and eighty patients with a clinical diagnosis of AD were included in the prospective, open-label, multicenter Swedish Alzheimer Treatment Study, and received galantamine treatment. Efficacy measures included cognitive tests, ie, the Mini-Mental State Examination (MMSE and Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog, functional rating (Instrumental Activities of Daily Living Scale [IADL], and global rating. Assessments were carried out before treatment and every six months for a period of three years. K-means cluster analysis was used to identify response subgroups.Results: After three years of treatment, the mean change from baseline was 2.6 points in MMSE and 5.6 points in ADAS-cog scores. Globally, half of the patients improved or remained unchanged for two years. Cluster analysis identified two response clusters. Cluster 1 included patients with low ability in ADAS-cog and IADL scores at baseline. Even though the patients in cluster 1 were older and less educated, they responded better at six months compared with patients in cluster 2. Cluster 2 included patients with better ADAS-cog and IADL scores at baseline. Patients in cluster 2 had a higher frequency of the APOE ε4 allele, a slower pretreatment progression rate, and remained in the study longer than those in cluster 1. Three-year completers (n = 129, 46% received higher doses of galantamine compared with dropouts.Conclusion: AD patients who received long-term galantamine treatment were

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

    Science.gov (United States)

    Jones-Davis, Dorothy M; Buckholtz, Neil

    2015-07-01

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

  7. Clinical significance of white matter hyperintensities in MRI in senile dementia of the Alzheimer type

    International Nuclear Information System (INIS)

    To elucidate clinical significance of white matter hyperintensities (WMH) in MRI, fifty patients with senile dementia of the Alzheimer type (SDAT) and twenty normal controls were studied. Twenty nine patients with SDAT (58.0%) had periventricular hyperintensities (PVH) and twenty three patients with SDAT (46.0%) had deep white matter hyperintensities (DWMH). Eight controls (40.0%) had PVH and ten controls (50.0%) had DWMH. There were no significant differences in frequency of WMH between patients with SDAT and normal controls. Past history of hypertension was more frequent in patients with PVH or DWMH than in patients without them. Serum cholesterol level was higher in patients with DWMH than in patients without them. However there were no significant differences in the other clinical features between patients with WMH and patients without them. The results of present study suggest that DWMH in patients with SDAT is associated with cerebrovascular risk factors such as hypertension and hyperlipidemia. (author)

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

    Science.gov (United States)

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

  9. Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer's disease.

    Science.gov (United States)

    Roeber, Sigrun; Müller-Sarnowski, Felix; Kress, Julia; Edbauer, Dieter; Kuhlmann, Tanja; Tüttelmann, Frank; Schindler, Christoph; Winter, Pia; Arzberger, Thomas; Müller, Ulrich; Danek, Adrian; Kretzschmar, Hans A

    2015-12-01

    Presenilin 1 (PSEN1) mutations are the major cause of autosomal dominant Alzheimer's disease (ADAD). Here we report three novel PSEN1 mutations: Ile238_Lys239insIle, Ala246Pro and Ala164Val from patients who manifested in their twenties, forties and seventies, respectively, with variant clinical presentations of dementia. These cases exemplify the tremendous heterogeneity of clinical phenotypes and age of onset associated with PSEN1 mutations. The possibility of ADAD--not previously suspected in two of our patients--should always be considered in neurodegenerative conditions albeit they might neither exhibit the typical clinical picture of Alzheimer's disease nor early onset dementia, which is regarded the primary clinical sign of hereditary neurodegeneration. PMID:26350633

  10. Correlative study of the brain CT and clinical features of patients with Down's syndrome in three clinical stages of Alzheimer type dementia

    International Nuclear Information System (INIS)

    Patients with Down's syndrome often develop Alzheimer type neuropathological changes as well as dementia of the Alzheimer type after the age of 40. We studied brain CT findings in relation to three clinical stages of Alzheimer type dementia in 11 patients with Down's syndrome aged from 17 to 55 years. In addition, 123I-IMP-SPECT was studied in 4 of these patients. Dementia of the Alzheimer type was present in 9 patients; 5 patients were in the early stage, 2 were in the progressive stage, and the other 2 were in the end stage. The earliest CT finding was enlargement of the suprasellar cistern, which indicated atrophy of the medial temporal lobe including the hippocampus and amygdala. This finding was not present in non-demented individuals with Down's syndrome. Moreover, CT scans showed that brain atrophy progressed to the temporal, frontal lobe, and then generalized cerebral cortices, which correlated clinically with the severity of dementia. Studies of 123I-IMP-SPECT in two patients with mild dementia revealed abnormally decreased isotope uptake in the temporal and posterior parietal regions. We suggest to measure the size of the suprasellar cistern in CT and SPECT scans for early detection and diagnosis of mild dementia of the Alzheimer type in patients with Down's syndrome. (author)

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

    OpenAIRE

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

    2011-01-01

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

  12. Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting

    OpenAIRE

    Wallin, Åsa

    2011-01-01

    Åsa K Wallin, Carina Wattmo, Lennart MinthonClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, SwedenBackground: In the absence of long-term, placebo-controlled studies of cholinesterase inhibitors in Alzheimer's disease (AD), analysis of the results of open-label trials becomes crucial. This study aimed to explore the three-year effects of galantamine treatment, as well as subgroups of response and adherence to treatment.Methods...

  13. Alzheimer's Project

    Medline Plus

    Full Text Available ... dementia What is Alzheimer's Stages of Alzheimer's Treatments Virtual Library Interactive Brain Tour Learn how Alzheimer's affects ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  14. Clinical Benefits of Memantine Treatment for Alzheimer's Disease in the Okayama Memantine Study II (OMS II).

    Science.gov (United States)

    Matsuzono, Kosuke; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Koike, Makoto; Sato, Kota; Kono, Syoichiro; Deguchi, Kentaro; Nakano, Yumiko; Abe, Koji

    2015-01-01

    The clinical benefits of memantine, depending on the baseline cognitive and affective conditions in real world dementia clinics, have not been completely examined. We performed the "Okayama Memantine Study II (OMS II)" to retrospectively evaluate the clinical effects of memantine monotherapy (n = 38) in Alzheimer's disease (AD) patients using seven batteries to assess dementia at the baseline, at 3, 6, and 12 months. Additionally, we divided 163 AD patients treated with memantine into two subgroups depending on the baseline cognitive score of the Mini-Mental State Examination (MMSE): the MMSE BPSD) severity using Abe's BPSD score (ABS). Memantine monotherapy maintained cognitive functions until 6 months of treatment, but showed a decrease at 12 months ( *p BPSD symptoms until 12 months ( *p BPSD severity. Our present OMS II showed that memantine monotherapy improved BPSD until 12 months. The higher baseline cognitive subgroup (MMSE ≥15) and the worse baseline BPSD subgroup were expected to show better effects with memantine. PMID:26401570

  15. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia

    International Nuclear Information System (INIS)

    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer [123I]-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life

  16. Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?

    Science.gov (United States)

    Dekker, Alain D; Strydom, André; Coppus, Antonia M W; Nizetic, Dean; Vermeiren, Yannick; Naudé, Petrus J W; Van Dam, Debby; Potier, Marie-Claude; Fortea, Juan; De Deyn, Peter P

    2015-12-01

    Behavioural and Psychological Symptoms of Dementia (BPSD) are a core symptom of dementia and are associated with suffering, earlier institutionalization and accelerated cognitive decline for patients and increased caregiver burden. Despite the extremely high risk for Down syndrome (DS) individuals to develop dementia due to Alzheimer's disease (AD), BPSD have not been comprehensively assessed in the DS population. Due to the great variety of DS cohorts, diagnostic methodologies, sub-optimal scales, covariates and outcome measures, it is questionable whether BPSD have always been accurately assessed. However, accurate recognition of BPSD may increase awareness and understanding of these behavioural aberrations, thus enabling adaptive caregiving and, importantly, allowing for therapeutic interventions. Particular BPSD can be observed (long) before the clinical dementia diagnosis and could therefore serve as early indicators of those at risk, and provide a new, non-invasive way to monitor, or at least give an indication of, the complex progression to dementia in DS. Therefore, this review summarizes and evaluates the rather limited knowledge on BPSD in DS and highlights its importance and potential for daily clinical practice. PMID:26343344

  17. Alzheimer's disease biomarkers as outcome measures for clinical trials in MCI

    Science.gov (United States)

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

    2014-01-01

    Background Aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Methods MRI, FDG-PET markers, and ADAS-COG were compared in terms of effect size and statistical power over different followup periods in two MCI groups, selected from ADNI dataset based on CSF (abnormal CSF Aβ1-42 concentration - ABETA+) or MRI evidence of Alzheimer's Disease (AD) (positivity to hippocampal atrophy - HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Results Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. Conclusions These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials. PMID:25437302

  18. Selective vulnerability in neurodegeneration: insights from clinical variants of Alzheimer's disease.

    Science.gov (United States)

    Mattsson, Niklas; Schott, Jonathan M; Hardy, John; Turner, Martin R; Zetterberg, Henrik

    2016-09-01

    Selective vulnerability in the nervous system refers to the fact that subpopulations of neurons in different brain systems may be more or less prone to abnormal function or death in response to specific types of pathological states or injury. The concept has been used extensively as a potential way of explaining differences in degeneration patterns and the clinical presentation of different neurodegenerative diseases. Yet the increasing complexity of molecular histopathology at the cellular level in neurodegenerative disorders frequently appears at odds with phenotyping based on clinically-directed, macroscopic regional brain involvement. While cross-disease comparisons can provide insights into the differential vulnerability of networks and neuronal populations, we focus here on what is known about selective vulnerability-related factors that might explain the differential phenotypic expressions of the same disease-in this case, typical and atypical forms of Alzheimer's disease. Whereas considerable progress has been made in this area, much is yet to be elucidated; further studies comparing different phenotypic variants aimed at identifying both vulnerability and resilience factors may provide valuable insights into disease pathogenesis, and suggest novel targets for therapy. PMID:26746185

  19. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

    2016-02-14

    Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics. PMID:26652155

  20. Association of the apolipoprotein E {epsilon}4 allele with clinical subtypes of autopsy-confirmed Alzheimer`s Disease

    Energy Technology Data Exchange (ETDEWEB)

    Zubenko, G.S.; Stiffler, S.; Kopp, U. [Univ. of Pittsburgh School of Medicine, PA (United States)] [and others

    1994-09-15

    Consistent with previous reports, we observed a significant association of the APOE {epsilon}4 allele with Alzheimer`s Disease (AD) in a series of 91 autopsy-confirmed cases. The {epsilon}4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 {+-} 0.07), although the {epsilon}4 allele frequency in the AD cases with a negative family history (0.38 {+-} 0.05) remained significantly greater than that for the non-AD control group (0.13 {+-} 0.03). A similar increase in {epsilon}4 allele frequency (0.54 {+-} 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.35 {+-} 0.04). Contrary to previous reports, no effect of the dosage of the {epsilon}4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of {epsilon}4 and atherosclerosis, the {epsilon}4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of {epsilon}4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the {epsilon}4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an {epsilon}4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the {epsilon}4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE {epsilon}4 allele. 22 refs., 2 figs., 5 tabs.

  1. Alzheimer's Project

    Medline Plus

    Full Text Available ... voluntary health organization in Alzheimer's care, support and research, the Alzheimer's Association has been an active partner in "THE ALZHEIMER'S PROJECT," ... (48 minutes) "Momentum ...

  2. Alzheimer´s disease: a clinical-practice-oriented review

    Directory of Open Access Journals (Sweden)

    Luísa eAlves

    2012-04-01

    Full Text Available Investigation in the field of Alzheimer´s disease (AD, the commonest cause of dementia, has been very active in recent years and it may be difficult for the clinician to keep up with all the innovations and to be aware of the implications they have in clinical practice. The authors, thus, reviewed recent literature on the theme in order to provide the clinician with an updated overview, intended to support decision-making on aspects of diagnosis and management. This article begins to focus on the concept of AD and on its pathogenesis. Afterwards, epidemiology and non-genetic risk factors are approached. Genetics, including genetic risk factors and guidelines for genetic testing, are mentioned next. Recommendations for diagnosis of AD, including recently proposed criteria, are then reviewed. Data on the variants of AD is presented. First approach to the patient is dealt with next, followed by neuropsychological evaluation. Biomarkers, namely MRI, SPECT, FDG PET, PiB PET, CSF tau and Aβ analysis, as well as available data on their diagnostic accuracy, are also discussed. Factors predicting rate of disease progression are briefly mentioned. Finally, non-pharmacological and pharmacological treatments, including established and emerging drugs, are addressed.

  3. Chronic unremitting headache associated with Lyme disease-like illness

    Directory of Open Access Journals (Sweden)

    Pedro Andre Kowacs

    2013-07-01

    Full Text Available The Brazilian Lyme-disease-like illness (BLDLI or Baggio-Yoshinari syndrome is a unique zoonosis found in Brazil. It reproduces all the clinical symptoms of Lyme disease except for the high frequencies of relapse and the presence of autoimmune manifestations. Two cases of borreliosis manifesting with unremitting headache, which is a symptom associated with late-stage BLDLI, were presented. Clinical, therapeutic, and prognostic aspects of the BLDLI and its associated headaches were showed and discussed in this article. BLDLI diagnosis requires additional attention by physicians, since the disease has a tendency to progress to the late, recurrent stage or the chronic form, and the associated headache can be confused with chronic primary headache or with analgesic-overuse one. Special attention should be paid to patients with headaches who have traveled to endemic areas.

  4. Alzheimer's Project

    Medline Plus

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

  5. Alzheimer's Project

    Medline Plus

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

  6. Alzheimer's Project

    Medline Plus

    Full Text Available ... leading us to find a cure. This multi-platform series reveals groundbreaking Alzheimer's discoveries and the effects ... dementia What is Alzheimer's Stages of Alzheimer's Treatments Virtual Library Interactive Brain Tour Learn how Alzheimer's affects ...

  7. 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 ...

  8. The PSEN1 I143T mutation in a Swedish family with Alzheimer disease: Clinical report and quantification of Aβ in different brain regions

    OpenAIRE

    Graff, Caroline; Keller, Lina; Welander, Hedvig; Chiang, Huei-Hsin; Tjernberg, Lars O.; Nennesmo, Inger; Wallin, Åsa K

    2010-01-01

    Abstract Early onset dominantly-inherited forms of Alzheimer disease are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in APP, PSEN1 and PSEN2, alter the APP processing and lead to an increased amyloid ?-peptide (A?) 42/40 ratio. This, together with other studies on the pathogenic mechanisms, show that A?42 is a major player in the etiology of Alzheimer disease. Here we present a clinical and neuropathologic...

  9. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

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

  10. Cerebrospinal fluid biomarkers in Alzheimer's and Parkinson's diseases-From pathophysiology to clinical practice.

    Science.gov (United States)

    Blennow, Kaj; Biscetti, Leonardo; Eusebi, Paolo; Parnetti, Lucilla

    2016-06-01

    This review provides an update on the role, development, and validation of CSF biomarkers in the diagnosis and prognosis of Alzheimer's disease and PD. Some recent developments on novel biomarkers are also discussed. We also give an overview of methodological/technical factors still hampering the global validation and standardization of CSF Alzheimer's disease and PD biomarkers. CSF biomarkers have the potential to improve the diagnostic accuracy at the early stages not only for Alzheimer's disease but also for PD. This step is essential in view of the availability of disease-modifying treatments. Our vision for the future is that analyzing biomarker panels on a minute amount of CSF could provide important information on the whole spectrum of the molecular pathogenic events characterizing these neurodegenerative disorders. CSF core biomarkers have already been included in the diagnostic criteria for Alzheimer's disease, and they are also under consideration as tools to monitor the effects of disease-modifying drugs. With respect to PD, their potential for improving diagnostic accuracy in early diagnosis is under intense research, resembling the same path followed for Alzheimer's disease. © 2016 International Parkinson and Movement Disorder Society. PMID:27145480

  11. Sleep continuity scale in Alzheimer's disease (SCADS): application in daily clinical practice in an Italian center for dementia.

    Science.gov (United States)

    Manni, R; Sinforiani, E; Terzaghi, M; Rezzani, C; Zucchella, C

    2015-03-01

    Sleep disorders can occur in many neurodegenerative disorders; in a previous paper we constructed a scale investigating sleep discontinuity/fragmentation with the aim to obtain a rapidly and easily administered tool suitable for early identification and longitudinal monitoring of sleep disturbances in Alzheimer's disease (AD). We introduced this instrument in the daily clinical practice in a center for dementia; here we present the results of our experience. Two hundred and sixteen AD outpatients referred to the Alzheimer's Disease Assessment Unit at the IRCCS C. Mondino National Neurological Institute, Pavia, Italy, in the period October 2012 to March 2014 were administered the scale. The questionnaire global score was correlated with measures of cognitive, functional and behavioral impairment; a significant association was found with Mini-Mental State (p = 0.005), Activities of Daily Living (p = 0.01), Neuropsychiatric Inventory (p = 0.01) and Clinical Dementia Rating (p = 0.0005). The present data indicate that the previously validated questionnaire proves to be a suitable, rapid and easy to use tool in investigating sleep quality in AD in daily clinical practice. An early identification and longitudinal monitoring of sleep disturbances in AD may improve pharmacological and non-pharmacological interventions. PMID:25294429

  12. Renovating Alzheimer's: "Constructive" Reflections on the New Clinical and Research Diagnostic Guidelines

    Science.gov (United States)

    George, Daniel R.; Qualls, Sara H.; Camp, Cameron J.; Whitehouse, Peter J.

    2013-01-01

    The development of disease concepts for conditions such as Alzheimer's disease (AD) is an ongoing social process that evolves over time. The biomedical paradigm about AD that has informed our culture's understanding of brain aging for the past several decades is currently undergoing a major and timely renovation in the early 21st century. This…

  13. Review of Information and Communication Technology Devices for Monitoring Functional and Cognitive Decline in Alzheimer's Disease Clinical Trials

    Directory of Open Access Journals (Sweden)

    Jagan A. Pillai

    2015-01-01

    Full Text Available Detecting and monitoring early cognitive impairment in Alzheimer's disease (AD is a significant need in the field of AD therapeutics. Successful AD clinical trial designs have to overcome challenges related to the subtle nature of early cognitive changes. Continuous unobtrusive assessments using Information and Communication Technology (ICT devices to capture markers of intra-individual change over time to assess cognitive and functional disability therefore offers significant benefits. We review the literature and provide an overview on randomized clinical trials in AD that use intelligent systems to monitor functional decline, as well as strengths, weaknesses, and future directions for the use of ICTs in a new generation of AD clinical trials.

  14. Alzheimer's Project

    Medline Plus

    Full Text Available ... Web site . Become an Alzheimer's champion. Help support vital research and services. "THE ALZHEIMER'S PROJECT" is a ... Your Local Chapter Get the facts 10 warning signs What is dementia What is Alzheimer's Stages of ...

  15. Alzheimer's Myths

    Science.gov (United States)

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

  16. Alzheimer disease

    Science.gov (United States)

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

  17. Alzheimer's Project

    Medline Plus

    Full Text Available ... As the leading voluntary health organization in Alzheimer's care, support and research, the Alzheimer's Association has been ... Alzheimer's I am a caregiver I am a care professional I am a physician I am a ...

  18. Alzheimer's Project

    Medline Plus

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

  19. Alzheimer's Project

    Medline Plus

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

  20. Alzheimer disease

    Science.gov (United States)

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

  1. 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…

  2. Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease

    OpenAIRE

    Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih

    2015-01-01

    Abstract Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to f...

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

    OpenAIRE

    Lindau, Maria

    2002-01-01

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

  4. Anti-microRNAs as Novel Therapeutic Agents in the Clinical Management of Alzheimer's Disease

    OpenAIRE

    Zhao, Yuhai; Alexandrov, Peter N.; Lukiw, Walter J.

    2016-01-01

    Overview- One hundred and ten years since its first description Alzheimer's disease (AD) still retains its prominent status: (i) as the industrialized world's number one cause of age-related intellectual impairment and cognitive decline; (ii) as this country's most rapidly expanding socioeconomic and healthcare concern; and (iii) as an insidious, progressive and lethal neurological disorder of the human central nervous system (CNS) for which there is currently no adequate treatment or cure (A...

  5. Anti-microRNAs as Novel Therapeutic Agents in the Clinical Management of Alzheimer's Disease.

    Science.gov (United States)

    Zhao, Yuhai; Alexandrov, Peter N; Lukiw, Walter J

    2016-01-01

    Overview- One hundred and ten years since its first description Alzheimer's disease (AD) still retains its prominent status: (i) as the industrialized world's number one cause of age-related intellectual impairment and cognitive decline; (ii) as this country's most rapidly expanding socioeconomic and healthcare concern; and (iii) as an insidious, progressive and lethal neurological disorder of the human central nervous system (CNS) for which there is currently no adequate treatment or cure (Alzheimer, 1991; Alzheimer et al., 1991, 1995) [https://www.alz.org/facts/downloads/facts_figures_2015.pdf (2015)]. The concept of small non-coding RNAs (ncRNAs) as being involved in the etiopathogenesis of AD and age-related human neurodegenerative disease was first proposed about 25 years ago, however it was not until 2007 that specific microRNA (miRNA) abundance, speciation and localization to the hippocampal CA1 region (an anatomical area of the human CNS specifically targeted by the AD process) was shown to strongly associate with AD-type change when compared to age-matched controls (Lukiw et al., 1992; Lukiw, 2007; Schipper et al., 2007; Cogswell et al., 2008; Guerreiro et al., 2012). Currently about 400 reports address the potential link between disruptions in miRNA signaling and the development of various features associated with AD neuropathology (http://www.ncbi.nlm.nih.gov/pubmed/?term=micro+RNA+alzheimer's+disease). In this "Perspectives" paper we will highlight some of the most recent literature on anti-miRNA (AM; antagomir) therapeutic strategies and some very recent technological advances in the analysis and characterization of defective miRNA signaling pathways in AD compared to neurologically normal age-matched controls. PMID:26941600

  6. Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jones Roy

    2011-10-01

    Full Text Available Abstract Background Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here a successful example of this type of collaboration in the field of dementia. Methods The Donepezil Data Repository comprised 18 randomised, controlled trials conducted between 1991 and 2005. The project team at Pfizer determined that the data mining process should be guided by a diverse group of leading Alzheimer's disease clinical researchers called the "Expert Working Group." After development of a list of potential faculty members, invitations were extended and a group of seven members was assembled. The Working Group met regularly with Eisai/Pfizer clinicians and statisticians to discuss the data, identify issues that were currently of interest in the academic and clinical communities that might lend themselves to investigation using these data, and note gaps in understanding or knowledge of Alzheimer's disease that these data could address. Leadership was provided by the Pfizer Clinical Development team leader; Working Group members rotated responsibility for being lead and co-lead for each investigation and resultant publication. Results Six manuscripts, each published in a leading subspecialty journal, resulted from the group's work. Another project resulted in poster presentations at international congresses and two were cancelled due to resource constraints. Conclusions The experience represents a particular approach to

  7. Alzheimer's Project

    Medline Plus

    Full Text Available ... Chicago National Alzheimer's Gala A Night at Sardi's Alzheimer's Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project ... help us change the way Americans thinks about Alzheimer's disease. Tell your family and friends. Post info on ...

  8. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification.

    Directory of Open Access Journals (Sweden)

    Igor O Korolev

    Full Text Available Individuals with mild cognitive impairment (MCI have a substantially increased risk of developing dementia due to Alzheimer's disease (AD. In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level.Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139 and those who did not (n = 120 during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework.Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87. Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex. Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions.We developed an accurate prognostic model for predicting MCI-to-dementia progression

  9. The contribution of single photon emission computed tomography in the clinical assessment of Alzheimer type dementia; Apport de la tomographie d'emission monophonique cerebrale dans l'evaluation des demences de type Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Boudousq, V.; Collombier, L.; Kotzki, P.O. [Centre Hospitalier Universitaire de Nimes, 30 (France)

    1999-12-01

    Interest of brain single-photon emission computed tomography to support clinical diagnosis of Alzheimer-type dementia is now established. Numerous studies have reported a decreased perfusion in the association cortex of the parietal lobe and the posterior temporal regions. In patients with mild cognitive complaints, the presence of focal hypoperfusion may increase substantially the probability of the disease. In addition, emission tomography emerges as a helpful tool in situation in which there is diagnostic doubt. In this case, the presence of temporo-parietal perfusion deficit associated with hippocampal atrophy on MRI or X-ray computed tomography contributes to diagnostic accuracy. However, some studies suggest that emission tomography may be useful for preclinical prediction of Alzheimer's disease and to predict cognitive decline. (author)

  10. Reduced acetylcholine synthesis in Alzheimer's disease is a clinically relevant change

    International Nuclear Information System (INIS)

    This paper presents a study of patients in the presenium. Psychological assessment was carried out to provide measures of relative severity of dementia, with which pathological and chemical indices of impairment could be compared. Fresh cortical biopsy tissue permitted the assay of ChAT activity, and also the determination of acetylcholine synthesis in a preparation enriched in cortical synaptosomes. Additionally, choline uptake has been measured for comparison. Nuerosurgical samples from all patients were handled and processed for measuring acetylcholine synthesis by incorporation of U-14C-glucoase into C 14-acetylcholine in neocortical tissue prisms. Cortical sections from most of the patients were found on light microscopy to contain the characteristic changes of Alzheimer's disease

  11. Alzheimer's Project

    Science.gov (United States)

    ... state Home > News & Events > Upcoming Events > HBO Alzheimer’s Project In the News Walk to End Alzheimer's Upcoming ... Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project MAKE A DONATION Your gift will help us ...

  12. Alzheimer's Project

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    Full Text Available ... THE ALZHEIMER'S PROJECT," providing expert insight and leading community engagement. Talk about the films on our message board . ... support vital research and services. "THE ALZHEIMER'S PROJECT" is a presentation of HBO ...

  13. Alzheimer's: Glossary

    Science.gov (United States)

    ... Stress Caregiver Depression Relationship Changes Grief & Loss as Alzheimer's Progresses Start Here What You Need to Know ... Weekly E-News Stay up-to-date on Alzheimer's treatments and care. First name: Last name: Email: * ...

  14. Understanding Alzheimer's

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Understanding Alzheimer's Past Issues / Fall 2007 Table of Contents For ... and brain scans. No treatment so far stops Alzheimer's. However, for some in the disease's early and ...

