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

  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. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

    Science.gov (United States)

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J.

    2016-01-01

    We examined the brains of 266 patients with prion diseases (PrionD) and found that 46 (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (Hu BrnAggs) to brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease (CJD) and found that the neurons in the Hu BrnAggs produced many β-amyloid (β42) inclusions, whereas uninfected, control-exposed Hu BrnAggs did not. Western blots of 20-pooled CJD-infected BrnAggs verified higher Aβ42 levels than controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many Aβ42 intraneuronal inclusions, low APOE-4, and no significant nerve cell loss. Seven patients had high levels of PrPSc, low Aβ42, high APOE-4 and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls and 2 controls had a few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to AD and suggest that PrionD are diseases of PrPSc, Aβ42, APOE-4 and abnormal tau. PMID:26226132

  4. Focal Cerebral Ischemia Induces Alzheimer s Disease-like Pathological Change in Rats

    Institute of Scientific and Technical Information of China (English)

    王海均; 赵洪洋; 叶佑范; 熊南翔; 黄俊红; 姚东晓; 沈寅; 赵心同

    2010-01-01

    The changes in the tau protein phosphorylation and expression of bcl-2,and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion(I/R)were explored,and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease.The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The le...

  5. Cotinine prevents memory loss and diminishes Alzheimer's disease-like pathology

    Directory of Open Access Journals (Sweden)

    Laura Catalina Charry

    2015-05-01

    Full Text Available Alzheimer's disease (AD affects millions of people around the world and currently there are no effective therapies. Cotinine, a metabolite of nicotine, has been shown to be neuroprotective, prevent memory loss and reduce amyloid-β (Aβ plaque pathology in transgenic AD mice. The beneficial effect that cotinine has on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β. These pro-apoptotic factors promote neuronal survival and the synaptic plasticity processes underlying learning and memory in the hippocampus and cortex of wild type and AD mice. Cotinine has also shown to diminish depressive-like behavior in normal and chronically stressed mice. Additionally, the use of this compound in studies has resulted in an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices. It can be observed in multiple studies, that daily treatment of mice with cotinine reduced Aβ levels and plaque formation compared with vehicle treated mice, which had higher memory loss and depressive behavior. The beneficial effects of cotinine on brain function and good safety profile, suggest that it may be a potential new therapeutic agent against Alzheimer's disease.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. N-butylidenephthalide attenuates Alzheimer's disease-like cytopathy in Down syndrome induced pluripotent stem cell-derived neurons.

    Science.gov (United States)

    Chang, Chia-Yu; Chen, Sheng-Mei; Lu, Huai-En; Lai, Syu-Ming; Lai, Ping-Shan; Shen, Po-Wen; Chen, Pei-Ying; Shen, Ching-I; Harn, Horng-Jyh; Lin, Shinn-Zong; Hwang, Shiaw-Min; Su, Hong-Lin

    2015-03-04

    Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles.

  11. 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)

    Rania M. Bakkar

    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 3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (A42 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 A42 could relate to the cases' similar life-time accumulation of A 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 A42, 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.

  12. 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...

  13. Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE? Polimorfismo da MTHFR é um fator de risco para demência de Alzheimer como APOE?

    Directory of Open Access Journals (Sweden)

    Liana Lisboa Fernandez

    2005-03-01

    Full Text Available BACKGROUND: The role of methylenetetrahydrofolate reductase (MTHFR gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD is still controversial: OBJECTIVE: To verify the association between MTHFR and apolipoprotein E (APOE polymorphisms and Alzheimer's disease. METHOD: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated anlysis adjust by Mantel-Haenszel method. RESULTS: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002 The odds ratio increased exponentially with the increased number of E4 allele (chi2 linear tendency test. No significant difference was detected on MTHFR genotypes in both case and control groups. CONCLUSION: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.INTRODUÇÃO: O papel do polimorfismo do gene da metilenotetrahidrofolato redutase (MTHFR como um fator de risco para demência de Alzheimer (DA é controverso ainda. OBJETIVO: Verificar a associação entre os polimorfismos da MTHFR e apolipoproteína E (APOE e DA. MÉTODO: O trabalho foi conduzido como um estudo caso-controle. Trinta pacientes com DA provável foram incluídos no grupo caso. Vinte e nove indivíduos sem demência comprovadas por testes neuropsicológicos, emparelhados pela idade, sexo, cor e nível educacional constituíram o grupo

  14. 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.