  15. Alzheimer's Project

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    Full Text Available ... your family and friends. Post info on your Web site . Become an Alzheimer's champion. Help support vital ... Become an advocate About the Alzheimer's Association | Careers | Security & Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters ...

  16. Alzheimer's Project

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    Full Text Available ... Nonfiction Program. - Emmys.com As the leading voluntary health organization in Alzheimer's care, support and research, the ... Institute on Aging at the National Institutes of Health in association with the Alzheimer's Association, The Fidelity ® ...

  17. Alzheimer's Project

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    Full Text Available ... to kids. $9.99 More resources for kids Learn how Maria Shriver is raising awareness Get help ... of Alzheimer's Treatments Virtual Library Interactive Brain Tour Learn how Alzheimer's affects the brain Join us on... ...

  18. Alzheimer's Project

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    Full Text Available ... films on our message board . Watch films free online now "The Memory Loss Tapes" (85 minutes) "Grandpa, ... an advocate About the Alzheimer's Association | Careers | Security & Privacy Policy | Copyrights & Reprints | Contact Us National Headquarters Alzheimer's ...

  19. Alzheimer's Project

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    Full Text Available ... 14, 2009 "The Alzheimer's Project" wins two Creative Arts Emmys Two installments of the multi-part HBO ... from the Alzheimer's Association and others, won Creative Arts Emmy awards. "The Memory Loss Tapes" was honored ...

  20. Alzheimer's Project

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    Full Text Available ... A DONATION Your gift will help us accelerate research and move closer to a cure. HBO Alzheimer’s ... voluntary health organization in Alzheimer's care, support and research, the Alzheimer's Association has been an active partner ...

  1. Alzheimer's Project

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

  2. Alzheimer's Project

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    Full Text Available ... Momentum in Science, Part 2" (70 minutes) Be a part of something big. HBO's "THE ALZHEIMER'S PROJECT" ... vital research and services. "THE ALZHEIMER'S PROJECT" is a presentation of HBO Documentary Films and the National ...

  3. Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer's disease.

    Science.gov (United States)

    Rieckmann, Anna; Van Dijk, Koene R A; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L; Hedden, Trey

    2016-06-01

    Prior studies have identified white matter abnormalities in Alzheimer's disease (AD). Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity. Here, 108 normal older adults (age, 66-87) with assessments of apolipoprotein e4 (APOE4) genotype and assessment of amyloid burden by positron emission tomography underwent diffusion tensor imaging scans for measuring white matter integrity at 2 time points, on average 2.6 years apart. Linear mixed-effects models showed that amyloid burden at baseline was associated with steeper decline in fractional anisotropy in the parahippocampal cingulum (p < 0.05). This association was not significant between baseline measures suggesting that longitudinal analyses can provide novel insights that are not detectable in cross-sectional designs. Amyloid-related changes in hippocampus volume did not explain the association between amyloid burden and change in fractional anisotropy. The results suggest that accumulation of cortical amyloid and white matter changes in parahippocampal cingulum are not independent processes in individuals at increased risk for AD. PMID:27143434

  4. Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.

    Science.gov (United States)

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Rawat, Chitra; Kushwaha, Suman; Agarwal, Rachna; Taneja, Vibha; Kukreti, Ritushree

    2016-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD. PMID:26351077

  5. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... what to consider in patients with a negative Huntington's disease gene test. Nat Clin Pract Neurol. 2007 Sep;3( ... San C, Bellance R, Brice A, Durr A. Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. Brain. 2003 Jul;126(Pt 7):1599-603. ...

  6. Alzheimer's Project

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    Full Text Available ... Alzheimer's Gala A Night at Sardi's Alzheimer's Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project MAKE ... for kids Learn how Maria Shriver is raising awareness '; jQuery('#luminateApi').hide(); jQuery('#otherLinks').show(); jQuery('#TRByZip'). ...

  7. Alzheimer's Project

    Medline Plus

    Full Text Available ... Program. - Emmys.com As the leading voluntary health organization in Alzheimer's care, support and research, the Alzheimer's ... is a not-for-profit 501(c)(3) organization. Copyright © 2016 Alzheimer's Association ® . All rights reserved. Our ...

  8. Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

    Science.gov (United States)

    Sevigny, Jeff; Suhy, Joyce; Chiao, Ping; Chen, Tianle; Klein, Gregory; Purcell, Derk; Oh, Joonmi; Verma, Ajay; Sampat, Mehul; Barakos, Jerome

    2016-01-01

    Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE ε4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials. PMID:26885819

  9. Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer's disease Ibero-American cohort

    OpenAIRE

    Jin, Sheng Chih; Pastor, Pau; Cooper, Breanna; Cervantes, Sebastian; Benitez, Bruno. A; Razquin, Cristina; Goate, Alison; ,; Cruchaga, Carlos

    2012-01-01

    Introduction Some familial Alzheimer's disease (AD) cases are caused by rare and highly-penetrant mutations in APP, PSEN1, and PSEN2. Mutations in GRN and MAPT, two genes associated with frontotemporal dementia (FTD), have been found in clinically diagnosed AD cases. Due to the dramatic developments in next-generation sequencing (NGS), high-throughput sequencing of targeted genomic regions of the human genome in many individuals in a single run is now cheap and feasible. Recent findings favor...

  10. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  11. Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate alzheimer's disease

    DEFF Research Database (Denmark)

    Wilkinson, David; Schindler, Rachel; Schwam, Elias;

    2009-01-01

    donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician's Interview-Based Impression of Change...... plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of...... was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared...

  12. Beyond acetylcholinesterase inhibitors for treating Alzheimer's disease: α7-nAChR agonists in human clinical trials.

    Science.gov (United States)

    Russo, Patrizia; Del Bufalo, Alessandra; Frustaci, Alessandra; Fini, Massimo; Cesario, Alfredo

    2014-01-01

    The neuronal nicotinic alpha7-acetylcholine receptor (α7-nAChR) is a promising and attractive drug target for improving cognitive deficits in neuropsychiatric and neurological disorders such as Alzheimer's disease (AD). α7-nAChR belongs to the family of ligand gated ion channels. α7-nAChR is expressed in key brain regions (e.g. pre- and frontal cortex, hippocampus). It is involved in essential cognitive functions such as memory, thinking, comprehension, learning capacity, calculation, orientation, language, and judgment. α7-nAChR binds to amyloid peptide (Aβ) inducing either receptor activation or inhibition in an Aβ concentration-dependent mode. Aβ oligomers induce τ phosphorylation via α7-nAChR activation. α7-nAChR agonists and/or α7-nAChR positive allosteric modulators may be useful in AD therapy. The current review enlightens: (i) α7-nAChR neurobiology, (ii) α7-nAChR role in cognition and (iii) in AD, and (iv) the clinical status of the most promising molecules for the treatment of cognitive dysfunction in AD. PMID:24641224

  13. A novel approach of groupwise fMRI-guided tractography allowing to characterize the clinical evolution of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Maria Giulia Preti

    Full Text Available Guiding diffusion tract-based anatomy by functional magnetic resonance imaging (fMRI, we aim to investigate the relationship between structural connectivity and functional activity in the human brain. To this purpose, we introduced a novel groupwise fMRI-guided tractographic approach, that was applied on a population ranging between prodromic and moderate stages of Alzheimer's disease (AD. The study comprised of 15 subjects affected by amnestic mild cognitive impairment (aMCI, 14 diagnosed with AD and 14 elderly healthy adults who were used as controls. By creating representative (ensemble functionally guided tracts within each group of participants, our methodology highlighted the white matter fiber connections involved in verbal fluency functions for a specific population, and hypothesized on brain compensation mechanisms that potentially counteract or reduce cognitive impairment symptoms in prodromic AD. Our hope is that this fMRI-guided tractographic approach could have potential impact in various clinical studies, while investigating white/gray matter connectivity, in both health and disease.

  14. Measurement of Neuropsychiatric Symptoms in Clinical Trials Targeting Alzheimer's Disease and Related Disorders

    OpenAIRE

    Emmanuel Mulin; Renaud David; Patrick Mallea; Robert, Philippe H.

    2010-01-01

    Behavioral and psychological symptoms (BPSD) are now known to be frequently associated to cognitive and functional decline in Alzheimer‘s disease and related disorders. They are present since the early stages of the disease and have negative impact on the disease process. BPSD assessment is crucial in clinical practice and also in future clinical trials targeting disease-modifying therapies for dementia. In this article, we will first review current assessment tools for BPSD, mainly global an...

  15. Measurement of Neuropsychiatric Symptoms in Clinical Trials Targeting Alzheimer's Disease and Related Disorders

    Directory of Open Access Journals (Sweden)

    Emmanuel Mulin

    2010-07-01

    Full Text Available Behavioral and psychological symptoms (BPSD are now known to be frequently associated to cognitive and functional decline in Alzheimer‘s disease and related disorders. They are present since the early stages of the disease and have negative impact on the disease process. BPSD assessment is crucial in clinical practice and also in future clinical trials targeting disease-modifying therapies for dementia. In this article, we will first review current assessment tools for BPSD, mainly global and domain-specific scales, and new assessment methods, currently available or in development, including new scales, diagnostic criteria and new technologies such as ambulatory actigraphy.

  16. About Alzheimer's Disease: Symptoms

    Science.gov (United States)

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

  17. Clinical significance of determination of plasma Leptin and serum Hcy, S100B and NSE levels in patients with alzheimer disease

    International Nuclear Information System (INIS)

    To explore the clinical significance of changes of plasma leptin and serun Hcy, S100B and NSE levels in patients with Alzheimer Disease (AD). The plasma leptin and serum NSE levels in 32 AD patients and 30 controls were determined by using RIA, and the serum Hcy and S100B levels were measured by using CLIA. The results showed that the plasma leptin and serun Hcy, S100B and NSE levels in AD patients were significantly higher than these in controls (P<0.01). The plasma leptin levels in AD patients was mutually positively correlated with serum Hcy, S100B and NSE levels (r=0.5982, 0.4762, 0.6014, P<0.01). The detection of plasma leptin and serum Hcy, S100B and NSE levels may be helpful for the prediction of treatment efficiency in patients with Alzheimer disease. (authors)

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

    Science.gov (United States)

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

    2016-01-01

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

  19. The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

    OpenAIRE

    Ames David; Flicker Leon; Almeida Osvaldo P; Cox Kay L; Cyarto Elizabeth V; Byrne Gerard; Hill Keith D; Beer Christopher D; LoGiudice Dina; Appadurai Kana; Irish Muireann; Renehan Emma; Lautenschlager Nicola T

    2010-01-01

    Abstract Background Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of...

  20. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Mateus Rocha de Paula

    Full Text Available BACKGROUND: In November 2007 a study published in Nature Medicine proposed a simple test based on the abundance of 18 proteins in blood to predict the onset of clinical symptoms of Alzheimer's Disease (AD two to six years before these symptoms manifest. Later, another study, published in PLoS ONE, showed that only five proteins (IL-1, IL-3, EGF, TNF- and G-CSF have overall better prediction accuracy. These classifiers are based on the abundance of 120 proteins. Such values were standardised by a Z-score transformation, which means that their values are relative to the average of all others. METHODOLOGY: The original datasets from the Nature Medicine paper are further studied using methods from combinatorial optimisation and Information Theory. We expand the original dataset by also including all pair-wise differences of z-score values of the original dataset ("metafeatures". Using an exact algorithm to solve the resulting Feature Set problem, used to tackle the feature selection problem, we found signatures that contain either only features, metafeatures or both, and evaluated their predictive performance on the independent test set. CONCLUSIONS: It was possible to show that a specific pattern of cell signalling imbalance in blood plasma has valuable information to distinguish between NDC and AD samples. The obtained signatures were able to predict AD in patients that already had a Mild Cognitive Impairment (MCI with up to 84% of sensitivity, while maintaining also a strong prediction accuracy of 90% on a independent dataset with Non Demented Controls (NDC and AD samples. The novel biomarkers uncovered with this method now confirms ANG-2, IL-11, PDGF-BB, CCL15/MIP-1; and supports the joint measurement of other signalling proteins not previously discussed: GM-CSF, NT-3, IGFBP-2 and VEGF-B.

  1. Alzheimer's Project

    Medline Plus

    Full Text Available ... state Home > News & Events > Upcoming Events > HBO Alzheimer’s Project In the News Walk to End Alzheimer's Upcoming ... Disease Awareness Month World Alzheimer's Month HBO Alzheimer’s Project MAKE A DONATION Your gift will help us ...

  2. Alzheimer's Project

    Medline Plus

    Full Text Available ... 2" (70 minutes) Be a part of something big. HBO's "THE ALZHEIMER'S PROJECT" will expose the Alzheimer's ... show(); jQuery('#TRByZip').html(teamRaisersListHTML); teamRaisersListHTML = ''; } } else { if (data && data.getTeamraisersResponse) { var teamraisers = luminateExtend.utils.ensureArray(data. ...

  3. A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.

    Science.gov (United States)

    Shea, Yat-Fung; Chu, Leung-Wing; Chan, Angel On-Kei; Ha, Joyce; Li, Yan; Song, You-Qiang

    2016-02-01

    There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p personality change (p = 0.01) but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites. PMID:26337232

  4. The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of Aβ in different brain regions

    OpenAIRE

    Keller, Lina; Welander, Hedvig; Chiang, Huei-Hsin; Tjernberg, Lars O.; Nennesmo, Inger; Wallin, Åsa K; Graff, Caroline

    2010-01-01

    Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid β-peptide (Aβ) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that Aβ42 is a major player in the etiology of AD. Here, we present a clinical and neu...

  5. Are Clinical Diagnoses of Alzheimer's Disease and Other Dementias Affected by Education and Self-Reported Race?

    Science.gov (United States)

    Teresi, Jeanne A.; Grober, Ellen; Eimicke, Joseph P.; Ehrlich, Amy R.

    2012-01-01

    A randomized controlled trial examined whether the diagnostic process for Alzheimer's disease and other dementias may be influenced by knowledge of the patient's education and/or self-reported race. Four conditions were implemented: diagnostic team knows (a) race and education, (b) education only, (c) race only, or (d) neither. Diagnosis and…

  6. The neuropsychiatric manifestations of Huntington's disease-like 2.

    Science.gov (United States)

    Fischer, Christopher A; Licht, Eliot A; Mendez, Mario F

    2012-01-01

    Huntington's disease-like 2 (HDL2) is a rare neuropsychiatric disorder that resembles HD but results from a distinct mutation. The authors present a patient with HDL2, hospitalized for psychiatric management, and they review the neuropsychiatric manifestations of this disorder. Depression, irritability/aggression, and frontal lobe personality changes are common presentations of HDL2 and are comparable to classic HD. Patients with HDL2 may differ from those with HD in having a lower incidence of obsessive-compulsive acts, known suicides, antisocial acts, and changes in sexuality. Clinicians should be aware of the psychiatric presentations of this disorder, when to obtain genetic testing, and how to manage problematic behaviors. PMID:23224457

  7. Study of the clinical and the neuroradiological findings in multi-infarct dementia and Alzheimer type dementia

    Energy Technology Data Exchange (ETDEWEB)

    Endo, Riuko (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    In forty patients with dementia, a comparison of the clinical and the neuroradiological findings between 15 Alzheimer type dementia (ATD) and 21 multi-infarct dementia (MID) were made. MID had significantly (p<0.01) higher Hachinski's Ischemic Score (HIS) (mean +-S.D., 9.7+-1.8) compared with ATD (3.6+-1.5). The HIS was a useful diagnostic aid in differential diagnosis between the two groups. MID significantly (p<0.01) had cerebrovascular risk factors such as hypertension, diabetes mellitus and increase of platelet aggregation. The morphometric analysis of the ratios of the ventricular dilatation, the cortical atrophy, and the white matter changes was performed on the CT scan and the magnetic resonance imaging. This was the first time the method of having the cortical atrophy analyzed by the ratio of the area of the sylvian sulci and the area of the whole brain had been used. It was found that the degrees of the ventricular dilatation, the cortical atrophy, and the white matter changes were more increased in MID than in ATD (p<0.01{similar to}0.05). In ATD, there was a positive correlation between Hasegawa's Dementia Scale and both the ratios of the ventricular dilatation, and the cortical atrophy (r=-0.62, p<0.05, r=-0.63, p<0.05, respectively). Also a comparative study between MID and 9 patients with multiple infarction, without dementia (MI). MID had the mean infarct numbers of 6.5+-2.5, and MI had 4.1+-2.2. The white matter changes were more increased in MID than MI (p<0.05). The incidence of the dementia was significantly higher in cases with left lenticular nucleus (p<0.01) or main lesions of the white matter in the left frontal lobe (p<0.05), and in cases with bilateral lenticular nucleus (p<0.01), compared to cases without lesions. (J.P.N.).

  8. A study of the clinical and the neuroradiological findings in multi-infarct dementia and Alzheimer type dementia

    International Nuclear Information System (INIS)

    In forty patients with dementia, a comparison of the clinical and the neuroradiological findings between 15 Alzheimer type dementia (ATD) and 21 multi-infarct dementia (MID) were made. MID had significantly (p<0.01) higher Hachinski's Ischemic Score (HIS) (mean ±S.D., 9.7±1.8) compared with ATD (3.6±1.5). The HIS was a useful diagnostic aid in differential diagnosis between the two groups. MID significantly (p<0.01) had cerebrovascular risk factors such as hypertension, diabetes mellitus and increase of platelet aggregation. The morphometric analysis of the ratios of the ventricular dilatation, the cortical atrophy, and the white matter changes was performed on the CT scan and the magnetic resonance imaging. This was the first time the method of having the cortical atrophy analyzed by the ratio of the area of the sylvian sulci and the area of the whole brain had been used. It was found that the degrees of the ventricular dilatation, the cortical atrophy, and the white matter changes were more increased in MID than in ATD (p<0.01∼0.05). In ATD, there was a positive correlation between Hasegawa's Dementia Scale and both the ratios of the ventricular dilatation, and the cortical atrophy (r=-0.62, p<0.05, r=-0.63, p<0.05, respectively). Also a comparative study between MID and 9 patients with multiple infarction, without dementia (MI). MID had the mean infarct numbers of 6.5±2.5, and MI had 4.1±2.2. The white matter changes were more increased in MID than MI (p<0.05). The incidence of the dementia was significantly higher in cases with left lenticular nucleus (p<0.01) or main lesions of the white matter in the left frontal lobe (p<0.05), and in cases with bilateral lenticular nucleus (p<0.01), compared to cases without lesions. (J.P.N.)

  9. Increased hippocampal neurogenesis in Alzheimer's disease

    OpenAIRE

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

    2003-01-01

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

  10. Alzheimer's Disease Medications

    Science.gov (United States)

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

  11. Alzheimer's Disease Genetics

    Science.gov (United States)

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

  12. Understanding Alzheimer's Disease

    Science.gov (United States)

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

  13. 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 ...

  14. Alzheimer's Project

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    Full Text Available ... about the films on our message board . Watch films free online now "The Memory Loss Tapes" (85 ... ALZHEIMER'S PROJECT" is a presentation of HBO Documentary Films and the National Institute on Aging at the ...

  15. Alzheimer's Project

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    Full Text Available ... the forces leading us to find a cure. This multi-platform series reveals groundbreaking Alzheimer's discoveries and the effects this debilitating and fatal disease has on those with ...

  16. Alzheimer's Project

    Medline Plus

    Full Text Available ... 272.3900 Find your chapter: search by state Home > News & Events > Upcoming Events > HBO Alzheimer’s Project In the News Walk to End Alzheimer's Upcoming Events AAIC Advocacy Forum Rita ...

  17. Alzheimer's Caregiving

    Science.gov (United States)

    ... version of this page please turn Javascript on. Alzheimer's Caregiving After the Diagnosis Now that your family ... the news with family and friends. Learning About Alzheimer’s Sometimes, you may feel that you don't ...

  18. Alzheimer's Project

    Medline Plus

    Full Text Available ... I Am? with Maria Shriver" won for Outstanding Children's Nonfiction Program. - Emmys.com As the leading voluntary ... Happening to Grandpa? by Maria Shriver Maria Shriver's children's book is about a grandparent with Alzheimer's. A ...

  19. Alzheimer's Project

    Medline Plus

    Full Text Available ... our nation and drive concerned citizens to take action. Here are three ways you can help us change the way ... vital research and services. "THE ALZHEIMER'S PROJECT" is a presentation ...

  20. Alzheimer's Project

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    Full Text Available ... engagement. Talk about the films on our message board . Watch films free online now "The Memory Loss ... Alzheimer's affects the brain Join us on... Message boards Blog Get Involved Make a donation to fight ...

  1. Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

    International Nuclear Information System (INIS)

    Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia.We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions. (orig.)

  2. Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

    Energy Technology Data Exchange (ETDEWEB)

    Teipel, Stefan [University of Rostock, Department of Psychosomatic Medicine, Rostock (Germany); DZNE, German Center for Neurodegenerative Diseases, Rostock (Germany); Alzheimer' s Disease Neuroimaging Initiative (United States); Grothe, Michel J. [DZNE, German Center for Neurodegenerative Diseases, Rostock (Germany); Alzheimer' s Disease Neuroimaging Initiative (United States)

    2016-03-15

    Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia.We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions. (orig.)

  3. Brief Cognitive Screening Battery (BCSB) is a very useful tool for diagnosis of probable mild Alzheimer´s disease in a geriatric clinic.

    Science.gov (United States)

    Fichman-Charchat, Helenice; Miranda, Cristina Vieira; Fernandes, Conceição Santos; Mograbi, Daniel; Oliveira, Rosinda Martins; Novaes, Regina; Aguiar, Daniele

    2016-02-01

    The diagnosis of early signs of Alzheimer's disease (AD) is a major challenge in a heterogeneous population. Objective To investigate the use of the Brief Cognitive Screening Battery (BCSB) for the diagnosis of mild AD in a geriatric outpatient unit of a public hospital in the city of Rio de Janeiro. Method BCSB was administered to 51 elderly adults with a clinical diagnosis of probable AD and 123 older adults without dementia (non-AD). Results AD patients performed worse than non-AD group in all BCSB tests, except Clock Drawing (p = 0.10). The ROC curves and Logistic Regression analysis indicated that delayed recall in the figure memory test was the best predictor, screening mild AD patients with sensibility and specificity superior to 80%. Conclusion The BCSB was accurate in identifying people with AD in a geriatric outpatient clinic at a public hospital, including elderly people with chronic diseases, physical frailty and cognitive impairment. PMID:26690839

  4. 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.

  5. Senile dementia of the Alzheimer type

    Energy Technology Data Exchange (ETDEWEB)

    Hutton, J.T.; Kenny, A.D.

    1985-01-01

    This book contains papers on Alzheimer's Disease. They are divided into several topics. The topic headings are: Clinical Evaluation, Management, and Treatment; Related Clinical Disorders; Epidemiology and Genetics; Basic Science; and National Perspectives and Future Directions.

  6. The immunotherapy of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Weksler Marc E

    2004-11-01

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

  7. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

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

    2014-12-01

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

  8. Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment Preditores clínicos e biológicos da evolução para doença de Alzheimer em pacientes com comprometimento cognitivo leve amnéstico

    Directory of Open Access Journals (Sweden)

    Orestes V. Forlenza

    2010-09-01

    Full Text Available OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010. At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020 and higher concentrations of total TAU (p = 0.030 and phosphorylated TAU (p = 0.010, as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.OBJETIVO: A identificação de preditores da conversão para a doença de Alzheimer em pacientes com comprometimento cognitivo leve é relevante para o manejo clínico e para decidir sobre a prescrição de drogas antidemência. MÉTODO: Estudo longitudinal em coorte de indivíduos idosos com comprometimento cognitivo leve amnéstico e controles saudáveis; estimativa do risco da progressão para doença de Alzheimer nos dois grupos; determinação das vari

  9. Genetics of Alzheimer Disease

    OpenAIRE

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

    2010-01-01

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

  10. Towards a unified vision of copper involvement in Alzheimer's disease: a review connecting basic, experimental, and clinical research.

    Science.gov (United States)

    Pal, Amit; Siotto, Mariacristina; Prasad, Rajendra; Squitti, Rosanna

    2015-01-01

    Copper is an essential micronutrient for physiological cell functioning and central nervous system (CNS) development. Indeed, it is a cofactor of many proteins and enzymes in a number of molecular pathways, including energy generation, oxygen transportation, hematopoiesis, cellular growth and metabolism, and signal transduction. This is because it serves as a catalyst of reduction-oxidation (redox) reactions in these processes. When copper is kept under control, bound to special proteins, it yields key properties. However, when it spirals out of control, it is exchanged among small compounds (it is loosely bound to them), and its redox activity makes it dangerous for cell viability, promoting oxidative stress. Copper homeostasis in the CNS is securely synchronized, and perturbations in brain copper levels are known to underlie the pathoetiology of wide spectrum of common neurodegenerative disorders, including Alzheimer's disease. The main objective of this review is to provide some of the most relevant evidence gleaned from recent studies conducted on animal models and humans, and to discuss the evidence as it pertains to a new concept: Aberrant copper metabolism, which appears to have a genetic basis, is a modifiable risk factor accelerating Alzheimer's disease and initiation/progression of cognitive deficits in a percentage of susceptible persons. PMID:25261447

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

    Science.gov (United States)

    Shinohara, Moeko; Yamada, Masahito

    2015-12-01

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

  12. 99mTc-HMPAO-SPECT in the diagnosis of senile dementia of Alzheimer's type - a study under clinical routine conditions

    International Nuclear Information System (INIS)

    This study was designed to evaluate whether investigations of cerebral blood flow can be a helpful diagnostic tool in the differential diagnosis between (senile) dementia of Alzheimer's type [(S)DAT] and geriatric depression with cognitive impairment. Under clinical routine conditions we performed Single Photon Emission Computed Tomography (SPECT) using 99mTc-Hexamethylpropyleneamine Oxime (HMPAO) in 23 patients with (S)DAT (14 f, 9 m; mean age 68.9 y), 17 patients with geriatric depression (9 f, 8 m; mean age 66.4 y) and 12 age-matched controls (9 f, 3 m; mean age 69.2 y). Semiquantitative analysis (corticocerebellar ratios) of eight different regions of interest (ROI) revealed a significantly ( p 99mTc-HMPAO SPECT is a valuable additional tool in the differential diagnosis of depression and dementia in the elderly. (author)

  13. Alzheimer's Project

    Medline Plus

    Full Text Available ... postal='+postalCode+'&search_distance=100&event_type=Walk 2016&&list_page_size=3&list_page_offset=0& ... not-for-profit 501(c)(3) organization. Copyright © 2016 Alzheimer's Association ® . All rights reserved. Our vision is ...

  14. Alzheimer's Project

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    Full Text Available ... Upcoming Events AAIC Advocacy Forum Rita Hayworth Gala - New York Rita Hayworth Gala - Chicago National Alzheimer's Gala ... function setCookie(c_name, value, expire) { var exdate=new Date(); exdate.setDate(exdate.getDate()+expire); document.cookie = ...

  15. The fitness for the Ageing Brain Study II (FABS II: protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ames David

    2010-12-01

    Full Text Available Abstract Background Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II study is a multicentre randomized controlled clinical trial (RCT aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods. Methods/Design The study will recruit 230 community-dwelling participants diagnosed with Alzheimer's disease. Participants will be randomly allocated to two treatment groups: usual care group or 24-week home-based program consisting of 150 minutes per week of tailored moderate physical activity. The primary outcome measure of the study is cognitive decline as measured by the change from baseline in the total score on the Alzheimer's disease Assessment Scale-Cognitive section. Secondary outcomes of interest include behavioral and psychological symptoms, quality of life, functional level, carer burden and physical function (strength, balance, endurance, physical activity. Primary endpoints will be measured at six and twelve months following the baseline assessment. Discussion This RCT will contribute evidence regarding the potential benefits of a systematic program of physical activity as an affordable and safe intervention for people with Alzheimer's disease. Further, if successful, physical activity in combination with usual care has the potential to alleviate the symptoms of Alzheimer's disease and improve its management and the quality of life of patients and their carers. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12609000755235

  16. Harmonized diagnostic criteria for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  17. Neurotransmitter replacement therapy in Alzheimer's disease.

    OpenAIRE

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

    1994-01-01

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

  18. 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....

  19. Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne;

    2010-01-01

    tract in the respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17 overlaps that of Huntington's disease (HD), hence the use of the term Huntington's disease-like. We screened 89 patients with a...... Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats....... The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington...

  20. Alzheimer's Disease Research Centers

    Science.gov (United States)

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

  1. About Alzheimer's Disease: Diagnosis

    Science.gov (United States)

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

  2. Alzheimer's Disease Information Page

    Science.gov (United States)

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

  3. Mapping ventricular expansion and its clinical correlates in Alzheimer's disease and mild cognitive impairment using multi-atlas fluid image alignment

    Science.gov (United States)

    Chou, Yi-Yu; Lepore, Natasha; Avedissian, Christina; Madsen, Sarah K.; Hua, Xue; Jack, Clifford R., Jr.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2009-02-01

    We developed an automated analysis pipeline to analyze 3D changes in ventricular morphology; it provides a highly sensitive quantitative marker of Alzheimer's disease (AD) progression for MRI studies. In the ADNI image database, we created expert delineations of the ventricles, as parametric surface meshes, in 6 brain MRI scans. These 6 images and their embedded surfaces were fluidly registered to MRI scans of 80 AD patients, 80 individuals with mild cognitive impairment (MCI), and 80 healthy controls. Surface averaging within subjects greatly reduced segmentation error. Surface-based statistical maps revealed powerful correlations between surface morphology at baseline and (1) diagnosis, (2) cognitive performance (MMSE scores), (3) depression, and (4) predicted future decline, over a 1 year interval, in 3 standard clinical scores (MMSE, global and sum-of-boxes CDR). We used a false discovery rate method (FDR) method based on cumulative probability plots to find that 40 subjects were sufficient to discriminate AD from normal groups. 60 and 119 subjects, respectively, were required to correlate ventricular enlargement with MMSE and clinical depression. Surface-based FDR, along with multi-atlas fluid registration to reduce segmentation error, will allow researchers to (1) estimate sample sizes with adequate power to detect groups differences, and (2) compare the power of mapping methods head-to-head, optimizing cost-effectiveness for future clinical trials.

  4. Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

    DEFF Research Database (Denmark)

    Jones, Roy; Wilkinson, David; Lopez, Oscar L; Cummings, Jeffrey; Waldemar, Gunhild; Zhang, Richard; Mackell, Joan; Gauthier, Serge

    2011-01-01

    Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical ...

  5. 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.

  6. Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

    DEFF Research Database (Denmark)

    Jones, Roy; Wilkinson, David; Lopez, Oscar L;

    2011-01-01

    Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical...... community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here a...

  7. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy.

  8. [Immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

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

  9. A doença de Alzheimer na visão de familiares de pacientes Alzheimer's disease as viewed by relatives of patients at public and private clinics

    Directory of Open Access Journals (Sweden)

    Luciana Pricoli Vilela

    2006-06-01

    Full Text Available OBJETIVO: Existem inúmeras questões éticas relacionadas ao atendimento médico de pacientes com doença de Alzheimer (DA, como a revelação do diagnóstico ao paciente, a realização de necrópsia para confirmação diagnóstica, além de aspectos relacionados aos cuidadores desses pacientes, submetidos a estresse físico e mental constantes. O presente trabalho buscou investigar estes temas comparando cuidadores familiares de pacientes com DA acompanhados em serviço público e privado. MÉTODOS: Vinte cuidadores familiares de pacientes com DA acompanhados em hospital universitário público e 20 cuidadores familiares de pacientes acompanhados em clínica privada foram entrevistados por meio de questionário específico que consistia em 36 questões sobre diagnóstico, tratamento e prognóstico da doença. RESULTADOS: Os dois grupos apresentaram distribuição similar por gênero e idade; o nível socioeconômico dos indivíduos acompanhados em clínica privada foi superior. Não foi observada diferença significativa de opiniões entre os grupos sobre a revelação ou não do diagnóstico de DA aos pacientes, com 42,5% do total de entrevistados se dizendo favoráveis à informação apenas da família. O número de cuidadores favoráveis à realização de necrópsia foi significativamente maior entre o grupo acompanhado em serviço público (35% contra 30% no serviço privado. Vinte cuidadores entrevistados (50% do total manifestaram, de forma espontânea, o desejo de que fosse realizado exame necroscópico com finalidade de pesquisa científica. CONCLUSÃO: A revelação diagnóstica da DA aos pacientes foi apoiada por mais da metade dos entrevistados, sem relação com nível socioeconômico. Esta variável, no entanto, influenciou a taxa de concordância quanto à realização de exame neuropatológico post-mortem.BACKGROUND: There are several ethical aspects related to the medical assistance of patients with Alzheimer's disease (AD

  10. Clinical Study on the Diagnosis and Treatment of Alzheimer's Disease%阿尔茨海默病临床诊治研究

    Institute of Scientific and Technical Information of China (English)

    齐智慧

    2014-01-01

    目的:探讨阿尔茨海默病的临床诊治。方法选取该院2010年1月-2012年1月间收治的阿尔茨海默病患者31例为观察组,回顾性分析其临床资料;选取同期在该院进行健康体检的老年人31例为对照组,用MRI检测两组研究对象的侧脑室体积,对比2010-2011年侧脑室变化情况。结果65岁以上的患者较65岁以下的患者比例显著升高(P<0.01),性别之间无统计学差异;临床主要表现为记忆力下降;简易智能量表评分均低于23分,其中重度痴呆占多数;超1/4的患者具有家族阳性史;2年内观察组患者左侧、右侧和双侧侧脑室体积明显大于正常组(P<0.01);观察组患者侧脑室体积随时间的推移呈明显递增趋势。结论该病的早期诊治仍为临床工作的重点,基因诊断和治疗可能具有较好的效果,各侧侧脑室体积动态变化情况可能是阿尔茨海默病患者的特征性影像学表现之一,可用于临床判断疾病的严重程度。%Objective To explore the clinical diagnosis and treatment of Alzheimer's disease. Methods 31 cases of patients with Alzheimer's disease admitted in our hospital from January, 2010 to January, 2012 were selected as the observation group, and the clinical data of them were analyzed retrospectively. And 31 cases of elderly people underwent healthy examination in our hospital during the same period were selected as the control group. MRI was used to detect lateral ventricular volume of the two groups of patients, and the lateral ventricle changes between 2010 and 2011 were compared. Results The proportion of patients over 65 years with the disease was significantly higher than that of the patients below the age of 65 (P<0.01), but there was no statistically significant difference between that of male patients and female patients; the main clinical manifestations were memory deteriora-tion; MMSE scores were lower than 23 points, severe dementia were

  11. Regional cerebral blood flow and its correlation with clinical assessment in senile dementia of Alzheimer type and multi-infarct dementia

    International Nuclear Information System (INIS)

    Twenty-one patients with senile dementia of Alzheimer type (SDAT), 11 patients with multi-infarct dementia (MID), and 6 healthy volunteers were examined by SPECT using Xe-inhalation method. These patients also underwent an intelligence test according to the Gottfries-Brane-Steen (GBS) scale. Patients with mild SDAT did not have a significantly decreased regional cerebral blood flow (rCBF). In moderate or severe cases, however, a significantly decreased rCBF was bilaterally observed in all regions, except for the basal ganglia. This was marked in the temporoparietal region. A group of moderate or severe MID patients had a significantly decreased rCBF especially in the basal ganglia. It was also observed in the temporoparietal region, but not in the frontal region. Among the SDAT patients, there was a good correlation between rCBF and GBS scale in all the regions, except for the basal ganglia. In the case of MID patients, correlations were observed both between rCBF in the left side of the brain and clinical findings according to the method of Hasegawa and between rCBF in the right side of the frontal region and the motor function on the GBS scale. These findings may have implications for the different pathophysiology between SDAT and MID. (N.K.)

  12. Alzheimer's Disease: Unraveling the Mystery

    Science.gov (United States)

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

  13. Frontotemporal dementia to Alzheimer's disease

    OpenAIRE

    Silveri, Maria Caterina

    2007-01-01

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

  14. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia: a proton magnetic resonance spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D. [Department of Imaging, Charing Cross Hospital and Dementia Research Group, University College London, Fulham Palace Road, W6 8RF, London (United Kingdom); Rai, G.S. [Department of Care of Older People, Whittington Hospital, Highgate Hill, London (United Kingdom)

    2003-08-01

    Previous magnetic resonance spectroscopy (MRS) studies have shown increased myo-inositol (MI) and decreased N-acetyl aspartate (NAA) levels in the parieto-occipital lobes of patients with Alzheimer's disease (AD) compared to those with other dementias and normal subjects. This study aimed to establish the quantitative relationship between metabolite ratios and degree of cognitive impairment in patients with mild to moderate AD and sub-cortical ischaemic vascular dementia (SIVD). Forty-four older people with clinical dementia were recruited from a memory clinic and followed up for 2.0-3.5 years; 20 cases were finally classified as probable AD, 18 as SIVD and 6 as mixed type. Mini Mental State Examination (MMSE) and short echo time single voxel automated MRS from the mesial parieto-occipital lobes were performed at the time of initial referral. Spearman rank correlation coefficients were calculated for MMSE scores and measured metabolite ratios MI/Cr, NAA/Cr, Cho/Cr and NAA/MI. The AD group showed a significant correlation between MMSE and NAA/MI (r=0.54, P=0.014) and NAA/Cr (r=0.48, P=0.033), and a negative, non-significant association with MI/Cr (r=-0.41, P=0.072). MI/Cr was negatively correlated with NAA/Cr (r=-0.51, P=0.021). Neither Cho/Cr ratios nor age correlated with cognitive function. The SIVD group showed no correlation between any of the measured metabolite ratios and MMSE score. This study reinforces the specific association between reduced NAA and increased MI levels in the parieto-occipital region and cognitive impairment in AD. MRS may have a role in evaluating disease progression and therapeutic monitoring in AD, as new treatments become available. (orig.)

  15. The relationship between cognitive impairment and in vivo metabolite ratios in patients with clinical Alzheimer's disease and vascular dementia: a proton magnetic resonance spectroscopy study

    International Nuclear Information System (INIS)

    Previous magnetic resonance spectroscopy (MRS) studies have shown increased myo-inositol (MI) and decreased N-acetyl aspartate (NAA) levels in the parieto-occipital lobes of patients with Alzheimer's disease (AD) compared to those with other dementias and normal subjects. This study aimed to establish the quantitative relationship between metabolite ratios and degree of cognitive impairment in patients with mild to moderate AD and sub-cortical ischaemic vascular dementia (SIVD). Forty-four older people with clinical dementia were recruited from a memory clinic and followed up for 2.0-3.5 years; 20 cases were finally classified as probable AD, 18 as SIVD and 6 as mixed type. Mini Mental State Examination (MMSE) and short echo time single voxel automated MRS from the mesial parieto-occipital lobes were performed at the time of initial referral. Spearman rank correlation coefficients were calculated for MMSE scores and measured metabolite ratios MI/Cr, NAA/Cr, Cho/Cr and NAA/MI. The AD group showed a significant correlation between MMSE and NAA/MI (r=0.54, P=0.014) and NAA/Cr (r=0.48, P=0.033), and a negative, non-significant association with MI/Cr (r=-0.41, P=0.072). MI/Cr was negatively correlated with NAA/Cr (r=-0.51, P=0.021). Neither Cho/Cr ratios nor age correlated with cognitive function. The SIVD group showed no correlation between any of the measured metabolite ratios and MMSE score. This study reinforces the specific association between reduced NAA and increased MI levels in the parieto-occipital region and cognitive impairment in AD. MRS may have a role in evaluating disease progression and therapeutic monitoring in AD, as new treatments become available. (orig.)

  16. What Do We Know About Preventing Alzheimer's? | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... One current trial, Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease Trial, or A4, is among a new generation of clinical trials testing therapies that might prevent, or at least delay, Alzheimer's ...

  17. Characteristics of patients with Alzheimer’s disease who switch to rivastigmine transdermal patches in routine clinical practice

    OpenAIRE

    López-Pousa S; Arranz FJ

    2013-01-01

    Secundino López-Pousa,1 Francisco Javier Arranz21Unit for Assessment of Memory and Dementia, Institut d’Assistència Sanitària de Girona, Salt, Girona, 2CNS Area, Medical Department and Health Innovation, Esteve, Barcelona, SpainBackground: The aim of this study was to assess the sociodemographic and clinical characteristics of patients with Alzheimer’s disease who switched from any oral cholinesterase inhibitor to rivastigmine patches.Metho...

  18. Differential X-ray phase contrast tomography of Alzheimer plaques in mouse models: perspectives for drug development and clinical imaging techniques

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is a looming threat on an ever-ageing population, with devastating effects on the human intellect. A particular characteristic lesion — the extracellular amyloid plaque — accumulates in the brain of AD patients during the course of the disease, and could therefore be used to monitor the progression of the disease, years before the first neurological symptoms appear. In addition, strategies for drug intervention in AD are often based on amyloid reduction, since amyloid plaques are hypothesized to be involved in a chain of reactions leading to the death of neurons. Developments in both fields would benefit from a microscopic technique that is capable of single plaque imaging, ideally in 3D. While such a non-destructive, single-plaque imaging technique does not yet exist for humans, it has been recently shown that synchrotron based differential X-ray phase contrast imaging can be used to visualize individual plaques at μm resolution in mouse models of AD ex-vivo. This method, which relies on a grating interferometer to measure refraction angles induced by fluctuations in the refractive index, yields a precise three-dimensional distribution of single plaques. These data could not only improve the understanding of the evolution of AD or the effectiveness of drugs, but could also help to improve reliable markers for current and future non-invasive clinical imaging techniques. In particular, validation of PET markers with small animal models could be rapidly carried out by co-registration of PET and DPC signals.

  19. The Alzheimer Pandemic: Is Paracetamol to Blame?

    OpenAIRE

    Jones, Günther Robert Norman

    2013-01-01

    Historical Background: The clinical recognition of a form of dementia closely resembling Alzheimer's disease dates from around 1800. The role of analgesics derived from coal-tar in the spread of the pandemic is traced in terms of the introduction of phenacetin (PN) in 1887; its nephrotoxicity; the observation of lesions characteristic of the disease by Fischer and Alzheimer; the discovery of paracetamol (PA) as the major metabolite of PN; the linking of kidney injury and dementia with high PN...

  20. Diagnosis and treatment of Alzheimer's disease

    International Nuclear Information System (INIS)

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

  1. Food, Eating and Alzheimer's

    Science.gov (United States)

    ... sell or share your name. Food, Eating and Alzheimer's Tweet Bookmark this page | Email | Print Regular, nutritious ... Encourage independence Map out a plan to approach Alzheimer's There are many questions you'll need to ...

  2. The Alzheimer's Project

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues The Alzheimer's Project Past Issues / Spring 2009 Table of Contents For ... this page please turn Javascript on. The Alzheimer's Project A 4-Part Documentary Series Starting May 10 ...

  3. The Alzheimer's Project

    Science.gov (United States)

    ... 10 at 9 p.m. Also at www.hbo.com/events/alzheimers Find out about the momentum ... Alzheimer's research and the latest resources for families HBO Documentary Films and the National Institute on Aging ...

  4. Treatments for Alzheimer's Disease

    Science.gov (United States)

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

  5. Seven Stages of Alzheimer's

    Science.gov (United States)

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

  6. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    Science.gov (United States)

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. PMID:26349946

  7. Synaptic changes in Alzheimer's disease in vivo

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Chu, L W

    2012-06-01

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

  9. Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-Alzheimer's risk metabolic phenotype.

    Science.gov (United States)

    Rettberg, Jamaica R; Dang, Ha; Hodis, Howard N; Henderson, Victor W; St John, Jan A; Mack, Wendy J; Brinton, Roberta Diaz

    2016-04-01

    Detecting at-risk individuals within a healthy population is critical for preventing or delaying Alzheimer's disease. Systems biology integration of brain and body metabolism enables peripheral metabolic biomarkers to serve as reporters of brain bioenergetic status. Using clinical metabolic data derived from healthy postmenopausal women in the Early versus Late Intervention Trial with Estradiol (ELITE), we conducted principal components and k-means clustering analyses of 9 biomarkers to define metabolic phenotypes. Metabolic clusters were correlated with cognitive performance and analyzed for change over 5 years. Metabolic biomarkers at baseline generated 3 clusters, representing women with healthy, high blood pressure, and poor metabolic phenotypes. Compared with healthy women, poor metabolic women had significantly lower executive, global and memory cognitive performance. Hormone therapy provided metabolic benefit to women in high blood pressure and poor metabolic phenotypes. This panel of well-established clinical peripheral biomarkers represents an initial step toward developing an affordable, rapidly deployable, and clinically relevant strategy to detect an at-risk phenotype of late-onset Alzheimer's disease. PMID:26973115

  10. Clinical Characteristics Analysis of Delirium Caused by Alzheimer's Patients Complicated with Cerebral Infarction 32 Cases%老年痴呆患者并发脑梗死所致谵妄32例临床特征分析

    Institute of Scientific and Technical Information of China (English)

    焦文菊

    2015-01-01

    Objective To explore alzheimer's patients complicated with cerebral infarction caused by clinical characteristics analysis of delirium. Methods Select our hospital from April 2012 to August 2013 hospitalized in our hospital and treatment of alzheimer's patients complicated with cerebral infarction caused by delirium of 32 cases of patients, the 32 cases of senile dementia patients compared with delirium after before delirium. Use of delirium scale (DSS), the Chinese version of simple intelligent mental state check table (MMSE) of 32 cases of alzheimer's patients complicated with cerebral infarction caused by delirium and delirium after evaluation. Result The DSS assessment delirium disappears, sleep-wake cycle disorders, behavioral changes occur two at the speed of recovery is best, disorientation, worst illusion two back to the environment. MMSE score delirium disappears to restore best language ability, memory ability to restore the worst. Conclusion Delirium caused by complicated with cerebral infarction in patients with alzheimer's disease clinical characteristics analysis is helpful to identify simple clinical alzheimer's disease and alzheimer's patients complicated with cerebral infarction caused by delirium, has great signiifcance on clinical research.%目的:探究老年痴呆患者并发脑梗死所致谵妄的临床特征分析。方法选取我院2012年4月至2013年8月在我院住院并接受治疗的老年痴呆患者并发脑梗死所致谵妄的患者32例,将32例老年痴呆患者谵妄前与谵妄后进行比较。利用谵妄量表(DSS)、中文版简易智能精神状态检查表(MMSE)对32例老年痴呆患者并发脑梗死所致谵妄及谵妄消失后进行测评。结果 DSS测评谵妄消失时,睡眠-觉醒周期紊乱、行为变化出现的速度两项恢复最好,定向力障碍、对环境的错觉两项恢复最差。MMSE评分谵妄消失时以语言能力恢复最好,回忆能力恢复最差。结论对老年痴呆患

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Jun Tang

    2012-01-01

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

  13. 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.

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-09-05

    Alzheimer`s disease is often diagnosed too late. Its etiology is still largely unknown and remains one of the big challenges in neurobiological fundamental research. Optimized early and differential diagnosis can be ensured by a dynamic concept of multidisciplinary diagnosis in cooperation between practitioners specializing in brain disorders, clinical psychogeriatric deprtments, and general practitioners. This, in turn, will enable individualized planning of further living conditions and care of Alzheimer patients and their relations as well as efficient and early pharmacotherapy and psychological intervention. (orig) [Deutsch] Die Alzheimer-Demenz kann heute mit grosser Sicherheit auch in der hausaerztlichen Praxis festgestellt werden. Dennoch werden Hirnleistungsstoerungen meist erst spaet im Krankheitsverlauf diagnostiziert. Oft bestehen dann bereits fortgeschrittene kognitive Beeintraechtigungen, die zu schweren psychosozialen und oekonomischen Belastungen innerhalb von Familie und Gesellschaft fuehren. Es sind mehr als 50 Erkrankungen beschrieben, die eine Demenz verursachen koennen. Die Alzheimer-Demenz macht davon den groessten Anteil aus und wirft durch ihre zunehmende Haeufigkeit erhebliche medizinische, pflegerische und soziooekonomische Probleme auf. Die weiterhin ungeklaerte Aetiologie ist eine der grossen Herausforderungen der neurobiologischen Grundlagenforschung. Aktuelle klinische Therapiestudien mit Acetylcholinesterase-Hemmern konnten ihre Wirksamkeit auf die kognitive Kernsymptomatik bei leichten und mittelgradig dementiellen Syndromen nachweisen. Durch ein dynamisches Konzept der multidisziplinaeren Diagnostik im Zusammenschluss zwischen spezialisierten Gedaechtnisambulanzen, klinisch-psychogeriatrischen Abteilungen und niedergelassenen Allgemein- und Fachaerzten kann eine optimierte Frueh- und Differentialdiagnostik bei Demenz-Patienten erfolgen. Dies erlaubt eine rechtzeitige individuelle Lebens- und Pflegeplanung fuer Alzheimer-Patienten und

  16. Alzheimer's Disease Facts and Figures

    Science.gov (United States)

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

  17. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

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

  18. A multi-center randomized proof-of-concept clinical trial applying [¹⁸F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's disease.

    Science.gov (United States)

    Tzimopoulou, Sofia; Cunningham, Vincent J; Nichols, Thomas E; Searle, Graham; Bird, Nick P; Mistry, Prafull; Dixon, Ian J; Hallett, William A; Whitcher, Brandon; Brown, Andrew P; Zvartau-Hind, Marina; Lotay, Narinder; Lai, Robert Y K; Castiglia, Mary; Jeter, Barbara; Matthews, Julian C; Chen, Kewei; Bandy, Dan; Reiman, Eric M; Gold, Michael; Rabiner, Eugenii A; Matthews, Paul M

    2010-01-01

    Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPARγ agonist Rosiglitazone XR versus placebo in 80 mild to moderate AD patients. Secondary objectives included testing for reduction in the progression of brain atrophy and improvement in cognition. Active treatment was associated with a sustained but not statistically significant trend from the first month for higher mean values in Kiindex and CMRgluindex, novel quantitative indices related to the combined forward rate constant for [18F]FDG uptake and to the rate of cerebral glucose utilization, respectively. However, neither these nor another analytical approach recently validated using data from the Alzheimer's Disease Neuroimaging Initiative indicated that active treatment decreased the progression of decline in brain glucose metabolism. Rates of brain atrophy were similar between active and placebo groups and measures of cognition also did not suggest clear group differences. Our study demonstrates the feasibility of using [18F]FDG-PET as part of a multi-center therapeutics trial. It suggests that Rosiglitazone is associated with an early increase in whole brain glucose metabolism, but not with any biological or clinical evidence for slowing progression over a 1 year follow up in the symptomatic stages of AD. PMID:20930300

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

    Science.gov (United States)

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

    2011-11-01

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

  20. Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center

    OpenAIRE

    Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E; Frosch, Matthew P.; Betensky, Rebecca A.; Hyman, Bradley T.

    2013-01-01

    To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating–Sum of Boxes in the...

  1. Clinical and Molecular Studies Reveal a PSEN1 Mutation (L153V) in a Peruvian Family with Early-Onset Alzheimer's Disease

    OpenAIRE

    Cornejo-Olivas, Mario R.; Yu, Chang-En; Mazzetti, Pilar; Mata, Ignacio F.; Meza, Maria; Lindo-Samanamud, Saul; Leverenz, James B.; Bird, Thomas D.

    2014-01-01

    Presenilin 1 (PSEN1) gene mutations are found in 30 to 70% of familial early onset Alzheimer disease (EOAD) cases (onset G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease.

  2. Clinical differences in patients with alzheimer's disease according to the presence or absence of anosognosia: implications for perceived quality of life

    OpenAIRE

    Conde Sala, Josep Lluís; Reñé-Ramírez, Ramón; Turró Garriga, Oriol; Gascón-Bayarri, J.; Juncadella i Puig, Montserrat; Moreno-Cordón, L.; Viñas Diez, V.; Garre Olmo, Josep

    2013-01-01

    Abstract This study aimed to determine the factors that predict anosognosia in patients with Alzheimer's disease (AD) and to examine the effect of anosognosia on patient and caregiver perceptions of the patient's quality of life (QoL-p), using a cross-sectional design with 164 patients and their caregivers. Instruments of measurement included Anosognosia Questionnaire-Dementia, Geriatric Depression Scale, Quality of Life in AD (QoL-AD), Disability Assessment for Dementia, Neuropsychiatric Inv...