  15. 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.

  16. 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 both groups...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  18. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms.

    Science.gov (United States)

    Lang, Minglin; Fan, Qiangwang; Wang, Lei; Zheng, Yajun; Xiao, Guiran; Wang, Xiaoxi; Wang, Wei; Zhong, Yi; Zhou, Bing

    2013-11-01

    Disruption of copper homeostasis has been implicated in Alzheimer's disease (AD) during the last 2 decades; however, whether copper is a friend or a foe is controversial. Within a genetically tractable Drosophila AD model, we manipulated the expression of human high-affinity copper importer orthologous in Drosophila to explore the in vivo roles of copper ions in the development of AD. We found that inhibition of Ctr1C expression by RNAi in Aβ-expressing flies significantly reduced copper accumulation in the brains of the flies as well as ameliorating neurodegeneration, enhancing climbing ability, and prolonging lifespan. Interestingly, Ctr1C inhibition led to a significant increase in higher-molecular-weight Aβ42 forms in brain lysates, whereas it was accompanied by a trend of decreased expression of amyloid-β degradation proteases (including NEP1-3 and IDE) with age and reduced Cu-Aβ interaction-induced oxidative stress in Ctr1C RNAi flies. Similar results were obtained from inhibiting another copper importer Ctr1B and overexpressing a copper exporter DmATP7 in the nervous system of AD flies. These results imply that copper may play a causative role in developing AD, as either Aβ oligomers or aggregates were less toxic in a reduced copper environment or one with less copper binding. Early manipulation of brain copper uptake can have a great effect on Aβ pathology.

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

    Science.gov (United States)

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    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 (11)C-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.

  20. 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)

  1. TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice.

    Science.gov (United States)

    Devi, L; Ohno, M

    2015-05-05

    Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) significantly decrease early in Alzheimer's disease (AD). However, it remains unclear whether BDNF/TrkB reductions may be mechanistically involved in the pathogenesis of AD. To address this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout (TrkB(+/-)·5XFAD), and tested the effects of TrkB reduction on AD-like features in this mouse model during an incipient stage that shows only modest amyloid-β (Aβ) pathology and retains normal mnemonic function. TrkB(+/-) reduction exacerbated memory declines in 5XFAD mice at 4-5 months of age as assessed by the hippocampus-dependent spontaneous alternation Y-maze task, while the memory performance was not affected in TrkB(+/-) mice. Meanwhile, TrkB(+/-)·5XFAD mice were normal in nest building, a widely used measure for social behavior, suggesting the memory-specific aggravation of AD-associated behavioral impairments. We found no difference between TrkB(+/-)·5XFAD and 5XFAD control mice in cerebral plaque loads, Aβ concentrations including total Aβ42 and soluble oligomers and β-amyloidogenic processing of amyloid precursor protein. Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate receptor subunits as well as impaired signaling pathways downstream to TrkB such as CREB (cAMP response element-binding protein) and Akt/GSK-3β (glycogen synthase kinase-3β) were observed in TrkB(+/-)·5XFAD mice but not in 5XFAD mice. Among these signaling aberrations, only Akt/GSK-3β dysfunction occurred in TrkB(+/-) mice, while others were synergistic consequences between TrkB reduction and subthreshold levels of Aβ in TrkB(+/-)·5XFAD mice. Collectively, our results indicate that reduced TrkB does not affect β-amyloidosis but exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions in early AD.

  2. 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.)

  3. ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

    Science.gov (United States)

    Wang, Jinping; Logovinsky, Veronika; Hendrix, Suzanne B; Stanworth, Stephanie H; Perdomo, Carlos; Xu, Lu; Dhadda, Shobha; Do, Ira; Rabe, Martin; Luthman, Johan; Cummings, Jeffrey; Satlin, Andrew

    2016-01-01

    Background Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. Methods Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients’ early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations. Results ADCOMS consists of 4 Alzheimer's Disease Assessment Scale–cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating—Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials. Conclusions ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD. PMID:27010616

  4. 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

    BACKGROUND: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer's disease (AD). METHODS: Data from 906 patients (388 receiving placebo; 518 receiving...

  5. 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

  6. Alzheimer

    OpenAIRE

    Mons, Ute

    2015-01-01

    Kaum ist die Weihnachtsgans verdaut, stecken wir in den Vorbereitungen für das Sylvester-Menü. Das ist auch gut so, schließlich nimmt man nicht zwischen Weihnachten und Sylvester zu, sondern andersherum: zwischen Sylvester und Weihnachten. Was wir das ganze Jahr über essen, hat massiven Einfluss auf unsere Gesundheit. Forscher der Universität Heidelberg haben jetzt gezeigt, dass unser Lebens-Stil das Risiko senken kann, an Alzheimer zu erkranken. Der Beitrag erschien in der Sendereihe "Ca...

  7. 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

  8. 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.)

  9. 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.

  10. Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons.

    Science.gov (United States)

    Kapasi, A; Schneider, J A

    2016-05-01

    There is growing evidence suggesting that vascular pathologies and dysfunction play a critical role in cognitive impairment, clinical Alzheimer's disease, and dementia. Vascular pathologies such as macroinfarcts, microinfarcts, microbleeds, small and large vessel cerebrovascular disease, and white matter disease are common especially in the brains of older persons where they contribute to cognitive impairment and lower the dementia threshold. Vascular dysfunction resulting in decreased cerebral blood flow, and abnormalities in the blood brain barrier may also contribute to the Alzheimer's disease (AD) pathophysiologic process and AD dementia. This review provides a clinical-pathological perspective on the role of vessel disease, vascular brain injury, alterations of the neurovascular unit, and mixed pathologies in the Alzheimer's disease pathophysiologic process and Alzheimer's dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26769363

  11. 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

  12. AMPA workshop on challenges faced by investigators conducting Alzheimer's disease clinical trials.

    Science.gov (United States)

    Vellas, Bruno; Pesce, Alain; Robert, Philippe H; Aisen, Paul S; Ancoli-Israel, Sonia; Andrieu, Sandrine; Cedarbaum, Jesse; Dubois, Bruno; Siemers, Eric; Spire, Jean-Paul; Weiner, Michael W; May, Thomas S

    2011-07-01

    The recruitment and retention of patients are among the greatest challenges currently being faced by researchers who conduct Alzheimer's disease (AD) clinical trials. To discuss these challenges and other major issues associated with clinical research in AD, an international workshop was organized by the Association Monégasque pour la recherche sur la Maladie d'Alzheimer at Monte Carlo, Monaco, in February 2010, with the participation of leading research experts in the field of Alzheimer's. Key topics discussed were as follows: (1) the selection, recruitment, and retention of clinical trial subjects; (2) international co-operation among researchers; and (3) patient rights and informed consent for participants in clinical trials. This article highlights some of the challenges faced by investigators when conducting clinical trials in AD, and it also offers some recommendations aimed at overcoming these challenges.

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. Effect of Ferulic Acid on Learning-memory and Expression of GFAP in the Hippocampus Tissues of Alzheimer' s Disease-like Model Mice%阿魏酸对拟痴呆小鼠学习记忆和海马胶质 纤维酸性蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    金蓓蓓; 陈勤; 陈庆林