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

    Science.gov (United States)

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

    2016-07-01

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

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

    OpenAIRE

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

    2000-01-01

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

  5. 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...

  6. 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...

  7. 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...

  8. Neuroimaging of Alzheimer's disease

    International Nuclear Information System (INIS)

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

  9. Alzheimer, mitochondria and gender.

    Science.gov (United States)

    Grimm, Amandine; Mensah-Nyagan, Ayikoe Guy; Eckert, Anne

    2016-08-01

    Epidemiological studies revealed that two-thirds of Alzheimer's disease (AD) patients are women and the drop of sex steroid hormones after the menopause has been proposed to be one risk factor in AD. Similarly, the decrease of circulating testosterone levels with aging may also increase the risk of AD in men. Studies attest the neuroprotective effects of sex hormones in animal models of AD, but clinical trial data remain controversial. Here, we discuss the implication of mitochondria in gender differences observed in AD patients and animal models of AD. We summarize the role of mitochondria in aging and AD, pointing to the potential correlation between the loss of sex hormones and changes in the brain redox status. We discuss the protective effects of the sex hormones, estradiol, progesterone and testosterone with a specific focus on mitochondrial dysfunction in AD. The understanding of pathological processes linking the loss of sex hormones with mitochondrial dysfunction and mechanisms that initiate the disease onset may open new avenues for the development of gender-specific therapeutic approaches. PMID:27139022

  10. 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....

  11. SPECT in Alzheimer`s disease and the dementias

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-31

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

  12. 2014-2015 Alzheimer's Disease Progress Report

    Science.gov (United States)

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

  13. Neuroinflammation in Alzheimer's disease

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Communication and Alzheimer's

    Science.gov (United States)

    ... We will not sell or share your name. Communication and Alzheimer's Tweet Bookmark this page | Email | Print ... Best ways for you to communicate Changes in communication In addition to changes in the brain caused ...

  15. About Alzheimer's Disease: Causes

    Science.gov (United States)

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

  16. Alzheimer's disease and stigmatization

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    1991-01-01

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

  18. Pyrosequencing revealed shifts of prokaryotic communities between healthy and disease-like tissues of the Red Sea sponge Crella cyathophora

    KAUST Repository

    Gao, Zhao-Ming

    2015-06-11

    Sponge diseases have been widely reported, yet the causal factors and major pathogenic microbes remain elusive. In this study, two individuals of the sponge Crella cyathophora in total that showed similar disease-like characteristics were collected from two different locations along the Red Sea coast separated by more than 30 kilometers. The disease-like parts of the two individuals were both covered by green surfaces, and the body size was much smaller compared with adjacent healthy regions. Here, using high-throughput pyrosequencing technology, we investigated the prokaryotic communities in healthy and disease-like sponge tissues as well as adjacent seawater. Microbes in healthy tissues belonged mainly to the Proteobacteria, Cyanobacteria and Bacteroidetes, and were much more diverse at the phylum level than reported previously. Interestingly, the disease-like tissues from the two sponge individuals underwent shifts of prokaryotic communities and were both enriched with a novel clade affiliated with the phylum Verrucomicrobia, implying its intimate connection with the disease-like Red Sea sponge C. cyathophora. Enrichment of the phylum Verrucomicrobia was also considered to be correlated with the presence of algae assemblages forming the green surface of the disease-like sponge tissues. This finding represents an interesting case of sponge disease and is valuable for further study.

  19. Facilitating Alzheimer disease research recruitment.

    Science.gov (United States)

    Grill, Joshua D; Galvin, James E

    2014-01-01

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

  20. Donepezil Combined with Natural Hirudin Improves the Clinical Symptoms of Patients with Mild-to-Moderate Alzheimer's Disease: A 20-Week Open-Label Pilot Study

    Directory of Open Access Journals (Sweden)

    De-qiang Li, Yu-ping Zhou, Han Yang

    2012-01-01

    Full Text Available Aim: To evaluate the efficacy and safety of donepezil plus natural hirudin in patients with mild-to-moderate Alzheimer's Disease. Methods: In the 20-week, randomized, open-label and controlled study, 84 patients received either donepezil (5 mg/day for the first 4 weeks and 10 mg/day thereafter or donepezil plus natural hirudin (3 g/day treatment. Efficacy was reflected by the change of the total scores of Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog, Activities of Daily Life (ADL and Neuropsychiatric Inventory (NPI. Results: The patients with the donepezil plus natural hirudin treatment showed more significant improvement in the daily activities and the decline of the cognition than those with donepezil treatment. Significant difference was present in the groups since the 8th week. No group difference was found in the NPI change. However, within the hirudin treatment group, more powerful efficacy including NPI assessment was found in the patients with vascular risk factors (VRF as comparing to with those without VRF. The combination of donepezil and natural hirudin was well tolerated. The dropout rate was greater in the donepezil and natural hirudin (50% treatment group than in the donepezil (39% treatment group. Similar result was found in the incidence of adverse events (23.8% vs 19.0%, but there was no statistical difference between the two groups. Adverse events were the most common reason for the dropout. Although hemorrhage and hypersensitiveness were more common in donepezil plus Maixuekang treatment (11.9% and 7.1% group than in donepezil treatment (2.4% and 2.4% group, no significant difference was present between the two groups. Economic problem was another important reason for the patients' withdrawal. Conclusions: Compared with the donepezil treatment in the patients with mild-to-moderate AD, our results suggest that donepezil combined with natural hirudin may improve the treatment effects in the ADL, BPSD and

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

    OpenAIRE

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

    2009-01-01

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

  2. Alien hand sign in association with Alzheimer's histopathology.

    OpenAIRE

    Ball, J. A.; Lantos, P. L.; Jackson, M.; Marsden, C D; Scadding, J W; Rossor, M. N.

    1993-01-01

    A 68 year old man is described with an alien left hand, cortical myoclonus, bilateral parietal lobe dysfunction and memory impairment but preserved language skills. The clinical diagnosis was of corticobasal degeneration but at necropsy, four years after the onset of symptoms, the pathology was of Alzheimer's disease together with some scattered chromatolytic pale neurons in the cerebral cortex. The alien hand sign has not previously been described in Alzheimer's dementia and is an illustrati...

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

    OpenAIRE

    Mega, M; L. Lee; Dinov, I.; Mishkin, F; Toga, A.; Cummings, J.

    2000-01-01

    BACKGROUND—Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities.
OBJECTIVES—To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT).
METHODS—Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equ...

  4. Dementia of the Alzheimer type: current state of the problem

    OpenAIRE

    N A Tyuvina; V. V. Balabanova

    2014-01-01

    The current knowledge on epidemiology, diagnosis, and treatment of Alzheimer's disease and dementia of the Alzheimer type are presented. Various approaches to therapy based on current understanding of the pathogenesis of the degenerative process are discussed with allowance for the clinical features of the disease (psychopathologic symptoms and stage of the disease). Special attention is paid to compensatory therapy aimed at compensating for the deficit in cholinergic and glutamatergic neurot...

  5. African-Americans and Alzheimer's

    Science.gov (United States)

    ... Share Plus on Google Plus African-Americans and Alzheimer's alz.org | IHaveAlz Introduction 10 Warning Signs Brain ... African-Americans are at a higher risk for Alzheimer's disease. Many Americans dismiss the warning signs of ...

  6. Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

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

  7. Neuropathology of Alzheimer's Disease

    Science.gov (United States)

    Perl, Daniel P.

    2010-01-01

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

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

    OpenAIRE

    Wolozin, Benjamin

    2012-01-01

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

  9. APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies Asociación positiva entre APOE épsilon4 y demencia de Alzheimer en una serie clinica en Bogotá (Colombia y revision de los estudios latinoamericanos

    Directory of Open Access Journals (Sweden)

    Martine Jacquier

    2001-03-01

    Full Text Available OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs including familial ( n =30 and sporadic AD cases (n= 53 diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44 had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6 between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%. A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75. CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.OBJETIVO: Como la fortaleza de la asociación entre el alelo épsilon4 del gen APOE y la enfermedad de Alzheimer (EA difiere entre grupos étnicos, quisimos evaluar si esta asociación existe en pacientes colombianos. MÉTODOS: Realizamos una genotipificación para el gen de la apolipoproteina E (APOE en una muestra clínica de 83 pacientes con EA no relacionados, de inicio predominantemente tardío (> 65 años, incluyendo casos familiares (n=30 y esporádicos (n=53 diagnosticados según los criterios del NINCDS-ADRDA y evaluados por un equipo multi-disciplinario. Los sujetos control (n= 44 no presentaban deterioro cognoscitivo de acuerdo con la entrevista médica y la evaluación neuropsicológica. RESULTADOS: Hallamos una alta asociación (OR= 5.1; IC95% 1.9- 13.6 entre APOE épsilon4 y EA en la serie de casos de inicio tardío y con agregación familiar en 24 sujetos (28.9%. Una asociación negativa, estadísticamente significativa, fue encontrada

  10. Prediabetes and Alzheimer's Disease

    Science.gov (United States)

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

    2015-01-01

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

  11. Prediabetes and alzheimer's disease

    Directory of Open Access Journals (Sweden)

    V R Bitra

    2015-01-01

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

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

    OpenAIRE

    Rothman, Sarah M.; Mattson, Mark P.

    2009-01-01

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

  13. Diagnosis and management of Alzheimer's disease

    OpenAIRE

    Burns, Alistair

    2000-01-01

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

  14. Memantine Attenuates Alzheimer’s Disease-Like Pathology and Cognitive Impairment

    Science.gov (United States)

    Wang, Xiaochuan; Blanchard, Julie; Iqbal, Khalid

    2015-01-01

    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. PMID:26697860

  15. Alzheimer's Dye Test?

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Massachusetts Institute of Technology (MIT) scientists have developed a new dye that could offer noninvasive early diagnosis of Alzheimer's disease, a discovery that could aid in monitoring the progression of the disease and in studying the efficacy of new treatments to stop it. The work is published in Angewandte Chemie. Today, doctors can only…

  16. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    Science.gov (United States)

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  17. High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.

    Directory of Open Access Journals (Sweden)

    Lisa Gruber

    Full Text Available BACKGROUND: Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis. METHODS: TNF(ΔARE/WT mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors. RESULTS: HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria. CONCLUSIONS: HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease

  18. The olfactory deficit and fMRI in the Alzheimer's disease

    International Nuclear Information System (INIS)

    Olfactory deficit is a common symptom occurring at the early stage of Alzheimer's disease, the purpose of this review is to summarize MRI research on olfactory deficit in the Alzheimer's disease and potential clinical relevance of fMRI in this area. (authors)

  19. Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

    OpenAIRE

    Smith, Gwenn S.; Kramer, Elisse; Ma, Yilong; Hermann, Carol R.; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David

    2009-01-01

    Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable contro...

  20. An Experimental Approach to Detecting Dementia in Down Syndrome: A Paradigm for Alzheimer's Disease

    Science.gov (United States)

    Nelson, Linda D.; Scheibel, Kevin E.; Ringman, John M.; Sayre, James W.

    2007-01-01

    Measures developed from animal models of aging may detect dementia of the Alzheimer's type in a population at-risk for Alzheimer's disease (AD). Although, by middle age, individuals with Down syndrome (DS) show an extraordinarily high prevalence of AD-type pathology, their severe idiopathic cognitive deficits tend to confound the "clinical"…

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

    Science.gov (United States)

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

  2. Alzheimer's Disease in People with Down Syndrome

    Science.gov (United States)

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

  3. Caregiving for Alzheimer's Disease or Other Dementia

    Science.gov (United States)

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

  4. Home Safety for People with Alzheimer's Disease

    Science.gov (United States)

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

  5. Adapting Activities for People with Alzheimer's Disease

    Science.gov (United States)

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

  6. Keeping the Person with Alzheimer's Disease Safe

    Science.gov (United States)

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

  7. 10 Early Signs and Symptoms of Alzheimer's

    Science.gov (United States)

    ... 10 Warning Signs Checklist 10 warning signs of Alzheimer's: Memory loss that disrupts daily life One of ... related memory loss and other changes compared to Alzheimer's Signs of Alzheimer's Typical age-related changes Poor ...

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

    Science.gov (United States)

    Bredesen, Dale E

    2015-08-01

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

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

    Science.gov (United States)

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

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'. PMID:26025658

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

    Institute of Scientific and Technical Information of China (English)

    Selina M(a)rdh

    2013-01-01

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

  11. The immunotherapy of Alzheimer's disease

    OpenAIRE

    Weksler Marc E

    2004-01-01

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

  12. Revisiting rodent models: Octodon degus as Alzheimer's disease model?

    Science.gov (United States)

    Steffen, Johannes; Krohn, Markus; Paarmann, Kristin; Schwitlick, Christina; Brüning, Thomas; Marreiros, Rita; Müller-Schiffmann, Andreas; Korth, Carsten; Braun, Katharina; Pahnke, Jens

    2016-01-01

    Alzheimer's disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these 'engineered' models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural 'sporadic Alzheimer's disease model' with 'Alzheimer's disease-like neuropathology'. To unveil advantages over the 'artificial' mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer's disease patients or transgenic disease models. PMID:27566602

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-06-19

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

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

    Science.gov (United States)

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

    2015-12-01

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

  15. Medical foods for Alzheimer's disease.

    Science.gov (United States)

    Shah, Raj C

    2011-06-01

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

  16. Genetic heterogeneity and Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  17. Biomarkers for Alzheimer's disease therapeutic trials.

    Science.gov (United States)

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

    2011-12-01

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

  18. Cognitive debt and Alzheimer's disease.

    Science.gov (United States)

    Marchant, Natalie L; Howard, Robert J

    2015-01-01

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

  19. Scintigraphic appearance of Alzheimer diesase

    International Nuclear Information System (INIS)

    Alzheimer disease (AD) is a devastating affliction of the elderly that has reached epidemic proportions. It produces regional abnormalities of brain blood flow and metabolism that may have diagnostic utility. In this paper the author determine the predictive value of Tc-99m HMPAO SPECT for detecting AD based on the prospective study of 132 consecutive patients coming to their nuclear medicine clinical unit for evaluation of memory loss or cognitive abnormalities. The final diagnosis was determined during clinical follow-up of 10.1 months ± 10.8. A final diagnosis was established in 113 patients, 52 of whom had AD. The probability of AD was 0.19 for normal perfusion 0.82 for bilateral posterotemporal and/or parietal defects, 0.77 for bilateral posterotemporal and/or parietal defects with additional defects, 0.57 for unilateral posterotemporal and/or parietal defects with or without additional defects, 0.25 for defects not involving the posterotemporal and/or parietal cortex, and 0.0 for small cortical defects. Of nine patients with bilateral posterotemporal and/or parietal defects with AD, six had Parkinson disease dementia

  20. Identical twins with Alzheimer's disease.

    OpenAIRE

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

    1983-01-01

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

  1. Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice

    OpenAIRE

    Huang, Huang; Wang, Linmei; Cao, Min; Marshall, Charles; Gao, Junying; XIAO, NA; Hu, Gang; Xiao, Ming

    2015-01-01

    Background: Alzheimer’s disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer’s disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions be...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  3. Paradigm Shift in Treatment of Alzheimer's Disease: Zinc Therapy Now a Conscientious Choice for Care of Individual Patients

    OpenAIRE

    Hoogenraad, Tjaard U.

    2011-01-01

    Breakthrough in treatment of Alzheimer's disease with a shift from irrational dangerous chelation therapy to rational safe evidence based oral zinc therapy. Evidence based medicine: After synthesizing the best available clinical evidence I conclude that oral zinc therapy is a conscientious choice for treatment of free copper toxicosis in individual patients with Alzheimer's disease. Hypothesis 1: Age related free copper toxicosis is a causal factor in pathogenesis of Alzheimer's disease. Ther...

  4. 脑脊液tau蛋白预测阿尔茨海默病的Meta分析%Clinical value of tau protein in cerebrospinal fluid for prediction of Alzheimer's disease: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    耿劲松; 董建成; 倪衡建; 施李丽; 吴辉群; 蒋葵

    2011-01-01

    Objective To evaluate the efficiency and accuracy of total tau (t-tau) and phosphorylated tau (p-tau) proteins in cerebrospinal fluid (CSF) as biomarkers for predicting Alzheimer's disease (AD). Methods The published clinical literatures which aimed to investigate the concentration of tau protein to predict the conversion of mild cognitive impairment (MCI) to AD were retrieved. The quality of all the included literatures was assessed. Meta-analysis was carried out by the software Review Manager 5. 1 and Meta Disk 1.4. Results Fifteen literatures that met the inclusion criteria were included in this study. The baseline concentrations (pg,/mL) of both t-tau and p-tau in MCI to AD patients were higher than those in control group. The weighted mean difference (WMD) of t-tau in MCI to AD patients was 320.7, 95%CI: 274.2-367.3, and WMD of p-tau was 32.8, 95%CI: 29.5-36.0). Overall diagnostic odds ratios (DOR) of t-tau and p-tau were 14.1 (95% CI: 8.2-24.4) and 22.4 (95% CI: 10.4-48.3) respectively. Conclusion Tau in CSF may be an important diagnostic marker for predicting AD.%目的 评价脑脊液(CSF)总tau蛋白(t-tau)和磷酸化tau蛋白(P-tau)浓度预测阿尔茨海默病(Alzheimer'S disease,AD)的有效性和准确性.方法 全面检索tau蛋白浓度预测轻度认知功能障碍(mild cognitive impairment,MCI)转化为AD的诊断性试验文献,评价纳入文献的质量,用Review Manager 5.1和Meta Disk 1.4软件进行Meta分析,计算合并效应量.结果 共纳入15项研究,MCI进展为AD的t-tau基线浓度(pg/mL)高于对照组[加权均数差(WMD):320.7;95%CI:274.2~367.3],p-tau基线浓度(pg/mL)亦高于时照组(WMD:32.8;95%CI:29.5~36.0).t-tau预测AD的诊断优势比(diagnostic odds ration,DOR)为14.1(95%CI:8.2~24.4);p-tau的DOR为22.4(95%CI:10.4~48.3).结果 CSF中tau蛋白可作为预测AD发生的重要指标.

  5. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  8. Psychiatric Symptoms in Adults with Down Syndrome and Alzheimer's Disease

    Science.gov (United States)

    Urv, Tiina K.; Zigman, Warren B.; Silverman, Wayne

    2010-01-01

    Changes in psychiatric symptoms related to specific stages of dementia were investigated in 224 adults 45 years of age or older with Down syndrome. Findings indicate that psychiatric symptoms are a prevalent feature of dementia in the population with Down syndrome and that clinical presentation is qualitatively similar to that seen in Alzheimer's…

  9. Alzheimer's disease and euthanasia.

    Science.gov (United States)

    Alvargonzález, David

    2012-12-01

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

  10. 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...... diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta...

  11. Why Do We Get Alzheimer's Disease?

    International Nuclear Information System (INIS)

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

  12. 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 ...

  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. [Aβ immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

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

  15. Micronutrients and Alzheimer's disease.

    Science.gov (United States)

    Staehelin, Hannes B

    2005-11-01

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

  16. [Rehabilitation in Alzheimer's dementia].

    Science.gov (United States)

    Cicconetti, P; Fionda, A; Zannino, G; Ettorre, E; Marigliano, V

    2000-09-01

    Alzheimer's disease is a neurodegenerative disease that causes a progressive decline of cognitive and behavioural functions. The simultaneous presence of these disorders requires a treatment not only for cognitive decline, but also for behavioural symptoms, depression and caregiver's stress. Research has made many efforts to develop a wide range of treatments, different from current pharmacological therapy, which is not resolutive, owing to the absence of an exact etiopathogenetic mechanism. Since new drugs have not been shown to be really effective in slowing cognitive impairment, various forms of rehabilitative interventions have been proposed in order to treat Alzheimer's disease. Their efficacy in the improvement of cognitive functions is still not completely clear. Surely, interesting results have been obtained from studies about Reality Orientation Therapy, Occupational Therapy and Memory Training. Music therapy might provide a new form of rehabilitative intervention, especially acting on the reducing of behavioural symptoms. These alternative forms of non pharmacological treatment may have a positive effect on caregiver. The heavy emotional burden of seeing a loved one becoming confused and isolated and of having to accept new responsibilities, may be reduced by rehabilitative supports, complementary to the pharmacological therapy. Caregiver stress could be reduced in two ways: by promoting the hope that something is being done for the patient and providing free time for himself. PMID:11021168

  17. Exosomes in Alzheimer's disease.

    Science.gov (United States)

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

    2016-07-01

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

  18. The role of chemical engineering in medicinal research including Alzheimer's.

    Science.gov (United States)

    Kontogeorgis, Georgios M

    2015-01-01

    Various disciplines of chemical engineering, especially thermodynamics and kinetics, play an important role in medicinal research and this has been particularly recognized during the last 10-15 years (von Stockar and van der Wielen, J Biotechnol 59:25, 1997; Prausnitz, Fluid Phase Equilib 53:439, 1989; Prausnitz, Pure Appl Chem 79:1435, 2007; Dey and Prausnitz, Ind Eng Chem Res 50:3, 2011; Prausnitz, J Chem Thermodynamics 35:21, 2003; Tsivintzelis et al. AIChE J 55:756, 2009). It is expected that during the twenty-first century chemical engineering and especially thermodynamics can contribute as significantly to the life sciences development as it has been done with the oil and gas and chemical sectors in the twentieth century. Moreover, it has during the recent years recognized that thermodynamics can help in understanding diseases like human cataract, sickle-cell anemia, Creuzfeldt-Jacob ("mad cow" disease), and Alzheimer's which are connected to "protein aggregation." Several articles in the Perspectives section of prominent chemical engineering journals have addressed this issue (Hall, AIChE J 54:1956, 2008; Vekilov, AIChE J 54:2508, 2008). This work reviews recent applications of thermodynamics (and other areas of chemical engineering) first in drug development and then in the understanding of the mechanism of Alzheimer's and similar diseases. PMID:25416110

  19. Systematic review of atorvastatin for the treatment of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yuan Sun; Genfa Wang; Zhihong Pan; Shuyan Chen

    2012-01-01

    OBJECTIVE: To assess the clinical efficacy and safety of atorvastatin in the treatment of Alz-heimer's disease.DATA SOURCES: Medline (1948/2011-04), Embase (1966/2011-04), Cochrane Library (Issue 3, 2011), Chinese National Knowledge Infrastructure (1989/2011-04), and the Chinese Biomedical Literature Database (1979/2011-04) were searched for randomized clinical trials regardless of lan-guage. Abstracts of conference papers were manually searched. Furthermore, Current Controlled Trials (http://controlled-trials.com), Clinical Trials.gov (http://clinicaltrials.gov), and Chinese Clinical Trial Registry (http://www.chictr.org) were also searched.Key words included Alzheimer disease, dementia, cognition, affection, memory dysfunction, hydroxymethylglutaryl-CoA reductase inhibitors, atorvastatin and statins.DATA SELECTION: Randomized controlled trials of grade A or B according to quality evaluation criteria of the Cochrane Collaboration were selected, in which atorvastatin and placebo were used to evaluate the effects of atorvastatin in the treatment of Alzheimer's disease. Study methodological quality was evaluated based on criteria described in Cochrane Reviewer's Handbook 5.0.1. Revman 5.1 software was used for data analysis.MAIN OUTCOME MEASURES: Clinical efficacy, safety, withdrawal from the studies, and withdrawal due to adverse effects.CONCLUSION: There is insufficient evidence to recommend atorvastatin for the treatment of mild to moderate Alzheimer's disease, because there was no benefit on general function, cognitive function or mental/behavior abnormality outcome measures. Efficacy and safety need to be confirmed by larger and higher quality randomized controlled trials, especially for moderate to severe Alzheimer's disease, because results of this systematic review may be limited by selection bias, implementation bias, as well as measurement bias.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  1. Adult-onset opsoclonus-myoclonus-ataxia syndrome as a manifestation of brazilian lyme disease-like syndrome: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Angelina Maria Martins Lino

    2014-03-01

    Full Text Available Described in 1962, the opsoclonus-myoclonus-ataxia syndrome (OMAS is a rare, neurologically debilitating disorder with distinct characteristics that may begin in childhood or adult life. Although many cases remain without etiological diagnosis, others are related to neoplasms and infectious diseases. We report a 41-year-old previously healthy male with an 8-day history of headache, vertigo, nausea, vomiting, and nystagmus. After a normal brain computed tomography and lymphocytic pleocytosis in cerebral spinal fluid (CSF, intravenous acyclovir therapy was initiated in the emergency room. On the third day of hospitalization, the diagnosis of OMAS was made based on the presence of chaotic and irregular eye movements, dysarthric speech, gait instability, generalized tremor, and myoclonic jerks. In the face of his neurological worsening, ampicillin followed by nonspecific immunotherapy (methylprednisolone and intravenous immunoglobulin was prescribed, with mild clinical improvement. After a thorough laboratory workup, the definite diagnosis of neuroborreliosis was established and ceftriaxone (4 g/daily/3wks and doxycycline (200 mg/day/2 mo was administered. Toward the end of the ceftriaxone regimen, the neurologic signs substantially improved. We believe this to be the first case description of OMAS as clinical presentation of Brazilian Lyme disease-like syndrome (Baggio-Yoshinari syndrome.

  2. Analysis of Regional Cerebral Blood Flow Using 99mTc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

    International Nuclear Information System (INIS)

    99mTc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, 99mTc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

  3. Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success?

    Science.gov (United States)

    Winblad, B; Brodaty, H; Gauthier, S; Morris, J C; Orgogozo, J M; Rockwood, K; Schneider, L; Takeda, M; Tariot, P; Wilkinson, D

    2001-07-01

    The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease. PMID:11466744

  4. Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

  5. Demonstration of a reduction in muscarinic receptor binding in early Alzheimer`s disease using iodine-123 dexetimide single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Claus, J.J. [Department of Neurology, Academic Medical Center, Amsterdam (Netherlands); Dubois, E.A. [Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Booij, J. [Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Habraken, J. [Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Munck, J.C. van [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Herk, M. van [The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verbeeten, B. Jr. [Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Royen, E.A. van [Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    1997-06-10

    Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer`s disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [{sup 123}I]4-iododexetimide in five mildly affected patients with probable Alzheimer`s disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [{sup 123}I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intra-observer variability was 3.6% and inter-observer results showed consistent differences in [{sup 123}I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [{sup 123}I]4-iododexetimide binding is reduced in patients with mild probable Alzheimer`s disease in areas of temporal and temporo-parietal cortex. (orig.). With 1 fig., 4 tabs.

  6. [Music therapy and Alzheimer disease].

    Science.gov (United States)

    Tromeur, Emilie

    2014-01-01

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

  7. The Danish Alzheimer intervention study

    DEFF Research Database (Denmark)

    Waldemar, G; Waldorff, F B; Buss, D V;

    2011-01-01

    Background: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline characteri......Background: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline...

  8. Alzheimer's disease and stigmatization

    Directory of Open Access Journals (Sweden)

    Dimitrios Kosmidis

    2012-04-01

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

  9. Chronic Traumatic Encephalopathy Presenting as Alzheimer's Disease in a Retired Soccer Player.

    Science.gov (United States)

    Grinberg, Lea T; Anghinah, Renato; Nascimento, Camila Fernandes; Amaro, Edson; Leite, Renata P; Martin, Maria da Graça M; Naslavsky, Michel S; Takada, Leonel T; Filho, Wilson Jacob; Pasqualucci, Carlos A; Nitrini, Ricardo

    2016-07-29

    The relationship between soccer and chronic traumatic encephalopathy (CTE) is not well established. We report clinicopathological correlations in an 83-year-old retired center-back soccer player, with no history of concussion, manifesting typical Alzheimer-type dementia. Examination revealed mixed pathology including widespread CTE, moderate Alzheimer's disease, hippocampal sclerosis, and TDP-43 proteinopathy. This case adds to a few CTE cases described in soccer players. Furthermore, it corroborates that CTE may present clinically as typical Alzheimer-type dementia. Further studies investigating the extent to which soccer is a risk for CTE are needed. PMID:27472879

  10. Apatia na doença de Alzheimer Apathy in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Antônio Lúcio Teixeira-Jr

    2006-09-01

    Full Text Available Apatia é a mais comum síndrome neuropsiquiátrica na doença de Alzheimer, afetando entre 30 e 60% dos pacientes. Pode ser definida como perda de motivação e se manifesta com alterações afetivas, cognitivas e comportamentais, determinando, respectivamente, redução da resposta emocional, perda de autocrítica e retração social. Nesse artigo, são apresentadas as características clínicas da síndrome apática e suas perspectivas terapêuticas. Conclui-se que há uma superposição considerável entre apatia e depressão na doença de Alzheimer, mas ambas as condições são consideradas síndromes independentes. Intervenções farmacológicas para apatia incluem psicoestimulantes, como o metilfenidato, agentes dopaminérgicos e inibidores de colinesterase; mas os resultados são controversos e não há tratamento estabelecido.Apathy is the most common neuropsychiatry syndrome in Alzheimer's disease affecting 30-60% of patients. It can be defined as a loss of motivation and manifests in affect, cognition and behavioral changes, determining blunted emotional response, lack of insight and social retraction, respectively. In this paper, the clinical features and the therapeutic perspectives of apathy are presented. There is considerable overlap between apathy and depression in Alzheimer's disease, but both are considered discrete syndromes. Pharmacological interventions for apathy include psychostimulants, such as methylphenidate, dopaminergic agents and cholinesterase inhibitors, but the results are controversial and there is no established treatment.

  11. Cognitive Factors Affecting Free Recall, Cued Recall, and Recognition Tasks in Alzheimer's Disease

    OpenAIRE

    YAMAGISHI, Takashi; Sato, Takuya; Sato, Atsushi; Imamura, Toru

    2012-01-01

    Background/Aims Our aim was to identify cognitive factors affecting free recall, cued recall, and recognition tasks in patients with Alzheimer's disease (AD). Subjects: We recruited 349 consecutive AD patients who attended a memory clinic. Methods Each patient was assessed using the Alzheimer's Disease Assessment Scale (ADAS) and the extended 3-word recall test. In this task, each patient was asked to freely recall 3 previously presented words. If patients could not recall 1 or more of the ta...

  12. Early Alzheimer's Linked to Brain 'Leakage'

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159116.html Early Alzheimer's Linked to Brain 'Leakage' Normally, blood-brain barrier ... HealthDay News) -- People in the early stages of Alzheimer's disease may have more "leaks" in the barrier ...

  13. Deep Brain Stimulation Tested for Early Alzheimer's

    Science.gov (United States)

    ... 160137.html Deep Brain Stimulation Tested for Early Alzheimer's Although treatment seems safe, benefit isn't yet ... brain stimulation appears safe for people with early Alzheimer's disease -- and might even slow down memory loss ...

  14. Alzheimer's Gene May Show Effects in Childhood

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159854.html Alzheimer's Gene May Show Effects in Childhood Brain scans ... 13, 2016 (HealthDay News) -- A gene related to Alzheimer's disease may start to show effects on brain ...

  15. Imagine stopping the progression of Alzheimer's

    Science.gov (United States)

    ... Issue Past Issues Imagine stopping the progression of Alzheimer's Past Issues / Fall 2006 Table of Contents For ... I have friends and loved ones suffering from Alzheimer's. But I can imagine… and hope for… a ...

  16. Alzheimer's May Hamper Ability to Perceive Pain

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159988.html Alzheimer's May Hamper Ability to Perceive Pain People with ... 20, 2016 WEDNESDAY, July 20, 2016 (HealthDay News) -- Alzheimer's disease may affect people's ability to recognize when ...

  17. Early Alzheimer's Linked to Brain 'Leakage'

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159116.html Early Alzheimer's Linked to Brain 'Leakage' Normally, blood-brain barrier ... HealthDay News) -- People in the early stages of Alzheimer's disease may have more "leaks" in the barrier ...

  18. Underweight Seniors May Have Added Alzheimer's Risk

    Science.gov (United States)

    ... fullstory_160278.html Underweight Seniors May Have Added Alzheimer's Risk Study links lower body weight to increased ... older adults' risk of the memory-robbing disorder Alzheimer's disease, new research suggests. The study included 280 ...

  19. Fewer Advanced Alzheimer's Patients on Feeding Tubes

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_160456.html Fewer Advanced Alzheimer's Patients on Feeding Tubes Practice dropped by half ... organizations -- is declining, a new study finds. One Alzheimer's expert who reviewed the new findings was heartened ...

  20. Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study.

    LENUS (Irish Health Repository)

    Hampel, Harald

    2012-02-01

    OBJECTIVE: Lithium, a first-line drug for the treatment of bipolar depression, has recently been shown to regulate glycogen synthase kinase-3 (GSK-3), a kinase that is involved in the phosphorylation of the tau protein. Since hyperphosphorylation of tau is a core pathological feature in Alzheimer\\'s disease, lithium-induced inhibition of GSK-3 activity may have therapeutic effects in Alzheimer\\'s disease. In the current study, we tested the effect of short-term lithium treatment in patients with Alzheimer\\'s disease. METHOD: A total of 71 patients with mild Alzheimer\\'s disease (Mini-Mental State Examination score > or = 21 and < or = 26) were successfully randomly assigned to placebo (N = 38) or lithium treatment (N = 33) at 6 academic expert memory clinics. The 10-week treatment included a 6-week titration phase to reach the target serum level of lithium (0.5-0.8 mmol\\/L). The primary outcome measures were cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) and GSK-3 activity in lymphocytes. Secondary outcome measures were CSF concentration of total tau and beta-amyloid(1-42) (Abeta(1-42)), plasma levels of Abeta(1-42), Alzheimer\\'s Disease Assessment Scale (ADAS)-Cognitive summary scores, MMSE, and Neuropsychiatric Inventory (NPI). Patients were enrolled in the study from November 2004 to July 2005. RESULTS: No treatment effect on GSK-3 activity or CSF-based biomarker concentrations (P > .05) was observed. Lithium treatment did not lead to change in global cognitive performance as measured by the ADAS-Cog subscale (P = .11) or in depressive symptoms. CONCLUSIONS: The current results do not support the notion that lithium treatment may lead to reduced hyperphosphorylation of tau protein after a short 10-week treatment in the Alzheimer\\'s disease target population. TRIAL REGISTRATION: (Controlled-Trials.com) Identifier: ISRCTN72046462.

  1. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

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

  2. Maternal genetic mutations as gestational and early life influences in producing psychiatric disease-like phenotypes in mice

    Directory of Open Access Journals (Sweden)

    Georgia eGleason

    2011-05-01

    Full Text Available Risk factors for psychiatric disorders have traditionally been classified as genetic or environmental. Risk (candidate genes, although typically possessing small effects, represent a clear starting point to elucidate downstream cellular/molecular pathways of disease. Environmental effects, especially during development, can also lead to altered behavior and increased risk for disease. An important environmental factor is the mother, demonstrated by the negative effects elicited by maternal gestational stress and altered maternal care. These maternal effects can also have a genetic basis (e.g. maternal genetic variability and mutations. The focus of this review is maternal genotype effects that influence the emotional development of the offspring resulting in life-long psychiatric disease-like phenotypes. We have recently found that genetic inactivation of the serotonin1A receptor (5-HT1AR and the fmr-1 gene (encoding the fragile X mental retardation protein in mouse dams results in psychiatric disease-like phenotypes in their genetically unaffected offspring. 5-HT1AR deficiency in dams results in anxiety and increased stress responsiveness in their offspring. Mice with 5-HT1AR deficient dams display altered development of the hippocampus, which could be linked to their anxiety-like phenotype. Maternal inactivation of fmr-1, like its inactivation in the offspring, results in a hyperactivity-like condition and is associated with receptor alterations in the striatum. These data indicate a high sensitivity of the offspring to maternal mutations and suggest that maternal genotype effects can increase the impact of genetic risk factors in a population by increasing the risk of the genetically normal offspring as well as by enhancing the effects of offspring mutations.

  3. Neurochemical imaging of Alzheimer`s disease and other degenerative dementias

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.A.; Minoshima, S.; Kuhl, D.E. [Ann Arbor, Univ. of Michigan, MI (United States). Dept. of Internal Medicine. Division of Nuclear Medicine

    1998-09-01

    A wide variety of neurochemical and functional imaging approaches have been applied to the study of progressive dementias, particularly Alzheimer`s disease (Ad) and related disorders. Despite considerable progress in the past decade, the cause(s) of most cases of Ad remain undetermined and preventive or protective therapies are lacking. Specifically-designed imaging procedures have permitted the testing of pathophysiological hypotheses of the etiology and progression of Ad, and have yielded important insights in several areas including the potential roles of cerebral cortical cholinergic lesions, cellular inflammation, and losses of cortical synapses. From the perspective of clinical diagnosis, PET glucose metabolism imaging with use of ({sup 18}F)2-fluorodeoxyglucose (FDG) is the most sensitive and specific imaging modality yet identified. The overall performance of PET FDG is favorable for routine clinical evaluation of suspected Ad, and will likely gain increasing utilization in the near future. Assessments of glucose metabolism and other, specific aspects of neurochemistry in Ad will provide direct measures of therapeutic drug actions and may permit distinction of symptomatic versus disease-modifying therapies as they are developed and introduced in clinical trials.

  4. Longitudinal morphometric MRI study of Alzheimer's disease

    International Nuclear Information System (INIS)

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

  5. Nonliteral language in Alzheimer dementia: a review.

    Science.gov (United States)

    Rapp, Alexander M; Wild, Barbara

    2011-03-01

    The use of nonliteral language in clinical assessment, especially testing the patients' ability to interpret proverbs, has a long tradition in psychiatry. However, its diagnostic sensitivity and specificity in dementias is not yet clear. The aim of this review article is to examine the current evidence on nonliteral/figurative language (proverb, metaphor, metonymy, idiom, irony, sarcasm) comprehension in Alzheimer's disease and related disorders. A comprehensive literature search identified 25 studies (16 proverb, 3 metaphor, 0 metonymy, 5 idiom, 3 sarcasm) on nonliteral language comprehension in dementia. Studies predominantly indicate a deficit. Most studies investigated Alzheimer's dementia. Applied correctly, nonliteral language is a worthwhile diagnostic tool to evaluate language and abstract thinking in dementias. During assessment, familiarity testing (e.g., by asking "are you familiar with the proverb XY") is obligatory. Still, future research is needed in several areas: evidence on decline of nonliteral language over the course of the illness is limited. So far, almost no studies delineated proverb comprehension in high risk populations such as patients with mild cognitive impairment. Currently, there is a lack of studies addressing performance in direct comparison to relevant differential diagnosis like older-age depression, delirium, brain lesion, or other psychiatric conditions. PMID:21241530

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

    Science.gov (United States)

    Doraiswamy, P Murali; Xiong, Glen L

    2006-01-01

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

  7. Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics.

    Science.gov (United States)

    Sala Frigerio, Carlo; De Strooper, Bart

    2016-07-01

    Ten years of remarkable progress in understanding the fundamental biochemistry of Alzheimer's disease have been followed by ten years of remarkable and increasing clinical insight into the natural progression of the disorder. The concept of a long, intermediary, prodromal phase between the first appearance of amyloid plaques and tangles and the manifestation of dementia is now well established. The major challenge for the next decade is to chart the many cellular processes that underlie this phase and link the biochemical alterations to the clinical manifestation of Alzheimer's disease. We discuss here how genetics, new cell culture systems, and improved animal models will fuel this work. We anticipate that the resulting novel insights will provide a basis for further drug development for this terrible disease. PMID:27050320

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

    Science.gov (United States)

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

    2012-07-01

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

  9. INTELLIGENT TOOLS FOR PREDICTING ANXIETY OF ALZHEIMER'S PATIENTS

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To predict the incidence of anxiety in Alzheimer's disease (AD) patients by using machine-learning models. Methods A large randomized controlled clinical trial was analyzed in this study, which involved AD patients and caregivers from 6 different sites in the United States. The incidence of anxiety in AD patients was predicted by backpropagation artificial neural networks and several machine learning models, including Bayesian Networks, logistic regression, ADTree, J48, and Decision table. Results Among all models for predicting the incidence of anxiety in AD patients, the artificial neural network with respectively 6 and 3 neurons in the first and second hidden layers achieved the highest predictive accuracy of 85.56 %. The decision tree revealed three main risk factors: "caregiver experiencing psychological distress", "caregiver suffering from chronic disease or cancer", and "lack of professional care service". Conclusion The unique ability of artificial neural networks on classifying nonlinearly separable problems may substantially benefit the prediction, prevention and early intervention of anxiety in Alzheimer's patients. Decision tree has the double efficacy of predicting the incidence and discovering the risk factors of anxiety in Alzheimer's patients. More resources should be provided to caregivers to improve their mental and physical health, and more professional care services should be adopted by Alzheimer's families.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2009-02-01

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

  12. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza

    2014-03-01

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

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

    Science.gov (United States)

    Shinagawa, Shunichiro

    2016-05-01

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

  14. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  15. Research progress on animal models of Alzheimer's disease

    OpenAIRE

    Dong, Wen; Wang, Rong

    2015-01-01

    Alzheimer's disease (AD) is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

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

    OpenAIRE

    Ganguli, Mary; Kukull, Walter A.

    2010-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

  18. Inter-observer variation of diagnosis of Alzheimer's disease by SPECT

    International Nuclear Information System (INIS)

    SPECT shows characteristic distribution in Alzheimer's disease. The purpose of this study is to define inter-observer variations in the diagnosis of Alzheimer's disease. Fifty-seven patients, included 19 Alzheimer's disease were collected from four institutions. Five-graded score was used to interprete SPECT in 18 regions. Ten nuclear medicine physicians interpreted SPECT referred with MMSE and clinical information. Among 57 cases 19 Alzheimer's disease were selected in this study. Statistics were performed between SPECT score and MMSE score. In conclusion, inter-observer variation is present in SPECT interpretation. There was a good correlation SPECT and MMSE with proper brain SPECT physicians. They are superior to in the interpretation not only resident, but other specialists. Education in the interpretation of brain SPECT looks important. (author)

  19. Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia.

    Science.gov (United States)

    Ganske, Steffi; Haussmann, Robert; Gruschwitz, Antonia; Werner, Annett; Osterrath, Antje; Baumgaertel, Johanna; Lange, Jan; Donix, Katharina L; Linn, Jennifer; Donix, Markus

    2016-08-01

    A first-degree family history of Alzheimer's disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer's disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer's disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer's disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease. PMID:27303063

  20. mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

    Science.gov (United States)

    Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

    2014-08-01

    Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain. PMID:25003233

  1. In vivo amyloid imaging in Alzheimer's disease

    International Nuclear Information System (INIS)

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

  2. Cerebral imaging revealing Alzheimer's disease

    International Nuclear Information System (INIS)

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

  3. Domain adaptation for Alzheimer's disease diagnostics.

    Science.gov (United States)

    Wachinger, Christian; Reuter, Martin

    2016-10-01

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

  4. 精神科记忆门诊阿尔茨海默病患者的精神行为症状%Characteristics of neuropsychiatric symptoms among individuals with Alzheimer's disease in a memory clinic setting

    Institute of Scientific and Technical Information of China (English)

    张美燕; 王华丽; 李涛; 于欣

    2011-01-01

    Objective: To investigate the characteristics and related factors of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD). Methods: Totally 129 AD patients who had completed the neuropsychological and neurobehavioral assessments were included in this analysis. NPS were assessed with the Neuropsychiatric Inventory (NPI). The cognitive function was assessed with the Mini-Mental State Examination (MMSE) and Alzheimer Disease Assessment Scale-Cognitive portion (ADAS-Cog). The functional status was assessed with the Activities of Daily Living (ADL). According to the MMSE score, AD patients were classified into mild (MMSE ≥20, n= 46),moderate (MMSE= 11 ~ 19, n= 59), and severe ( MMSE ≤ 10, n= 24) cases. Factor analysis was used to examine the features of NPS in AD, and ANOVA was used for group comparisons. Results: ( 1 ) Factor analysis identified three symptom clusters in AD patients, including psychosis, frontal dysfunction and mood syndrome. The total scores and the sub-scores of psychosis and frontal dysfunction of NPI were higher in severe AD group than in mild and moderate AD groups ( e. g., the scores of psychotic syndrome, (21.4 ± 13.4) vs. ( 10. 5 ± 7.9), ( 14. 0 ± 10. 1),Ps < 0. 05). The scores of mood syndrome was not significantly different among the three AD groups (Ps > 0. 05).(2) There were significant positive correlation between the factor scores of psychosis, frontal dysfunction syndrome of NPI with the factor scores of memory, language, praxia, attention of ADAS-Cog as well as with ADL score ( r=0. 28 ~ 0. 47, P < 0. 05). The factor score of mood syndrome of NPI were positively correlated with the factor scores of language and praxis of ADAS-Cog (r= 0. 19, 0. 24, Ps < 0. 05). Conclusion: The neuropsychiatric symptoms in Alzheimer's disease may be characterized by psychosis, frontal dysfunction and mood syndrome. The frequency and severity of neuropsychiatric symptoms can increase with the severity of Alzheimer's disease. In

  5. Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease

    OpenAIRE

    Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael; Ding, Jinhui; Lupton, Michelle K.; Troakes, Claire; Al-Sarraj, Safa; Niblock, Michael; Gallo, Jean-Marc; Adnan, Jihad; Killick, Richard; Brown, Kristelle S.; Medway, Christopher; Lord, Jenny; Turton, James

    2014-01-01

    The overlapping clinical and neuropathologic features between late-onset apparently sporadic Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and other neurodegenerative dementias (frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jakob disease) raise the question of whether shared genetic risk factors may explain the similar phenotype among these disparate disorders. To investigate this intriguing hypothesis, we analyzed rare c...

  6. {sup 1}H-MR-spectroscopic imaging in patients with Alzheimer`s disease; {sup 1}H-MR-spektroskopische Bildgebung bei Patienten mit klinisch gesichertem Morbus Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Block, W. [Radiogische Klinik der Univ. Bonn (Germany); Traeber, F. [Radiogische Klinik der Univ. Bonn (Germany); Kuhl, C.K. [Radiogische Klinik der Univ. Bonn (Germany); Fric, M. [Psychiatrische Universitaetsklinik, Bonn (Germany); Keller, E. [Radiogische Klinik der Univ. Bonn (Germany); Lamerichs, R. [Philips Medical Systems, Best (Netherlands); Rink, H. [Radiogische Klinik der Univ. Bonn (Germany); Moeller, H.J. [Psychiatrische Universitaetsklinik, Bonn (Germany); Schild, H.H. [Radiogische Klinik der Univ. Bonn (Germany)

    1995-09-01

    To detect regional differences in accompanying metabolic changes, {sup 1}H-Magnetic Resonance Spectroscopic Imaging was performed in 16 patients with Alzheimer`s disease (AD); the clinical diagnosis was based upon DSM-III-R and NINCDS-ADRDA guidelines. In the hippocampal region metabolic maps of the local distribution of N-acetylaspartate (NAA), choline (Cho), creatine compounds (P(Cr)) and lactate were determined. Ratios of Cho/NAA, (P)Cr/NAA and Cho/(P)Cr calculated from selected hippocampal spectra were compared to those from healthy volunteers (n=17). AD patients demonstrated an increase of Cho/NAA and (P)Cr/NAA ratios caused by increased choline compounds and decreased NAA. These alterations were observed in 11/12 cases in the hippocampal and in 7/12 in the temporo-occipital region. Hippocampal Cho/NAA ratios (0.56{+-}0.19) were significantly elevated compared with controls. The observed elevation of choline compounds in the hippocampus supports the hypothesis that alterations in the cholinergic system play an important role in Alzheimer`s disease. The observed reduction of NAA is due to neuronal degeneration. (orig./MG) [Deutsch] Zur Darstellung von regionalen metabolischen Veraenderungen bei Morbus Alzheimer wurden mit dem Verfahren des {sup 1}H-Magnetic-Resonance-Spectroscopic-Imaging 16 Patienten untersucht, deren Diagnose klinisch entsprechend DSM-III-R- und NINCDS-ADRDA-Kriterien gestellt wurde. In Hoehe des Hippocampus wurden transaxiale ``Metabolitenkarten`` der regionalen Verteilung von N-Acetyl-Aspartat (NAA), cholinhaltiger Verbindungen (Cho), Gesamtkreatin (P(Cr)) und Laktat erstellt. Zur Quantifizierung der Unterschiede zum Normalkollektiv (n=17) wurden die Metabolitenquotienten Cho/NAA, (P)Cr/NAA und Cho/(P)Cr, insbesondere aus der Hippocampusregion, ermittelt. Das Krankheitsbild des M. Alzheimer stellte sich durch eine Erhoehung der Quotienten Cho/NAA und Cho/(P)Cr dar, wobei neben einer Cholinerhoehung die Reduktion des Neurotransmitters NAA

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

    Science.gov (United States)

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

  8. Participating in Alzheimer's Research: For Yourself and Future Generations

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  15. Characteristics of clinical features and related evaluation of Alzheimer disease and vascular dementia%阿尔茨海默病与血管性痴呆的临床及相关检查特点分析

    Institute of Scientific and Technical Information of China (English)

    潘永惠; 段淑荣; 赵庆杰

    2005-01-01

    disease (AD) and vascular dementia (VD),the two major types of dementia in old age, differ from each other in pathological mechanism, treatment and prognosis. Up to now, no effective therapeutic method for AD is available, but VD can be treated effectively so that patients' quality of life can be improved.OBJECTIVE: To investigate the clinical features of brain electrical activity mapping (BEAM) and brain evoked potentials (BEP) between AD and VD patients.DESIGN: Retrospective analysis based on AD and VD patients.SETTING: Neurological Department, the First Clinical Medical College of Harbin Medical University.PARTICIPANTS: All inpatients and discharged patients were selected filiated to Harbin Medical University from December 1996 to December 2000. The history was provided by the patients themselves or their relatives who lived together with them. Nine cases of AD and fourteen cases of VD were diagnosed according to the diagnostic standard for AD and VD set by the National Institute of Neurological and Communicative Disorder and Stroke-the Alzheimer disease and Related Disorder Association, and Chinese Classification and Diagnostic Criteria of Mental Disease (4th edition). According to the clinical rating standard, the patients had mild or moderate degree of dementia.METHODS: AD and VD patients were analyzed with retrospective analynitive functions, including long-term and short-term memory, calculation,comprehension, abstract thinking, dyschronism and disorientation; c. emotional reaction, including depression, anxiety, fear, euphoria, compulsive laughing and crying; d personality alteration, including indifference,optimally were collected from the abnormal segment signals. After calculation, 4 frequency band powers of θ,δ, α and β of the total power of 1-30 N1, P2, N2 and P3 and the waves of P2 and P3 were measured. Comparison between the two groups and rate comparison were made with t-test and χ2 test, respectively.ease, cognitive functions and noncognitive

  16. Benzyl-N-acetyl-alpha-D-galactosaminide induces a storage disease-like phenotype by perturbing the endocytic pathway.

    Science.gov (United States)

    Ulloa, Fausto; Real, Francisco X

    2003-04-01

    The sugar analog O-benzyl-N-acetyl-alpha-d-galactosaminide (BG) is an inhibitor of glycan chain elongation and inhibits alpha2,3-sialylation in mucus-secreting HT-29 cells. Long-term exposure of these cells to BG is associated with the accumulation of apical glycoproteins in cytoplasmic vesicles. The mechanisms involved therein and the nature of the vesicles have not been elucidated. In these cells, a massive amount of BG metabolites is synthesized. Because sialic acid is mainly distributed apically in epithelial cells, it has been proposed that the BG-induced undersialylation of apical membrane glycoproteins is responsible for their intracellular accumulation due to a defect in anterograde traffic and that sialic acid may constitute an apical targeting signal. In this work, we demonstrate that the intracellular accumulation of membrane glycoproteins does not result mainly from defects in anterograde traffic. By contrast, in BG-treated cells, endocytosed membrane proteins were retained intracellularly for longer periods of time than in control cells and colocalized with accumulated MUC1 and beta(1) integrin in Rab7/lysobisphosphatidic acid(+) vesicles displaying features of late endosomes. The phenotype of BG-treated cells is reminiscent of that observed in lysosomal storage disorders. Sucrose induced a BG-like, lysosomal storage disease-like phenotype without affecting sialylation, indicating that undersialylation is not a requisite for the intracellular accumulation of membrane glycoproteins. Our findings strongly support the notion that the effects observed in BG-treated cells result from the accumulation of BG-derived metabolites and from defects in the endosomal pathway. We propose that abnormal subcellular distribution of membrane glycoproteins involved in cellular communication and/or signaling may also take place in lysosomal storage disorders and may contribute to their pathogenesis. PMID:12538583

  17. Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect

    KAUST Repository

    Demetrius, Lloyd A.

    2015-01-14

    Epidemiological and biochemical studies show that the sporadic forms of Alzheimer\\'s disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.

  18. Challenges, solutions, and recommendations for Alzheimer's disease combination therapy.

    Science.gov (United States)

    Hendrix, James A; Bateman, Randall J; Brashear, H Robert; Duggan, Cynthia; Carrillo, Maria C; Bain, Lisa J; DeMattos, Ronald; Katz, Russell G; Ostrowitzki, Susanne; Siemers, Eric; Sperling, Reisa; Vitolo, Ottavio V

    2016-05-01

    Given the complex neuropathology Alzheimer's disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer's Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders. PMID:27017906

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    Episodic memory tests that measure cued recall may be particularly effective in the diagnosis of early Alzheimer's disease (AD) because they examine both episodic and semantic memory functions. The Category Cued Recall (CCR) test provides superordinate semantic cues at encoding and retrieval, and...... high discriminative validity has been claimed for this test. The aim of this study was to investigate the discriminative validity for this test when compared with the 10-word memory list from Alzheimer's Disease Assessment Scale (ADAS-cog) that measures free recall. The clinical diagnosis of AD was...... taken as the standard. It was also investigated whether the two episodic memory tests correlated with measures of semantic memory. The tests were administered to 35 patients with very mild AD (Mini Mental State Examination score > 22) and 28 control subjects. Both tests had high sensitivity (>88%) with...

  20. Purinergic receptors as potential therapeutic targets in Alzheimer's disease.

    Science.gov (United States)

    Woods, Lucas T; Ajit, Deepa; Camden, Jean M; Erb, Laurie; Weisman, Gary A

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive loss of memory and cognitive ability and is a serious cause of mortality. Many of the pathological characteristics associated with AD are revealed post-mortem, including amyloid-β plaque deposition, neurofibrillary tangles containing hyperphosphorylated tau proteins and neuronal loss in the hippocampus and cortex. Although several genetic mutations and risk factors have been associated with the disease, the causes remain poorly understood. Study of disease-initiating mechanisms and AD progression in humans is inherently difficult as most available tissue specimens are from late-stages of disease. Therefore, AD researchers rely on in vitro studies and the use of AD animal models where neuroinflammation has been shown to be a major characteristic of AD. Purinergic receptors are a diverse family of proteins consisting of P1 adenosine receptors and P2 nucleotide receptors for ATP, UTP and their metabolites. This family of receptors has been shown to regulate a wide range of physiological and pathophysiological processes, including neuroinflammation, and may contribute to the pathogenesis of neurodegenerative diseases like Parkinson's disease, multiple sclerosis and AD. Experimental evidence from human AD tissue has suggested that purinergic receptors may play a role in AD progression and studies using selective purinergic receptor agonists and antagonists in vitro and in AD animal models have demonstrated that purinergic receptors represent novel therapeutic targets for the treatment of AD. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:26519903

  1. The Role of Cdk5 in Alzheimer's Disease.

    Science.gov (United States)

    Liu, Shu-Lei; Wang, Chong; Jiang, Teng; Tan, Lan; Xing, Ang; Yu, Jin-Tai

    2016-09-01

    Alzheimer's disease (AD) is known as the most fatal chronic neurodegenerative disease in adults along with progressive loss of memory and other cognitive function disorders. Cyclin-dependent kinase 5 (Cdk5), a unique member of the cyclin-dependent kinases (Cdks), is reported to intimately associate with the process of the pathogenesis of AD. Cdk5 is of vital importance in the development of CNS and neuron movements such as neuronal migration and differentiation, synaptic functions, and memory consolidation. However, when neurons suffer from pathological stimuli, Cdk5 activity becomes hyperactive and causes aberrant hyperphosphorylation of various substrates of Cdk5 like amyloid precursor protein (APP), tau and neurofilament, resulting in neurodegenerative diseases like AD. Deregulation of Cdk5 contributes to an array of pathological events in AD, ranging from formation of senile plaques and neurofibrillary tangles, synaptic damage, mitochondrial dysfunction to cell cycle reactivation as well as neuronal cell apoptosis. More importantly, an inhibition of Cdk5 activity with inhibitors such as RNA inference (RNAi) could protect from memory decline and neuronal cell loss through suppressing β-amyloid (Aβ)-induced neurotoxicity and tauopathies. This review will briefly describe the above-mentioned possible roles of Cdk5 in the physiological and pathological mechanisms of AD, further discussing recent advances and challenges in Cdk5 as a therapeutic target. PMID:26227906

  2. The Importance of Adipokines in Alzheimer's Disease

    OpenAIRE

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

    2015-01-01

    Dementia and Alzheimers disease are characterized by disturbances in brain function and structure. Similarly, body mass index and obesity are associated with certain brain pathologies, including Alzheimers disease and dementia. In fact, there is mounting evidence linking metabolic dysfunction with dementia and Alzheimers disease. Major endocrine axes constitute links between brain and peripheral tissues, especially adipose tissue. Adipose tissue is metabolically very active and produces a var...

  3. Calcium channel blockers and Alzheimer's disease★

    OpenAIRE

    Tan, Yi; Deng, Yulin; Qing, Hong

    2012-01-01

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

  4. AD患者血浆Leptin和血清Hcy、S100B、NSE联合检测的临床意义%Clinical Significance of Determination of Plasma Leptin and Serum Hcy, S100B and NSE Levels in Patients with Alzheimer Disease

    Institute of Scientific and Technical Information of China (English)

    窦焕芝; 卢萌

    2011-01-01

    探讨阿尔茨海默病(AD)患者血浆Leptin和血清Hcy、S100B、NSE水平的变化及临床意义.应用RIA和CLIA法测定32例AD患者血浆Leptin和血清Hcy、S100B、NSE水平,并与30名正常组作比较.结果表明AD患者血浆Leptin和血清Hcy、S100B、NSE水平与正常组比较,均有非常显著地升高(P<0.01),且Leptin水平与Hcy、S100B、NSE水平呈相关(r=0.5982、0.4762、0.6014,P<0.01).检测AD患者血浆Leptin和血清Hcy、S100B、NSE水平对判断病情和评价疗效,均具有一定的临床价值.%To explore the clinical significance of changes of plasma leptin and serun Hcy, Sl00B and NSE levels in patients with Alzheimer Disease (AD). The plasma leptin and serum NSE levels in 32 AD patients and 30 controls were determined by using RIA, and the serum Hcy and Sl00B levels were measured by using CLIA.The results showed that the plasma leptin and serun Hcy, S100B and NSE levels in AD patients were significantly higher than these in controls (P <0.01 ). The plasma leptin levels in AD patients was mutually positively correlated with serum Hcy, Sl00B and NSE levels (r =0. 5982, 0.4762, 0.6014, P <0. 0l ). The detection of plasma leptin and serum Hcy, S100B and NSE levels may be helpful for the prediction of treatment efficiency in patients with Alzheimer disease.

  5. Estado nutricional na doença de Alzheimer Nutritional status in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jacqueline Machado

    2009-01-01

    Full Text Available OBJETIVO: Descrever aspectos nutricionais de idosos com doença de Alzheimer leve a moderada em ambulatório. MÉTODOS: A amostra contou com a participação de 40 idosos de ambos os sexos, diagnosticados com doença da Alzheimer (NINCDS-ADRDA por seleção consecutiva. Foram realizadas avaliações socioeconômicas de atividades de vida diária, antropométrica, clínica e dietética. RESULTADOS: Do total, 65% eram do sexo feminino. Ao se verificar a capacidade funcional, constatou-se que mais de 70% dos idosos mostraram-se independentes para a realização de suas atividades de vida diária. Com base na avaliação do estado nutricional e na gravidade da doença, os idosos encontraram-se eutróficos, com diferença estatisticamente significativa na circunferência do braço entre os graus de demência. Quanto à presença de enfermidades secundárias à doença, 52% dos idosos apresentaram hipertensão arterial sistêmica, seguido de alterações do tipo artrose (17%. O consumo médio de energia e de macronutrientes dos idosos classificados no estágio leve foi de 1645 kcal, distribuídos em 53,7% para carboidratos, 17,5% para proteínas e 28,8% para lipídeos, enquanto que aqueles no estágio moderado foi de 1482 kcal, distribuídos em 59,3% para carboidratos, 16,1% para proteínas e 24,6% para lipídeos. CONCLUSÃO: Neste estudo descritivo de uma amostra ambulatorial de idosos com DA leve e moderada a maior parte deles apresentou estado nutricional de eutrofia, com consumo dietético adequado de carboidratos, proteínas, lipídeos e vitamina C, embora com baixo consumo alimentar de vitamina E.OBJECTIVE: To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. METHODS: Subjects of both genders (n=40 diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary

  6. Single photon emission computed tomography in the diagnosis of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hanyu, Haruo; Asano, Tetsuichi; Abe, Shin`e; Arai, Hisayuki; Iwamoto, Toshihiko; Takasaki, Masaru; Shindo, Hiroaki; Abe, Kimihiko [Tokyo Medical Coll. (Japan)

    1997-06-01

    Studies with single photon emission computed tomography (SPECT) have shown temporoparietal (TP) hypoperfusion in patients with Alzheimer`s disease (AD). We evaluated the utility of this findings in the diagnosis of AD. SPECT images with {sup 123}I-iodoamphetamine were analyzed qualitatively by a rater without knowledge of the subject`s clinical status. Sixty-seven of 302 consecutive patients were judged as having TP hypoperfusion by SPECT imaging. This perfusion pattern was observed in 44 of 51 patients with AD, in 5 with mixed dementia, 8 with cerebrovascular disease (including 5 with dementia), 4 with Parkinson`s disease (including 2 with dementia), 1 with normal pressure hydrocephalus, 1 with slowly progressive aphasia, 1 with progressive autonomic failure, 2 with age-associated memory impairment, and 1 with unclassified dementia. The sensitivity for AD was 86.3% (44 of 51 AD), and the specificity was 91.2% (229 of 251 non-AD). Next, we looked for differences in perfusion images between patients with AD and without AD. Some patients without AD had additional hypoperfusion beyond TP areas: deep gray matter hypoperfusion and diffuse frontal hypoperfusion, which could be used to differentiate them from the patients with AD. Others could not be distinguished from patients with AD by their perfusion pattern. Although patients with other cerebral disorders occasionally have TP hypoperfusion, this finding makes the diagnosis of AD very likely. (author)

  7. Endocannabinoid signalling in Alzheimer's disease.

    Science.gov (United States)

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

    2013-12-01

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

  8. Alzheimer's Disease and Vitamin E

    OpenAIRE

    Empey, Matthew

    1998-01-01

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

  9. Inflammatory process in Alzheimer's Disease

    OpenAIRE

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

    2013-01-01

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

  10. Immunotherapeutic Approaches to Alzheimer's Disease

    Science.gov (United States)

    Monsonego, Alon; Weiner, Howard L.

    2003-10-01

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

  11. The influence of parental history of Alzheimer's disease and apolipoprotein E ε4 on the BOLD signal during recognition memory

    OpenAIRE

    Xu, Guofan; McLaren, Donald G.; Ries, Michele L.; Fitzgerald, Michele E.; Barbara B. Bendlin; Howard A. Rowley; Sager, Mark A.; Atwood, Craig; Asthana, Sanjay; Johnson, Sterling C.

    2008-01-01

    First-degree family history (FH) of sporadic Alzheimer's disease and the apolipoprotein E ε4 allele (APOE4) are risk factors for Alzheimer's disease that may affect brain function prior to onset of clinical symptoms. In this functional MRI (fMRI) study, we used an episodic recognition task that required discrimination of previously viewed (PV) and novel (NV) faces to examine differences in blood oxygen level dependent (BOLD) signal due to risk factors in 74 middle-aged cognitively normal indi...

  12. Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center.

    Science.gov (United States)

    Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E; Frosch, Matthew P; Betensky, Rebecca A; Hyman, Bradley T

    2013-12-01

    To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating-Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. PMID:24226270

  13. Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies

    OpenAIRE

    Crespi, Gabriela A. N.; Hermans, Stefan J.; Parker, Michael W.; Luke A. Miles

    2015-01-01

    Solanezumab (Eli Lilly) and crenezumab (Genentech) are the leading clinical antibodies targeting Amyloid-β (Aβ) to be tested in multiple Phase III clinical trials for the prevention of Alzheimer's disease in at-risk individuals. Aβ capture by these clinical antibodies is explained here with the first reported mid-region Aβ-anti-Aβ complex crystal structure. Solanezumab accommodates a large Aβ epitope (960 Å2 buried interface over residues 16 to 26) that forms extensive contacts and hydrogen b...

  14. Alzheimer disease immunotherapeutics: then and now.

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Tabira, Takeshi

    2016-03-01

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

  16. Spatial Navigation in Preclinical Alzheimer's Disease.

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    Mega, M.; Lee, L.; Dinov, I.; Mishkin, F.; Toga, A.; Cummings, J.

    2000-01-01

    BACKGROUND—Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities.
OBJECTIVES—To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT).
METHODS—Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map.
RESULTS—The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group.
CONCLUSION—Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

 PMID:10896687

  18. Role of melatonin in Alzheimer-like neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Jian-zhi WANG; Ze-fen WANG

    2006-01-01

    Alzheimer disease (AD), an age-related neurodegenerative disorder with progressive loss of memory and deterioration of comprehensive cognition, is characterized by extracellular senile plaques of aggregated β-amyloid (Aβ), and intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent studies showed that melatonin, an indoleamine secreted by the pineal gland, may play an important role in aging and AD as an antioxidant and neuroprotector.Melatonin decreases during aging and patients with AD have a more profound reduction in this hormone. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning, and slows down the progression of cognitive impairment in Alzheimer's patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties: it not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our recent studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood,a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting cholinergic neurons and in anti-inflammation. Here, the neuroprotective effects of melatonin and the underlying mechanisms by which it exerts its effects are reviewed. The capacity of melatonin to prevent or ameliorate tau and Aβ pathology further enhances its potential in the prevention or treatment of AD.

  19. NEUROPSYCHOLOGICAL ASSESSMENT IN THE ALZHEIMER DISEASE: EPISODIC AND SEMANTIC MEMORY

    Directory of Open Access Journals (Sweden)

    Ana Comesaña

    2009-12-01

    Full Text Available This paper aims to review the neuropsychological evaluation process in Alzheimer (AD patients, specifically that related to episodic and semantic memory. Alzheimer-style dementia is the main form of dementia, and is nowadays one of the most important social, cultural and health-related problems. Diagnosis and differentiation from normal aging are difficult in the initial stages, and so neuropsychological evaluation is key. The criteria currently utilized are those of the DSM IV (American Psychiatric Association, 1994 and of the NINCDS-ADRDA (Instituto Nacional para los Desórdenes Neurológicos, de la Comunicación y el Accidente Cerebro Vascular y la Asociación para la Enfermedad de Alzheimer y Desórdenes Relacionados (McKhann G, Drachman D, Folstein M, y col., 1984, and they require that the diagnosis of probable AD be confirmed by neuropsychological evaluation in addition to clinical evaluation and other studies. After the division of long term memory into semantic and episodic memory was made, specific tests were created for their neuropsychological evaluation in different pathologies, including AD. An important contribution to the early detection of memory deterioration typical of such illness was thus made.

  20. Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.

    Science.gov (United States)

    Trojano, Luigi; Gainotti, Guido

    2016-04-21

    Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing. PMID:27104898

  1. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    Science.gov (United States)

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning. PMID:18674439

  2. Alzheimer disease: presenilin springs a leak

    OpenAIRE

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

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  4. The Importance of Adipokines in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seyid Ahmet Ay

    2015-06-01

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

  5. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.

    Science.gov (United States)

    Bauer, Ryan; Janowska, Katarzyna; Taylor, Kelly; Jordan, Brad; Gann, Steve; Janowski, Tomasz; Latimer, Ethan C; Matsushita, Osamu; Sakon, Joshua

    2015-03-01

    Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 Å resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 Å resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, Rfree = 21.2%; 1.6 Å resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also

  6. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

    Science.gov (United States)

    2012-02-24

    ... HUMAN SERVICES Draft National Plan To Address Alzheimer's Disease AGENCY: Office of the Assistant.... SUMMARY: HHS is soliciting public input on the draft National Plan to Address Alzheimer's Disease, which... Alzheimer's disease. Coordinate Alzheimer's disease research and services across all federal...

  7. Goal setting and attainment in Alzheimer's disease patients treated with donepezil

    OpenAIRE

    Rockwood, K; Graham, J; Fay, S.

    2002-01-01

    Objectives: To understand the treatment goals of Alzheimer's disease (AD) patients, carers, and physicians; to estimate whether clinically important goals are met during treatment with donepezil; and to compare a measure of goal attainment with standard measures used to evaluate AD treatment.

  8. Behavioral symptoms in mild cognitive impairment as compared with Alzheimer's disease and healthy older adults

    NARCIS (Netherlands)

    Van der Mussele, Stefan; Le Bastard, Nathalie; Vermeiren, Yannick; Saerens, Jos; Somers, Nore; Marien, Peter; Goeman, Johan; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2013-01-01

    BACKGROUND: Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aim of this study is to characterize behavior in MCI compared with Alzheimer's disease (AD) and healthy older patients. DESIGN

  9. Cognitive profiles and regional cerebral blood flow patterns in dementia of the Alzheimer type

    DEFF Research Database (Denmark)

    Waldemar, G; Bruhn, P; Schmidt, E;

    1994-01-01

    Individual cognitive profiles and correlations between cognitive functions and regional cerebral blood flow (rCBF) were analyzed in 20 consecutive patients with a clinical diagnosis of probable Alzheimer's disease (AD). CBF was measured with high resolution single photon emission computed...

  10. Oculomotor Function in Frontotemporal Lobar Degeneration, Related Disorders and Alzheimer's Disease

    Science.gov (United States)

    Garbutt, Siobhan; Matlin, Alisa; Hellmuth, Joanna; Schenk, Ana K.; Johnson, Julene K.; Rosen, Howard; Dean, David; Kramer, Joel; Neuhaus, John; Miller, Bruce L.; Lisberger, Stephen G.; Boxer, Adam L.

    2008-01-01

    Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were…

  11. Cerebrospinal fluid amyloid beta42/phosphorylated tau ratio discriminates between Alzheimer's disease and vascular dementia.

    NARCIS (Netherlands)

    Jong, D. de; Jansen, R.W.M.M.; Kremer, H.P.H.; Verbeek, M.M.

    2006-01-01

    BACKGROUND: The differentiation of Alzheimer's disease (AD) from vascular dementia (VaD) is hampered by clinical diagnostic criteria with disappointing sensitivity and specificity. The objective of this study was to investigate whether cerebrospinal fluid (CSF) levels of total tau protein (t-tau), a

  12. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutant...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-01

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

  15. Maternal Transmission of Alzheimer Disease

    OpenAIRE

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

    2012-01-01

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

  16. Tratamento farmacológico da doença de Alzheimer Pharmacological treatment of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Orestes V. Forlenza

    2005-06-01

    Full Text Available 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 grave, bem como as perspectivas de seu emprego em associação com os inibidores das colinesterases, são discutidos adicionalmente com base em achados clínicos e neurobiológicos. Discute-se o papel da reposição estrogênica, dos antioxidantes, das estatinas e dos antiinflamatórios no tratamento e na prevenção da demência, levando em consideração os resultados negativos oriundos de estudos clínico-epidemiológicos recentes. Finalmente, são apresentadas algumas perspectivas futuras do tratamento da doença de Alzheimer: entre as estratégias farmacológicas, que têm como objetivo modificar mecanismos patogênicos, são abordadas as diferentes modalidades da terapêutica antiamilóide, com destaque na imunoterapia da doença de Alzheimer.The current article provides a comprehensive overview of the current strategies and the future directions of the pharmacological treatment of Alzheimer's disease. The benefits and shortcomings of cholinergic replacement therapy is discussed in the light of its neurobiological, pharmacological and clinical data, illustrated by the most relevant randomised controlled trials and recent meta-analytical studies. The role of memantine in moderate to severe dementia, and the perspectives of combination therapy are further discussed both at clinical and neuro-pharmacological levels. In addition, the role of oestrogen replacement, antioxidants, statins, and non-steroidal anti-inflammatory drugs, in the

  17. Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease

    DEFF Research Database (Denmark)

    Ellefsen, Birita; Morse, Douglas E; Waldemar, Gunhild; Holm-Pedersen, Poul

    2012-01-01

    doi: 10.1111/j.1741-2358.2011.00560.x Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease Objective:  To identify indicators of root caries among persons with newly diagnosed Alzheimer's disease (AD). Background:  Few studies have investigated dental caries in...... older adults with AD. Previously we found that persons with AD had significantly more root caries compared to persons with dementia other than AD. Methods:  Participants were recruited from two university hospital clinics in Copenhagen, Denmark. A team of neurologists/geriatricians carried out the...

  18. Alzheimer's pathogenesis and its link to the mitochondrion.

    Science.gov (United States)

    Simoncini, C; Orsucci, D; Caldarazzo Ienco, E; Siciliano, G; Bonuccelli, U; Mancuso, M

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. This neurodegenerative disorder is clinically characterized by impairment of cognitive functions and changes in behaviour and personality. The pathogenesis of AD is still unclear. Recent evidence supports some role of mitochondria dysfunction and oxidative stress in the development of the neurodegenerative process. In this review, we discuss the role of mitochondrial dysfunction in AD, focusing on the mechanisms that lead to mitochondrial impairment, oxidative stress, and neurodegeneration, a "vicious circle" that ends in dementia. PMID:25973139

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

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Min-yue CHI

    2015-07-01

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

  1. Copper Modulation as a Therapy for Alzheimer's Disease?

    OpenAIRE

    Yasmina Manso; Gemma Comes; Juan Hidalgo; Bush, Ashley I.; Adlard, Paul A

    2011-01-01

    The role of metals in the pathophysiology of Alzheimer's disease (AD) has gained considerable support in recent years, with both in vitro and in vivo data demonstrating that a mis-metabolism of metal ions, such as copper and zinc, may affect various cellular cascades that ultimately leads to the development and/or potentiation of AD. In this paper, we will provide an overview of the preclinical and clinical literature that specifically relates to attempts to affect the AD cascade by the modul...

  2. Description of Lyme disease-like syndrome in Brazil: is it a new tick borne disease or Lyme disease variation?

    Directory of Open Access Journals (Sweden)

    E. Mantovani

    2007-04-01

    Full Text Available An emerging clinical entity that reproduces clinical manifestations similar to those observed in Lyme disease (LD has been recently under discussion in Brazil. Due to etiological and laboratory particularities it is named LD-like syndrome or LD imitator syndrome. The condition is considered to be a zoonosis transmitted by ticks of the genus Amblyomma, possibly caused by interaction of multiple fastidious microorganisms originating a protean clinical picture, including neurological, osteoarticular and erythema migrans-like lesions. When peripheral blood of patients with LD-like syndrome is viewed under a dark-field microscope, mobile uncultivable spirochete-like bacteria are observed. PCR carried out with specific or conservative primers to recognize Borrelia burgdorferi sensu stricto or the genus Borrelia has been negative in ticks and in biological samples. Two different procedures, respectively involving hematoxylin and eosin staining of cerebrospinal fluid and electron microscopy analysis of blood, have revealed spirochetes not belonging to the genera Borrelia, Leptospira or Treponema. Surprisingly, co-infection with microorganisms resembling Mycoplasma and Chlamydia was observed on one occasion by electron microscopy analysis. We discuss here the possible existence of a new tick-borne disease in Brazil imitating LD, except for a higher frequency of recurrence episodes observed along prolonged clinical follow-up.

  3. 2008 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2008-03-01

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

  4. Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Svensson Leif

    2002-09-01

    Full Text Available Abstract Background Mild cognitive impairment (MCI was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD. Regional cerebral blood flow (rCBF as measured by single photon emission computed tomography (SPECT was used to study the heterogeneity of MCI and to look for predictors of future development of AD. Methods rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO. An automated analysis software (BRASS was applied to analyze the relative blood flow (cerebellar ratios of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI and 37 subjects remained stable (SMCI. The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC analysis was applied for the discrimination of the two subgroups at baseline. Results The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%–76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. Conclusion A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD.

  5. Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

    Science.gov (United States)

    Femminella, Grazia D; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2016-01-01

    The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID:27189470

  6. Lifestyle Methods for Prevention of Alzheimer's Disease From the Perspective of Traditional Persian Medicine.

    Science.gov (United States)

    Tajadini, Haleh; Choopani, Rasool; Saifadini, Rostam

    2016-07-01

    Alzheimer's disease is considered as a major problem for society health since it affects interpersonal and social relationships. With regard to the global attention toward complementary medicine, search for preventive, diagnostic, and treatment strategies in complementary medicine schools such as the old dynamic doctrine of traditional Persian medicine seems to be necessary. In this type of medicine, description and analysis of the disease and preventive and treatment methods have great importance. The present study provides a useful classification of recommendations for prevention and control of Alzheimer's disease. Prevention is prior to the treatment and is easier and less costly. Recommendations mentioned in traditional Persian medicine texts for prevention of Alzheimer's disease provide fields of clinical and complementary studies for researches. PMID:26494860

  7. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease

    International Nuclear Information System (INIS)

    We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using 18F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices, while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis

  8. Genetic variations underlying Alzheimer's disease: evidence from genome-wide association studies and beyond.

    Science.gov (United States)

    Cuyvers, Elise; Sleegers, Kristel

    2016-07-01

    With the advent of genome-wide association studies (GWAS) and next-generation sequencing, more than 20 risk loci that affect Alzheimer's disease have been identified. These loci are estimated to explain about 28% of the heritability of liability, 30% of familial risk, and over 50% of sibling recurrence risk of developing Alzheimer's disease. These estimates are high in comparison with those for other complex diseases for which more risk loci have been discovered, such as type 2 diabetes, which is mostly a result of the strong effect of APOE ɛ4 and to a lesser extent the rare variant TREM2 p.Arg47His. The search for functionally relevant genetic variants in risk loci detected in GWAS has revealed that the genetic variations underlying Alzheimer's disease include common variants affecting expression and splicing, a functional intragenic copy number variation, and rare pathogenic variants in risk loci, some of which might lead to familial Alzheimer's disease. An understanding of the contribution of these variants to the development of Alzheimer's disease has several clinical implications, including enhancing diagnostic accuracy and providing targets for the development of novel treatments. PMID:27302364

  9. Regulatory T cells delay disease progression in Alzheimer-like pathology.

    Science.gov (United States)

    Dansokho, Cira; Ait Ahmed, Dylla; Aid, Saba; Toly-Ndour, Cécile; Chaigneau, Thomas; Calle, Vanessa; Cagnard, Nicolas; Holzenberger, Martin; Piaggio, Eliane; Aucouturier, Pierre; Dorothée, Guillaume

    2016-04-01

    Recent studies highlight the implication of innate and adaptive immunity in the pathophysiology of Alzheimer's disease, and foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results in mouse models, but severe side effects attributed to T cell responses in the first clinical trial AN1792 underlined the need for better understanding adaptive immunity in Alzheimer's disease. We previously showed that regulatory T cells critically control amyloid-β-specific CD4(+)T cell responses in both physiological and pathological settings. Here, we analysed the impact of regulatory T cells on spontaneous disease progression in a murine model of Alzheimer's disease. Early transient depletion of regulatory T cells accelerated the onset of cognitive deficits in APPPS1 mice, without altering amyloid-β deposition. Earlier cognitive impairment correlated with reduced recruitment of microglia towards amyloid deposits and altered disease-related gene expression profile. Conversely, amplification of regulatory T cells through peripheral low-dose IL-2 treatment increased numbers of plaque-associated microglia, and restored cognitive functions in APPPS1 mice. These data suggest that regulatory T cells play a beneficial role in the pathophysiology of Alzheimer's disease, by slowing disease progression and modulating microglial response to amyloid-β deposition. Our study highlights the therapeutic potential of repurposed IL-2 for innovative immunotherapy based on modulation of regulatory T cells in Alzheimer's disease. PMID:26912648

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

    Science.gov (United States)

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

    2006-06-01

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

  11. Copper Chelation in Alzheimer's Disease Protein

    Science.gov (United States)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2013-03-01

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

  12. Neuroimaging in the diagnosis of Alzheimer's disease

    International Nuclear Information System (INIS)

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

  13. Alzheimer disease pathology as a host response.

    Science.gov (United States)

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

    2008-06-01

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

  14. Auditory confrontation naming in Alzheimer's disease.

    Science.gov (United States)

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

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Kedar N

    2003-01-01

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

  16. The age factor in Alzheimer's disease.

    Science.gov (United States)

    Guerreiro, Rita; Bras, Jose

    2015-01-01

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

  17. Statistical parametric mapping in the detection of rCBF changes in mild Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, C.; Barnden, L.; Boundy, K.; McKinnon, J.; Liptak, M. [The Queen Elizabeth Hospital, Adelaide, SA (Australia). Departments of Nuclear Medicine and Neurology

    1998-06-01

    Full text: Reduction in temporoparietal regional cerebral blood flow (rCBF) is proportional to the degree of cognitive deficit in patients with Alzheimer`s Disease (AD). The characteristic pattern is readily apparent in advanced disease but is often subtle in early stage AD, reducing the clinical value of SPECT in the management of this condition. We have previously reported that Statistical Parametric Mapping (SPM95) revealed significant temporoparietal hypoperfusion when 10 patients with mild AD (classified by the Clinical Dementia Rating Scale) were compared to 10 age matched normals. We have now begun to evaluate the sensitivity and specificity of SPM95 in individuals with mild AD by comparison to our bank of 39 normals (30 female, 9 male, age range 26 to 74, mean age 52). Preliminary results reveal low sensitivity (<40%) when the standard reference region for normalization (i.e. global brain counts) is used. Better results are expected from normalizing to the cerebellum or basal ganglia and this is under investigation. An objective method to improve the accuracy of rCBF imaging for the diagnosis of early AD would be very useful in clinical practice. This study will demonstrate whether SPM can fulfill this role

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

    Directory of Open Access Journals (Sweden)

    Enrico Mossello

    2011-01-01

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

  19. Fast and robust extraction of hippocampus from MR images for diagnostics of Alzheimer's disease

    DEFF Research Database (Denmark)

    Lötjönen, Jyrki; Wolz, Robin; Koikkalainen, Juha;

    2011-01-01

    Assessment of temporal lobe atrophy from magnetic resonance images is a part of clinical guidelines for the diagnosis of prodromal Alzheimer's disease. As hippocampus is known to be among the first areas affected by the disease, fast and robust definition of hippocampus volume would be of great...... method is about 2 minutes on a standard laptop computer. The results show a clear potential for applying the method in clinical practice....

  20. Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment

    OpenAIRE

    Balañá Montse; Gobartt Ana L; Fernández Manuel

    2010-01-01

    Abstract Background Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated to Alzheimer's disease (AD). The characterization of the clinical profile of AD patients might help to better understand disease evolution and to improve diagnosis and treatment. Thus, the aim of the present study is to describe the clinical profile of AD patients, and to correlate the presence of BPSD with the severity of the disease. Methods A cross-sectional, observa...

  1. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

    OpenAIRE

    Gross Hyman; Tobinick Edward L

    2008-01-01

    Abstract Background Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the b...

  2. A prospective study of nutrition education and oral nutritional supplementation in patients with Alzheimer's disease

    OpenAIRE

    Brant César Q; Okamoto Ivan H.; Novo Neil F.; Juliano Yara; da Silva Rosimeire V; Pivi Glaucia AK; Bertolucci Paulo HF

    2011-01-01

    Abstract Background Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance. Objectives To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD. Methods A randomized, prospective 6-month study which enrolled 90 subjects with probable AD aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27], Education Group (EG) [n = 25...

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

    Science.gov (United States)

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

  4. Neuroprotective peptides related to Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

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

    2004-01-01

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

  5. B Vitamins Fail to Prevent Alzheimer's

    Science.gov (United States)

    ... ARTICLES CLICK HERE B Vitamins Fail to Prevent Alzheimer’s Many people take B vitamins in the hopes ... Finder See All articles W e can end Alzheimer's Support the pioneering research of Nobel Laureate Dr. ...

  6. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  7. Lithium May Fend off Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 夏红

    2004-01-01

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

  8. 10 Early Signs and Symptoms of Alzheimer's

    Science.gov (United States)

    ... of them, please see a doctor. 1. MEMORY LOSS THAT DISRUPTS DAILY LIFE One of the most common signs of Alzheimer's is memory loss, especially forgetting recently learned information. Others include forgetting ...

  9. Alzheimer's and Dementia Testing for Earlier Diagnosis

    Science.gov (United States)

    ... Alzheimer's. However, scientists have not yet agreed upon standardized values for brain volume that would establish the ... samples. Its ultimate goal is to determine whether standardized imaging protocols, possibly combined with laboratory and psychological ...

  10. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

  11. Alzheimer's Caregivers - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

  12. 2016 Alzheimer's disease facts and figures.

    Science.gov (United States)

    2016-04-01

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

  13. 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.

  14. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

  15. Advances in the study of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Angue Nkoghe Francoise; Yunman Li

    2005-01-01

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

  16. 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

  17. Estrógenos, envejecimiento y enfermedad de Alzheimer Estrogens, aging and Alzheimer's dosiase

    Directory of Open Access Journals (Sweden)

    Fabio Sánchez E.

    1999-03-01

    Full Text Available El posible papel protector que ejercen los estrógenos en el envejecimiento y en la prevención de la enfermedad de Alzheimer es un tema de mucho interés y de investigación hoy en día. Existen evidencias de que la merma en la producción de estrógenos después de la menopausia está asociada con deterioro cognitivo que puede subsanarse o prevenirse con el uso de terapia de sustitución hormonal. Algunos estudios han concluido, además, que la terapia de sustitución hormonal con estrógenos se relaciona con disminución del riesgo de desarrollar enfermedad de Alzheimer o, por lo menos, con un retardo en su inicio. Otros estudios clínicos evidencian, aunque de manera preliminar, que los estrógenos pueden mejorar las funciones cognitivas en mujeres con enfermedad de Alzheimer. Sin embargo, estas evidencias no son suficientes aún para recomendar el uso indiscriminado de estrógenos en todas las mujeres postmenopáusicas ni en las afectadas por demencia. Habrá que esperar los resultados del estudio prospectivo WHI-MS que analizará los efectos de la terapia de sustitución hormonal sobre el desarrollo de la demencia en una gran población femenina. Este estudio los definirá a más tardar en unos 7 años. Ante una enfermedad incurable como la de Alzheimer, cualquier terapia que ofrezca un retardo en la edad de aparición, que reduzca su severidad o la velocidad de progresión o produzca mejoría en la calidad de vida, se convierte de hecho en asunto de interés para todos los afectados y para la comunidad científica que estudia este trastorno. The possible protective role of estrogens in aging and Alzheimer‘s disease, is presently a subject of considerable interest and research. There are evidences that decreased estrogen production after menopause is associated with cognitive deterioration that can be prevented or corrected with hormonal substitution therapy (HST. Some studies have concluded that HST with estrogens is related with a

  18. Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways

    Science.gov (United States)

    Hof, P. R.; Vogt, B. A.; Bouras, C.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    In recent years, the existence of visual variants of Alzheimer's disease characterized by atypical clinical presentation at onset has been increasingly recognized. In many of these cases post-mortem neuropathological assessment revealed that correlations could be established between clinical symptoms and the distribution of neurodegenerative lesions. We have analyzed a series of Alzheimer's disease patients presenting with prominent visual symptomatology as a cardinal sign of the disease. In these cases, a shift in the distribution of pathological lesions was observed such that the primary visual areas and certain visual association areas within the occipito-parieto-temporal junction and posterior cingulate cortex had very high densities of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in Alzheimer's disease. Previous quantitative analyses have demonstrated that in Alzheimer's disease, primary sensory and motor cortical areas are less damaged than the multimodal association areas of the frontal and temporal lobes, as indicated by the laminar and regional distribution patterns of neurofibrillary tangles and senile plaques. The distribution of pathological lesions in the cerebral cortex of Alzheimer's disease cases with visual symptomatology revealed that specific visual association pathways were disrupted, whereas these particular connections are likely to be affected to a less severe degree in the more common form of Alzheimer's disease. These data suggest that in some cases with visual variants of Alzheimer's disease, the neurological symptomatology may be related to the loss of certain components of the cortical visual pathways, as reflected by the particular distribution of the neuropathological markers of the disease.

  19. Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    François-B. Vialatte

    2011-01-01

    Full Text Available Objective. EEG has great potential as a cost-effective screening tool for Alzheimer's disease (AD. However, the specificity of EEG is not yet sufficient to be used in clinical practice. In an earlier study, we presented preliminary results suggesting improved specificity of EEG to early stages of Alzheimer's disease. The key to this improvement is a new method for extracting sparse oscillatory events from EEG signals in the time-frequency domain. Here we provide a more detailed analysis, demonstrating improved EEG specificity for clinical screening of MCI (mild cognitive impairment patients. Methods. EEG data was recorded of MCI patients and age-matched control subjects, in rest condition with eyes closed. EEG frequency bands of interest were θ (3.5–7.5 Hz, α1 (7.5–9.5 Hz, α2 (9.5–12.5 Hz, and β (12.5–25 Hz. The EEG signals were transformed in the time-frequency domain using complex Morlet wavelets; the resulting time-frequency maps are represented by sparse bump models. Results. Enhanced EEG power in the θ range is more easily detected through sparse bump modeling; this phenomenon explains the improved EEG specificity obtained in our previous studies. Conclusions. Sparse bump modeling yields informative features in EEG signal. These features increase the specificity of EEG for diagnosing AD.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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.

  2. Frontal variant of Alzheimer's disease and typical Alzheimer's disease: a comparative study

    Directory of Open Access Journals (Sweden)

    Bernardino Fernández-Calvo

    2013-01-01

    Full Text Available Clinical heterogeneity is one of the characteristics of Alzheimer's disease (AD. Hence, the atypical frontal or dysexecutive presentation is becoming increasingly well-known, although the underlying factors are still unknown. In this study, the neuropsychological performance of two groups of patients with AD (frontal variant--ADfv--and typical--TAD were compared. The ADfv group (n = 13 was selected due to the existence of frontal hypoperfusion on a simple photon emission computer tomography (SPECT. The results revealed that the ADfv group displayed a severe dysexecutive disorder, more severe neuropsychiatric symptomatology (disinhibition and apathy, more functional impairment, and it generated a higher caregiver overload than the TAD group without frontal impairment (n = 47. Despite the facts that the ADfv group's performance was poorer in all the neuropsychological tests, significant group differences were only found in the processing speed and visuoconstruction tasks. Logistic regression analysis revealed that the processing speed and mental flexibility scores significantly predicted a diagnosis of ADfv. The existence of the grasp reflex, anosognosia, and the absence of apolipoprotein E epsilon 4 allele (APOE e4 were also more prevalent in the ADfv group. This group had a predominance of males and it was more likely to have a positive family history of AD. To conclude, the study suggests that ADfv represents a subtype of AD that seems to have different clinical, neuropsychological, and genetic characteristics from TAD.

  3. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-02-01

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

  5. Study plan for dementia patients and differential diagnosis with Alzheimer's disease Plan de estudio del paciente con demencia y diagnóstico diferencial con el Alzheimer

    OpenAIRE

    Francisco Lopera Restrepo

    1997-01-01

    Dementia is a disorder with multiple etiologies. A diagnostic plan must be established before starting the study of a dementia patient, including clinical history, and physical and neurological exams. Key data should be searched through the history on the development of the disease and the familiar background of dementia. Even though Alzheimer's dementia (AD) is the most frequent one, the diagnosis of this disorder should only be established when other causes have been ruled out. This paper p...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-02-01

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

  7. Genetic variants in Alzheimer disease - molecular and brain network approaches.

    Science.gov (United States)

    Gaiteri, Chris; Mostafavi, Sara; Honey, Christopher J; De Jager, Philip L; Bennett, David A

    2016-07-01

    Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID:27282653

  8. Ultra-trace graphene oxide in a water environment triggers Parkinson's disease-like symptoms and metabolic disturbance in zebrafish larvae.

    Science.gov (United States)

    Ren, Chaoxiu; Hu, Xiangang; Li, Xueyan; Zhou, Qixing

    2016-07-01

    Over the past decade, the safety of nanomaterials has attracted attention due to their rapid development. The relevant health threat of these materials remains largely unknown, particularly at environmentally or biologically relevant ultra-trace concentrations. To address this, we first found that graphene oxide (GO, a carbon nanomaterial that receives extensive attention across various disciplines) at concentrations of 0.01 μg/L-1 μg/L induced Parkinson's disease-like symptoms in zebrafish larvae. In this model, zebrafish showed a loss of more than 90% of dopamine neurons, a 69-522% increase in Lewy bodies (α-synuclein and ubiquitin) and significantly disturbed locomotive activity. Moreover, it was also shown that GO was able to translocate from the water environment to the brain and localize to the nucleus of the diencephalon, thereby inducing structural and morphological damage in the mitochondria. Cell apoptosis and senescence were triggered via oxidative stress, as shown by the upregulation of caspase 8 and β-galactosidase. Using metabolomics, we found that the upregulation of amino acid and some fatty acids (e.g. dodecanoic acid, hexadecanoic acid, octadecenoic acid, nonanoic acid, arachidonic acid, eicosanoic acid, propanoic acid and benzenedicarboxylic acid) metabolism and the downregulation of some other fatty acids (e.g. butanoic acid, phthalic acid and docosenoic acid) are linked to these Parkinson's disease-like symptoms. These findings broaden our understanding of nanomaterial safety at ultra-trace concentrations. PMID:27085073

  9. ANÁLISIS DEL DESEMPEÑO DEL LENGUAJE EN SUJETOS CON DEMENCIA TIPO ALZHEIMER (DTA Analysis of the language performance in subjects with Alzheimer type dementia (ATD

    Directory of Open Access Journals (Sweden)

    Catalina Malagón M

    2005-01-01

    Full Text Available Antecedentes: la demencia tipo Alzheimer representa un 50-70% de las enfermedades demenciales. Su prevalencia es del 3-5% en personas mayores de 65 años y su incidencia de 1-2% al año en la población general; se caracteriza por alteraciones progresivas en la memoria, el lenguaje, la atención, el comportamiento y la presencia de déficit visoespaciales. Objetivo: hacer un análisis descriptivo-comparativo de una muestra poblacional con demencia tipo Alzheimer, en especial una descripción fenomenológica de las alteraciones del lenguaje presentes en esa población. Métodos: como criterios de inclusión se usaron: diagnóstico de demencia tipo Alzheimer, dominancia manual derecha, escolaridad superior a quinto de primaria y capacidad para rendir las pruebas propuestas. Se comparó el rendimiento en las subpruebas de lenguaje del examen mínimo del estado mental (MMSE; en denominación y fluidez semántica y fonológica y se analizó el deterioro lingüístico en dos estadios de la demencia tipo Alzheimer. Resultados: en el estadio leve se evidencian déficit ligeros en todas las pruebas. Sin embargo los dominios con rendimiento más bajo fueron la fluidez fonológica y semántica. En el estadio moderado se evidenciaron diferencias en el rendimiento;las tareas de denominación, fluidez semántica y fluidez fonológica tuvieron rendimiento más bajo. Conclusiones: el lenguaje es un dominio que suele comprometerse en la demencia tipo Alzheimer. Los resultados reflejan el deterioro progresivo de la habilidad lingüística, manifiesto en un amplio rango de frecuencia entre el estadio leve y el moderado de la demencia. Existe un perfil similar de deterioro para los estadios leve y moderado con patrones independientes en las pruebas específicas.Background: Alzheimer disease explains near 70% of all instances of dementia and its prevalence in 65 years old population is 3-5% while incidence is near 1-2 % per year in general population. The clinical

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  12. Alzheimer's Disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

  13. Dietary intake of antioxidants and risk of Alzheimer disease

    NARCIS (Netherlands)

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

    2002-01-01

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

  14. Simple Steps Can Ease Care of Loved One with Alzheimer's

    Science.gov (United States)

    ... Steps Can Ease Care of Loved One With Alzheimer's Limit their choices and distractions and always keep ... 2016 FRIDAY, March 25, 2016 (HealthDay News) -- As Alzheimer's disease progresses, patients find that simple tasks become ...

  15. Alzheimer's Can Steal Ability to Know Loved Ones' Faces

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158296.html Alzheimer's Can Steal Ability to Know Loved Ones' Faces ... often called one of the cruelest effects of Alzheimer's disease -- the patient's inability to recognize loved ones. ...

  16. Caregivers Often Give Up Necessities to Cover Alzheimer's Costs

    Science.gov (United States)

    ... html Caregivers Often Give Up Necessities to Cover Alzheimer's Costs Many skip food and health care, cut ... 30, 2016 (HealthDay News) -- Caring for someone with Alzheimer's disease means caregivers often skimp on their own ...

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

    Medline Plus

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

  18. Are People with Rosacea At Higher Risk for Alzheimer'S?

    Science.gov (United States)

    ... Are People With Rosacea at Higher Risk for Alzheimer's? Danish study finds a correlation, but patients shouldn' ... linked to a higher risk for dementia and Alzheimer's disease, new research suggests. However, the study authors ...

  19. HIV Patients Now Living Long Enough to Develop Alzheimer's

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158394.html HIV Patients Now Living Long Enough to Develop Alzheimer's ... of Alzheimer's disease diagnosed in a person with HIV highlights the fact that long-time HIV survivors ...

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

    Medline Plus

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

  1. Behavior Changes May Be First Signs of Alzheimer's

    Science.gov (United States)

    ... html Behavior Changes May Be First Signs of Alzheimer's Researchers have developed a checklist to help spot ... Certain behavior changes may be a harbinger of Alzheimer's disease, and researchers say they've developed a ...

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

    Medline Plus

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

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

    Medline Plus

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

  4. HIV Patients Now Living Long Enough to Develop Alzheimer's

    Science.gov (United States)

    ... HIV Patients Now Living Long Enough to Develop Alzheimer's Findings upend previous beliefs about brain changes related ... 19, 2016 (HealthDay News) -- The first case of Alzheimer's disease diagnosed in a person with HIV highlights ...

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

    Medline Plus

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

  6. Loss of Y Chromosome in Men Tied to Alzheimer's Risk

    Science.gov (United States)

    ... Loss of Y Chromosome in Men Tied to Alzheimer's Risk Study raises provocative questions, expert says To ... age may have an increased risk of developing Alzheimer's disease, a new study suggests. The study of ...

  7. Why Pleasant Mealtimes Could Be Key to Alzheimer's Care

    Science.gov (United States)

    ... html Why Pleasant Mealtimes Could Be Key to Alzheimer's Care Enhanced atmosphere reduces odds of malnutrition, dehydration, ... Services, or federal policy. More Health News on: Alzheimer's Disease Dementia Nutrition for Seniors Recent Health News ...

  8. People-Oriented Jobs May Help Lower Alzheimer's Risk

    Science.gov (United States)

    ... 160050.html People-Oriented Jobs May Help Lower Alzheimer's Risk Activities that highly stimulate the brain might ... the effects of brain lesions commonly associated with Alzheimer's disease, report researchers from the University of Wisconsin's ...

  9. Healthy Diet, Exercise May Help Keep Alzheimer's At Bay

    Science.gov (United States)

    ... 160477.html Healthy Diet, Exercise May Help Keep Alzheimer's at Bay Study finds people who are active ... your brain free of changes that lead to Alzheimer's disease, a small study suggests. Researchers studied 44 ...

  10. Even Gardening or Dancing Might Cut Alzheimer's Risk

    Science.gov (United States)

    ... 157731.html Even Gardening or Dancing Might Cut Alzheimer's Risk Any regular physical activity is linked to ... physical activity, including gardening or dancing, may cut Alzheimer's risk by as much as 50 percent, a ...

  11. Women with Alzheimer's May Keep Verbal Skills Longer Than Men

    Science.gov (United States)

    ... gov/medlineplus/news/fullstory_157801.html Women With Alzheimer's May Keep Verbal Skills Longer Than Men Gender ... 2016 (HealthDay News) -- In the early stages of Alzheimer's disease, women tend to remember words better than ...

  12. Desintegración de las praxias en la enfermedad de Alzheimer Disintegration of praxias in Alzheimer's disease: a case report

    Directory of Open Access Journals (Sweden)

    Carlos A. Bardeci

    1972-03-01

    Full Text Available Se describe la sintomatologia clínica, los resultados de métodos auxiliares y de la punción biopsia cerebral de una paciente con enfermedad de Alzheimer. Se analizan los diversos aspectos clínicos, sosteniendose como posible determinar la individualidad clínica de la enfermedad de Alzheimer, dentro del capítulo de las demencias preseniles y su diagnóstico en vida. Las formas de apraxia presentes en esta observación confirman la correlación estrecha que existe entre los distintos niveles de su desintegración, à su relación con las perturbaciones del espacio al cual están genéticamente vinculadas; el espacio euclidiano para la apraxia constructiva, el espacio centrado en el propio cuerpo para la ideomotora y el concreto de manipulación de objetos para la ideatoria.The case of a patient with Alzheimer's disease is reported and some considerations about the clinical individuality of the disease and the characteristics shown by the disintegration of behavior are made. In the study, the following methods were used: neurological examinations focused especially on movement disturbances, ecoencephalography, electroencephalography, cerebral cintilography, right carotid arteriography and cerebral biopsy. The clinical aspects of the disease, just as the correlation of the data obtained by the auxiliary methods allow the formulation of the diagnosis, confirmed by right frontal cerebral puncture. The patient's clinical context shows the basic syndromes: 1 frontal with fixative amnesia, lack of interest, deterioration of the consciousness of situation and of the intellectual level, bilateral apprehension reflex; 2 parieto-temporo-occipital with indifference for the left hemibody, for the visual hemifield and for the space of this side. In addition, there arises a serious complication of motor behavior (praxias with the disintegration of all functional levels: instrumental (melokinesic apraxia, space linked to the body (ideomotor, Euclidean space

  13. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Gross Hyman

    2008-07-01

    Full Text Available Abstract Background Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the brain. We hypothesized that perispinal etanercept had the potential to improve verbal function in Alzheimer's disease, so we included several standarized measures of verbal ability to evaluate language skills in a clinical trial of perispinal etanercept for Alzheimer's disease. Methods This was a prospective, single-center, open-label, pilot study, in which 12 patients with mild-to-severe Alzheimer's disease were administered etanercept, 25–50 mg, weekly by perispinal administration for six months. Two additional case studies are presented. Results Two-tailed, paired t-tests were conducted comparing baseline performance to 6-month performance on all neuropsychological measures. Test batteries included the California Verbal Learning Test-Second Edition, Adult Version; Logical Memory I and II(WMS-LM-II from the Wechsler Memory Scale-Abbreviated; the Comprehensive Trail Making Test (TMT; Boston Naming Test; and letter(FAS and category verbal fluency. All measures revealed a significant effect except for the Boston Naming Test and the TMT-4, with WMS-LM-II being marginally significant at p = .05. The FAS test for letter fluency was most highly significant with a p Conclusion In combination with the previously reported results of perispinal etanercept in Alzheimer's disease and primary progressive aphasia, these results further argue that larger scale studies of this therapeutic intervention, including Phase 3 trials, are warranted in dementias. In addition

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

    Science.gov (United States)

    Leuzy, Antoine; Gauthier, Serge

    2012-05-01

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

  15. New compounds as potential radio diagnosticians Alzheimer

    International Nuclear Information System (INIS)

    Alzheimer's disease (AD) is the most common cause of dementia in Cuba and all over the World. According to demographic trends it has been called the epidemic of the century. It is characterized by the presence of neuropathological brain deposits: senile plaques, formed by neurofibrillary tangles (NT) and deposits of β-amyloid protein (Aß). Aß plaques could appear even 20 years before the establishment of first clinical symptoms of the disease. The aim of this study was to synthesize new naphthalene derivatives, feasible to be labeled with radionuclides emitters of either gamma radiation or positrons. These labeled compounds should be able to cross blood–brain barrier (BBB) in healthy and AD transgenic animals. As a result of this work, several synthetic precursors were synthesized, which were labeled with iodine-131, carbon-11 and fluorine-18 with a satisfactory radiochemical purity. The corresponding non-radioactive control compounds were also synthesized.In in vitro and in silico studies, obtained compounds showed affinity for the β-amyloid protein. According to SPECT and PET-CT images in healthy laboratory animals, obtained labeled compounds crossed BBB in a bi-directional way without any sign of brain uptake.Furthermore, evaluation of the biodistribution of the [18F] -2- (3-fluoropropyl) -6-methoxynaphthalene ([[18F] Amyloid® was performed in healthy animals.[[18F]Amylovis crossed blood brain barrier. Renal and hepatic pathways were the main excretion routes. On the other hand, in transgenic mice with AD, its uptake and its retention time were higher in comparison with healthy mice. Immunohistochemistry and Congo red staining of control and transgenic mice brain slices were performed to identify β-amyloid plaques.Conclusions: Obtained compounds were able to bi-directionally cross BBB.[[18F]Amylovis® could be a promising PET radiotracer for amyloid plaques visualization. (author)

  16. Homonymous Hemianopsia Associated with Probable Alzheimer's Disease.

    Science.gov (United States)

    Ishiwata, Akiko; Kimura, Kazumi

    2016-01-01

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

  17. Geriatric Dentistry and the Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Marcelo Coelho GOIATO

    2006-08-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  19. Raman spectroscopy of Alzheimer's diseased tissue

    Science.gov (United States)

    Sudworth, Caroline D.; Krasner, Neville

    2004-07-01

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

  20. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

    Directory of Open Access Journals (Sweden)

    Adriana Cristofano

    Full Text Available This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L to subjective memory complaint (4.3±0.9 μmol/L, mild cognitive impairment (4.0±0.53 μmol/L, up to Alzheimer's disease (3.5±0.6 μmol/L group (p<0.001. The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  1. Nuclear microscopy in Alzheimer's disease

    International Nuclear Information System (INIS)

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

  2. Quantitative evaluation of Alzheimer's disease

    Science.gov (United States)

    Duchesne, S.; Frisoni, G. B.

    2009-02-01

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

  3. Metal exposure and Alzheimer's pathogenesis.

    Science.gov (United States)

    Liu, Guijian; Huang, Weidong; Moir, Robert D; Vanderburg, Charles R; Lai, Barry; Peng, Zicheng; Tanzi, Rudolph E; Rogers, Jack T; Huang, Xudong

    2006-07-01

    With the growing aging population in Western countries, Alzheimer's disease (AD) has become a major public health concern. No preventive measure and effective treatment for this burdensome disease is currently available. Genetic, biochemical, and neuropathological data strongly suggest that Abeta amyloidosis, which originates from the amyloidogenic processing of a metalloprotein-amyloid precursor protein (APP), is the key event in AD pathology. However, neurochemical factors that impact upon the age-dependent cerebral Abeta amyloidogenesis are not well recognized. Growing data indicate that cerebral dysregulation of biometals, environmental metal exposure, and oxidative stress contribute to AD pathology. Herein we provided further evidence that both metals (such as Cu) and H(2)O(2) promote formation of neurotoxic Abeta oligomers. Moreover, we first demonstrated that laser capture microdissection coupled with X-ray fluorescence microscopy can be applied to determine elemental profiles (S, Fe, Cu, and Zn) in Abeta amyloid plaques. Clearly the fundamental biochemical mechanisms linking brain biometal metabolism, environmental metal exposure, and AD pathophysiology warrant further investigation. Nevertheless, the study of APP and Abeta metallobiology may identify potential targets for therapeutic intervention and/or provide diagnostic methods for AD. PMID:16503166

  4. An anemia of Alzheimer's disease.

    Science.gov (United States)

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

    2014-11-01

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

  5. Functional neuroimaging in Alzheimer's disease

    International Nuclear Information System (INIS)

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

  6. Dyslipidemia and Blood-Brain Barrier Integrity in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Gene L. Bowman

    2012-01-01

    Full Text Available Background. Blood-brain barrier (BBB dysfunction may have a significant role in the pathogenesis of Alzheimer's disease (AD. Modifiable factors associated with BBB function may have therapeutic implication. This study tested the hypothesis that dyslipidemia is associated with BBB impairment in mild-to-moderate AD. Methods. Thirty-six subjects with AD were followed for 1 year. Fasting CSF and plasma were collected with clinical assessments at baseline and 12 months. BBB impairment was defined as CSF albumin index ≥9. Independent t-tests and linear regression assessed the relationship between plasma lipoproteins and BBB integrity. Results. Dyslipidemia was prevalent in 47% of the population, and in 75% of those with BBB impairment. Subjects with BBB impairment had significantly higher mean plasma triglyceride and lower HDL cholesterol (TG, P=0.007; HDL, P=0.043. Plasma triglycerides explained 22% of the variance in BBB integrity and remained significant after controlling for age, gender, ApoE-4 genotype, blood pressure, and statin use. Conclusion. Dyslipidemia is more prevalent in AD subjects with BBB impairment. Plasma triglyceride and HDL cholesterol may have a role in maintaining BBB integrity in mild-to-moderate Alzheimer's disease.

  7. Alzheimer's disease: is a vaccine possible?

    International Nuclear Information System (INIS)

    The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility

  8. Alzheimer's disease: is a vaccine possible?

    Energy Technology Data Exchange (ETDEWEB)

    Alves, R.P.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil); Yang, M.J. [Instituto Butantan, Laboratório de Genética, São Paulo, SP, Brasil, Laboratório de Genética, Instituto Butantan, São Paulo, SP (Brazil); Batista, M.T.; Ferreira, L.C.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-05-09

    The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

  9. A comparative study of Alzheimer's disease and Pick's disease by CT

    International Nuclear Information System (INIS)

    17 patients with clinically diagnosed Alzheimer's disease, 11 patients with clinically diagnosed Pick's disease and 13 healthy age-matched subjects as the control were studied by computed tomography (CT). In order to study cerebral atrophy, volumetric measurement was performed. Subarachnoid Space Volume Index (SVI). Frontal, Temporal, and Parieto-Occipital Subarachnoid Space Volume Indices (SfVI, StVI, and SpoVI, respectively) as well as Ventricle Volume Index (VVI), The volume indices of anterior horn, inferior horn, and posterior horn of the lateral ventricles (VaVI, ViVI, and VpVI, respectively) were calculated as the indices for the atrophy of the cerebral cortex and white matter. Furthermore, to evaluate lobar atrophy, SfVI+VaVI (FA), StVI+ViVI (TA), and SpoVI+VpVI (POA) were defined as the indices of frontal lobe atrophy, temporal lobe atrophy, and parieto-occipital lobe atrophy respectively. In Alzheimer's patients, FA and POA were significantly large (p<0.001) in stage I group and TA was significantly enlarged (p<0.001) in stage II group. In Pick's patients, FA and TA were significantly large (FA : p<0.001, TA : p<0.01) in stage I group and POA became significantly prominent (p<0.001) in stage III group. Pick's patients showed significantly larger SfVI (p<0.2 in stage I group and p<0.001 in stage II group) and FA (p<0.01 in stage II group) than Alzheimer's patients. The results in this study give us the following suggestions; 1) Alzheimer's patients show a diffuse cerebral atrophy in the early stage. 2) Pick's patients have a localized atrophy of frontal and temporal lobes already in the early stage. 3) Compared with Alzheimer's patients, Pick's patients show significantly more severe atrophy in frontal lobe at the early stage. (J.P.N.)

  10. Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer's Disease.

    Science.gov (United States)

    Saavedra, Juan M

    2016-03-01

    Alzheimer's disease is the most frequent type of dementia and diagnosed late in the progression of the illness when irreversible brain tissue loss has already occurred. For this reason, treatments have been ineffective. It is imperative to find novel therapies ameliorating modifiable risk factors (hypertension, stroke, diabetes, chronic kidney disease, and traumatic brain injury) and effective against early pathogenic mechanisms including alterations in cerebral blood flow leading to poor oxygenation and decreased access to nutrients, impaired glucose metabolism, chronic inflammation, and glutamate excitotoxicity. Angiotensin II receptor blockers (ARBs) fulfill these requirements. ARBs are directly neuroprotective against early injury factors in neuronal, astrocyte, microglia, and cerebrovascular endothelial cell cultures. ARBs protect cerebral blood flow and reduce injury to the blood brain barrier and neurological and cognitive loss in animal models of brain ischemia, traumatic brain injury, and Alzheimer's disease. These compounds are clinically effective against major risk factors for Alzheimer's disease: hypertension, stroke, chronic kidney disease, diabetes and metabolic syndrome, and ameliorate age-dependent cognitive loss. Controlled studies on hypertensive patients, open trials, case reports, and database meta-analysis indicate significant therapeutic effects of ARBs in Alzheimer's disease. ARBs are safe compounds, widely used to treat cardiovascular and metabolic disorders in humans, and although they reduce hypertension, they do not affect blood pressure in normotensive individuals. Overall, there is sufficient evidence to consider long-term controlled clinical studies with ARBs in patients suffering from established risk factors, in patients with early cognitive loss, or in normal individuals when reliable biomarkers of Alzheimer's disease risk are identified. PMID:26993513

  11. La alimentación del enfermo de Alzheimer en el ámbito familiar Alzheimer`s disease patients nutrition in the domestic environment

    Directory of Open Access Journals (Sweden)

    J. J. Botella Trelis

    2004-05-01

    Full Text Available La enfermedad de Alzheimer afecta a un gran número de enfermos que viven en su entorno familiar, conocer su situación, cuáles son sus hábitos dietéticos y cómo afrontan la edad, es importante para mejorar su calidad de vida. Pacientes y método: Enfermos de la Asociación de Alzheimer de Valencia que viven en el domicilio familiar. Los parámetros estudiados fueron: sexo, evolución de la demencia, tiempo transcurrido desde el diagnóstico, peso, hábitos dietéticos y frecuencia de consumo de alimentos, disfagia, aparición de complicaciones e información recibida por los cuidadores. Resultados: 241 enfermos, 70% mujeres, edad media de 76 años, 52% diagnosticados entre 3 y 6 años, 48% con demencia severa (GDS ≥ 6. Se encontró pérdida de peso en el 31%. Ingesta por vía oral en el 98%. Seguían una dieta equilibrada el 24%. Ingesta de líquidos superor a 4 vasos el 28%. El 91% preparan siempre la comida en el domicilio, triturados el 40%, disfagia a líquidos 26% y a sólidos 19%. El 5% de los cuidadores está totalmente desinformado sobre la enfermedad y la mitad no ha recibio información sobre alimentación. Conclusión: La alimentación se realiza prácticamente en su totalidad por vía oral, se sigue una dieta bastante equilibrada, a pesar de la evolución de la demencia y de la aparición de disfagia. La ingesta de líquidos es, insuficiente y bastantes enfermos pierden peso, otras complicaciones son escasas. Hay un gran desconocimiento en cuanto a la alimentación de estos enfermos y a la medidas básicas de adaptación en la evolución de la enfermedad.Most of the patients diagnosed of Alzheimer's disease are still living at home with their relatives. It is important to know their clinical state, nutritional habits and attitudes toward their illness in order to improve their quality of life. Patients and methods: Patients who are members of the Valencia Association of Alzheimer's Disease Realtives, who live with their

  12. Neurodegeneration and Alzheimer's disease (AD). What Can Proteomics Tell Us About the Alzheimer's Brain?

    Science.gov (United States)

    Moya-Alvarado, Guillermo; Gershoni-Emek, Noga; Perlson, Eran; Bronfman, Francisca C

    2016-02-01

    Neurodegenerative diseases, such as Alzheimer's diseases (AD), are becoming more prevalent as the population ages. However, the mechanisms that lead to synapse destabilization and neuron death remain elusive. The advent of proteomics has allowed for high-throughput screening methods to search for biomarkers that could lead to early diagnosis and treatment and to identify alterations in the cellular proteome that could provide insight into disease etiology and possible treatment avenues. In this review, we have concentrated mainly on the findings that are related to how and whether proteomics studies have contributed to two aspects of AD research, the development of biomarkers for clinical diagnostics, and the recognition of proteins that can help elucidate the pathways leading to AD brain pathology. As a result of these studies, several candidate cerebrospinal fluid biomarkers are now available for further validation in different AD cohorts. Studies in AD brain and AD transgenic models support the notion that oxidative damage results in the alterations of metabolic enzymes and that mitochondrial dysfunction is central to AD neuropathology. PMID:26657538

  13. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

    Science.gov (United States)

    Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2015-01-01

    We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. PMID:25189118

  14. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

    Science.gov (United States)

    Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

    2014-04-01

    A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by

  15. Early Detection of Alzheimer's - A Crucial Requirement

    CERN Document Server

    Bukhari, Ijaz

    2013-01-01

    Alzheimer's, an old age disease of people over 65 years causes problems with memory, thinking and behavior. This disease progresses very slow and its identification in early stages is very difficult. The symptoms of Alzheimer's appear slowly and gradually will have worse effects. In its early stages, not only the patients themselves but their loved ones are generally unable to accept that the patient is suffering from disease. In this paper, we have proposed a new algorithm to detect patients of Alzheimer's at early stages by comparing the Magnetic Resonance Images (MRI) of the patients with normal persons of their age. The progress of the disease can also be monitored by periodic comparison of the previous and current MRI.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    Moghul, S; Wilkinson, D

    2001-09-01

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

  18. Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Fellmann Jere

    2006-05-01

    Full Text Available Abstract Background Abnormalities in cerebrospinal fluid (CSF production and turnover, seen in normal pressure hydrocephalus (NPH and in Alzheimer's disease (AD, may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP, consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA criteria for AD, excluding those with signs of concomitant NPH. Methods AD subjects by NINCDS-ADRDA criteria (n = 222, were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO2 of 40 Torr (40 mmHg. Results Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9% enrolled in the study had CSFP of 220 mmH20 or greater, mean 249 ± 20 mmH20 which was significantly higher than 103 ± 47 mmH2O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS. Conclusion Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study.

  19. Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Nielsen, J.E.; Stokholm, J.;

    2008-01-01

    BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic...... features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer...... mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations Udgivelsesdato...

  20. Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors.

    Science.gov (United States)

    Armanini, Decio; Vecchio, Franco; Basso, Alfonso; Milone, Francesco Ferro; Simoncini, Maria; Fiore, Cristina; Mattarello, Mee Joung; Sartorato, Paola; Karbowiak, Isabella

    2003-11-01

    Alzheimer's disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer's disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radio-receptor-assay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer's disease, plasma cortisol was higher than in controls (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21-3.69 vs 3.51, 1.35-9.07 micromol/L; DHEAS/ cortisol: 2.04, range 0.3-5.8 vs 6.8, range 2.7-24 and type II receptors: 1219, 1000-2700 vs 1950, 1035- 2750 receptors per cell; p < 0.001). No correlation was found between the hormonal parameters, age, and mini-mental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's disease, which is probably the consequence of damage to target tissues by corticosteroids. PMID:14665714

  1. A large early-onset Alzheimer`s disease pedigree linked to chromosome 14q24.3

    Energy Technology Data Exchange (ETDEWEB)

    Hannequin, D. [CHU de Rouen (France); Campion, D. [INSERM, U155 Paris (France); Brice, A. [INSERM U289, Paris (France)] [and others

    1994-09-01

    A large French pedigree including 34 subjects with early-onset progressive dementia was identified. In patients, the mean age-at-onset was 46 {plus_minus} 3.5 (SD) years and the mean age at death 52.6 {plus_minus} 5.7 (SD) years. No evidence for anticipation or genetic imprinting was found. Twelve patients were clinically diagnosed as probable Alzheimer`s disease (AD) according to the NINCDS-ADRDA criteria. Myoclonus and extrapyramidal signs were common and seizures were found in all affected subjects. At autopsy, neuropathological changes typical of AD were present in two brains. A significant lod score of 5.38 was observed at a recombination fraction of {theta} = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. Furthermore, no obligate recombinant was observed with markers D14S77 and D14S71. Typing other genetic markers in this region will allow us to localize more precisely the pathological gene.

  2. C9orf72 G(4)C(2) repeat expansions in Alzheimer's disease and mild cognitive impairment

    NARCIS (Netherlands)

    Cacace, Rita; Van Cauwenberghe, Caroline; Bettens, Karolien; Gijselinck, Ilse; van der Zee, Julie; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Van Dongen, Jasper; Baumer, Veerle; Dillen, Lubina; Mattheijssens, Maria; Peeters, Karin; Cruts, Marc; Vandenberghe, Rik; De Deyn, Peter P.; Van Broeckhoven, Christine; Sleegers, Kristel

    2013-01-01

    C9orf72 G(4)C(2) repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Its role in Alzheimer's disease (AD) is less clear. We assessed the prevalence of G(4)C(2) pathogenic repeat expansions in Flanders-Belgian patients with clinical AD or mild cog

  3. Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease

    NARCIS (Netherlands)

    Van der Mussele, Stefan; Bekelaar, Kim; Le Bastard, Nathalie; Vermeiren, Yannick; Saerens, Jos; Somers, Nore; Marien, Peter; Goeman, Johan; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2013-01-01

    Background: Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aims of this study are to determine the prevalence of significant depressive symptoms in MCI and Alzheimer's disease (AD) pati

  4. Positron emission tomography in at risk patients and in the progression of mild cognitive impairment to Alzheimer's disease

    DEFF Research Database (Denmark)

    Rinne, Juha O; Någren, Kjell

    2010-01-01

    Mild cognitive impairment (MCI) is considered a transitional state between the cognitive changes of normal aging and the earliest clinical features of Alzheimer's disease (AD). An important goal is to find features that predict which MCI patients will later convert to AD. Identification of such...

  5. El Alzheimer: Un problema social y sanitario

    OpenAIRE

    Rodríguez Domínguez, Daniel

    2014-01-01

    Actualmente, debido al envejecimiento demográfico y al aumento de la esperanza de vida, cada vez son más las personas mayores que forman parte de nuestra sociedad, lo que también implica un aumento de los casos de enfermedades asociadas a la vejez, como es el caso de la enfermedad de Alzheimer. El Alzheimer, es el tipo de demencia más frecuente que existe entre las personas mayores. Se trata de un trastorno neurodegenerativo irreversible, que provoca el deterioro progresivo de las funci...

  6. Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17

    OpenAIRE

    Kasuga, Kensaku; Kikuchi, Masataka; Tokutake, Takayoshi; Nakaya, Akihiro; Tezuka, Toshiyuki; Tsukie, Tamao; Hara, Norikazu; Miyashita, Akinori; Kuwano, Ryozo; Ikeuchi, Takeshi

    2015-01-01

    Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dem...

  7. Personality and resilience to Alzheimer's disease neuropathology: A prospective autopsy study

    OpenAIRE

    Terracciano, Antonio; Iacono, Diego; O'Brien, Richard J; Troncoso, Juan C.; An, Yang; Sutin, Angelina R.; Ferrucci, Luigi; Zonderman, Alan B.; Resnick, Susan M.

    2012-01-01

    Alzheimer's disease (AD) neuropathology is found at autopsy in about 30% of cognitively normal older individuals. We examine whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. Broad factors and specific facets of personality were assessed up to 28 years (M=11, SD=7) before onset of dementia and up to 30 years (M=15, SD=7) before death in a cohort (N=111) evaluated for AD neuropathology at autopsy. Individuals with higher ...

  8. Probing Alzheimers Disease Pathology and Early Detection at the NSLS with Infrared, XRF, and DEI

    International Nuclear Information System (INIS)

    We explored diffraction enhanced imaging (DEI) in both planar and computed tomography (CT) modes for early detection of beta amyloid deposition, a hallmark feature in Alzheimer's disease (AD). Since amyloid plaques precede clinical symptoms by years, their early detection is of great interest. These findings were correlated with results from synchrotron infrared microspectroscopic imaging and X-ray fluorescence microscopy, to determine the secondary structure of the amyloid beta protein and metal concentration in the amyloid plaques, respectively.

  9. Differences between early and late-onset Alzheimer's disease in neuropsychological tests.

    OpenAIRE

    Francisca eSá; Paula ePinto; Catarina eCunha; Raquel eLemos; Liliana eLetra; Mário eSimões; Isabel eSantana

    2012-01-01

    Although patients with Alzheimer disease (AD) share clinical and histological features regardless of age of onset, the hypothesis that early-onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile. However, investigations are not consensual in terms of cognitive domains affected in each group.Aim: To investigate whether there is early neuropsychological dif...

  10. Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease

    OpenAIRE

    Basi, Guriqbal S; Hemphill, Susanna; Brigham, Elizabeth F.; Liao, Anna; Aubele, Danielle L; Baker, Jeanne; Barbour, Robin; Bova, Michael; Chen, Xiao-Hua; Dappen, Michael S; Eichenbaum, Tovah; Goldbach, Erich; Hawkinson, Jon; Lawler-Herbold, Rose; Hu, Kang

    2010-01-01

    Introduction Inhibition of gamma-secretase presents a direct target for lowering Aβ production in the brain as a therapy for Alzheimer's disease (AD). However, gamma-secretase is known to process multiple substrates in addition to amyloid precursor protein (APP), most notably Notch, which has limited clinical development of inhibitors targeting this enzyme. It has been postulated that APP substrate selective inhibitors of gamma-secretase would be preferable to non-selective inhibitors from a ...

  11. Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy

    OpenAIRE

    Wagshal, D; Sankaranarayanan, S; Guss, V; Hall, T; Berisha, F; Lobach, I; Karydas, A.; Voltarelli, L; Scherling, C; Heuer, H.; Tartaglia, MC; Miller, Z.; G. Coppola; Ahlijanian, M.; SOARES, H

    2014-01-01

    Background Elevated CSF t is considered a biomarker of neuronal injury in newly developed Alzheimer's disease (AD) and mild cognitive impairment (MCI) criteria. However, previous studies have failed to detect alterations of t species in other primary tauopathies. We assessed CSF t protein abnormalities in AD, a tauopathy with prominent Aβ1. Methods 26 normal control (NC), 37 AD, and 24 patients with PSP participated in the study. AD and PSP were matched for severity using the clinical dementi...

  12. Frontotemporal dementia and Alzheimer's disease: retrospective differentiation using information from informants.

    OpenAIRE

    Barber, R; Snowden, J S; Craufurd, D

    1995-01-01

    The study examined the feasibility of differentiating frontotemporal dementia from Alzheimer's disease on the basis of retrospective historical information obtained from relatives of patients. A structured questionnaire was devised of patients' symptoms, with emphasis on those cognitive and neuropsychiatric features found in earlier prospective clinical studies to distinguish the two conditions. The questionnaire was given to close relatives of deceased patients in whom the diagnosis of non-A...

  13. Factors affecting the age of onset and rate of progression of Alzheimer's disease

    OpenAIRE

    Bowler, J.; Munoz, D.; Merskey, H.; HACHINSKI, V.

    1998-01-01

    OBJECTIVES—To assess the role of cerebrovascular disease, sex, education, occupation, year of birth, leukoaraiosis, congophilic angiopathy, family history, and other demographic factors on the reported age of onset and rate of progression of Alzheimer's disease.
METHODS—Analysis of data from the University of Western Ontario Dementia Study, a prospective longitudinal study of dementia patients with clinical and 6 monthly psychometric follow up to postmortem based in a univer...

  14. Molecular imaging in Alzheimer's disease: new perspectives on biomarkers for early diagnosis and drug development

    OpenAIRE

    Nordberg, Agneta

    2011-01-01

    Recent progress in molecular imaging has provided new important knowledge for further understanding the time course of early pathological disease processes in Alzheimer's disease (AD). Positron emission tomography (PET) amyloid beta (Aβ) tracers such as Pittsburgh Compound B detect increasing deposition of fibrillar Aβ in the brain at the prodromal stages of AD, while the levels of fibrillar Aβ appear more stable at high levels in clinical AD. There is a need for PET ligands to visualize smal...

  15. Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

    OpenAIRE

    Shineman, Diana W; Basi, Guriqbal S.; Bizon, Jennifer L.; Colton, Carol A.; Greenberg, Barry D.; Hollister, Beth A; Lincecum, John; Leblanc, Gabrielle G.; Lee, Linda H; Luo, Feng; Morgan, Dave; Morse, Iva; Refolo, Lorenzo M; Riddell, David R; Scearce-Levie, Kimberly

    2011-01-01

    Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical...

  16. A direct comparison of errorless and errorful therapy for object name relearning in Alzheimer's disease.

    OpenAIRE

    Noonan, Krist A.; Pryer, Louise R; Jones, Roy W.; Burns, Alistair S.; Lambon Ralph, Matthew A.

    2012-01-01

    Developing rehabilitation techniques to combat cognitive decline is a key goal of healthcare strategies aimed at promoting increased longevity and better quality of life for individuals with Alzheimer's disease (AD). In AD, problems with episodic memory and word-finding greatly affect everyday life and, as such, these symptoms provide a clear clinical target for therapeutic interventions. Errorless learning (EL) has been proposed as a particularly effective technique for relearning in individ...

  17. Probing Alzheimers Disease Pathology and Early Detection at the NSLS with Infrared, XRF, and DEI

    Energy Technology Data Exchange (ETDEWEB)

    Zhong,Z.; Bennett, D.; Chapman, D.; Chen, J.; Connor, D.; Dilmanian, A.; Faulconer, L.; Kao, T.; Leskovjan, A.; et al

    2008-01-01

    We explored diffraction enhanced imaging (DEI) in both planar and computed tomography (CT) modes for early detection of beta amyloid deposition, a hallmark feature in Alzheimer's disease (AD). Since amyloid plaques precede clinical symptoms by years, their early detection is of great interest. These findings were correlated with results from synchrotron infrared microspectroscopic imaging and X-ray fluorescence microscopy, to determine the secondary structure of the amyloid beta protein and metal concentration in the amyloid plaques, respectively.

  18. Immunotherapy Targeting Pathological Tau Protein in Alzheimer's Disease and Related Tauopathies

    OpenAIRE

    Sigurdsson, Einar M.

    2008-01-01

    Immunotherapies that target the amyloid-β (Aβ) peptide in Alzheimer's disease (AD) have shown promise in animal and human studies. Although the first clinical trial was halted because of adverse reactions, this approach has been refined and additional trials are underway. Another important target in AD is the neurofibrillary tangles, composed primarily of hyperphosphorylated tau proteins, which correlate well with the degree of dementia. As Aβ and tau pathologies are likely synergistic, targe...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-04-24

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-03-01

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