    2011-01-01

    目的:探讨阿魏酸对阿尔茨海默病(AD)模型小鼠神经行为学和海马胶质纤维酸性蛋白(GFAP)表达的影响,分析阿魏酸对小鼠脑的保护作用.方法:海马CA1区注射微量红藻氨酸(KA)建立痴呆模型,然后对痴呆小鼠用不同剂量的阿魏酸(FA)灌胃治疗.Morris水迷宫实验观察小鼠行为学变化,免疫组织化学方法观察GFAP的表达.结果:与假手术组相比,模型组学习记忆能力明显降低(P<0.01)GFAP阳性细胞表达明显增多(P<0.01);与模型组相比,阿魏酸治疗组学习记忆能力均明显提高(P<O.01),GFAP阳性细胞表达均明显减少(P<0.01).结论:用不同剂量的阿魏酸治疗拟AD小鼠后,小鼠学习记忆能力得到明显改善,GFAP表达得到明显抑制,起到保护脑的作用.%Objective: To investigate the effects of ferulic acid on neurological behavior and the expression of glial fibril-lary acidic protein(GFAP) of hippocampus tissues in Alzheimer' s disease-like model mice, and to analyze the protective effects of ferulic acid on the brain. Methods: kainic acid ( KA) was injected into hippocampus CA1 region of mice and to establish Alzheimer' s disease-like model, then the drug group with different doses of ferulic acid gavage lasted a month. The learning and memory abilities of the mice were assessed through Morris water maze behavioral test, and GFAP were observed by immunohistochemistry respectively. Results: Compared with the normal group, the abilities of learning and memory of the mice in the model group significantly decreased (P < 0.01 ) and the expression of GFAP in the CA1 region were increased(P<0.01). Compared with the model group, the abilities of learning and memory of the mice in the ferulic acid group improved ( P < 0. 01 ) and the expressions of GFAP in the CA1 region decreased ( P < 0.01). Conclusion: The different doses of ferulic acid dealing with the Alzheimer disease-like model mice can improve the abilities of learning

  18. 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)

  19. 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

  20. 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

  1. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Sei J Lee

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Johnstone

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

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

    Science.gov (United States)

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

    2016-09-01

    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

  5. 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 ...

  6. 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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  8. Odor identification and Alzheimer disease biomarkers in clinically normal elderly

    Science.gov (United States)

    Growdon, Matthew E.; Schultz, Aaron P.; Dagley, Alexander S.; Amariglio, Rebecca E.; Hedden, Trey; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Albers, Mark W.

    2015-01-01

    Objectives: Our objective was to investigate cross-sectional associations between odor identification ability and imaging biomarkers of neurodegeneration and amyloid deposition in clinically normal (CN) elderly individuals, specifically testing the hypothesis that there may be an interaction between amyloid deposition and neurodegeneration in predicting odor identification dysfunction. Methods: Data were collected on 215 CN participants from the Harvard Aging Brain Study. Measurements included the 40-item University of Pennsylvania Smell Identification Test and neuropsychological testing, hippocampal volume (HV) and entorhinal cortex (EC) thickness from MRI, and amyloid burden using Pittsburgh compound B (PiB) PET. A linear regression model with backward elimination (p < 0.05 retention) evaluated the cross-sectional association between the University of Pennsylvania Smell Identification Test and amyloid burden, HV, and EC thickness, assessing for effect modification by PiB status. Covariates included age, sex, premorbid intelligence, APOE ε4 carrier status, and Boston Naming Test. Results: In unadjusted univariate analyses, worse olfaction was associated with decreased HV (p < 0.001), thinner EC (p = 0.003), worse episodic memory (p = 0.03), and marginally associated with greater amyloid burden (binary PiB status, p = 0.06). In the multivariate model, thinner EC in PiB-positive individuals (interaction term) was associated with worse olfaction (p = 0.02). Conclusions: In CN elderly, worse odor identification was associated with markers of neurodegeneration. Furthermore, individuals with elevated cortical amyloid and thinner EC exhibited worse odor identification, elucidating the potential contribution of olfactory testing to detect preclinical AD in CN individuals. PMID:25934852

  9. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

    Science.gov (United States)

    Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin

    2016-01-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

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

    Science.gov (United States)

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

    2016-08-01

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

  11. 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

  12. 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

  13. Evolution of neurodegeneration-imaging biomarkers from clinically normal to dementia in the Alzheimer disease spectrum.

    Science.gov (United States)

    Knopman, David S; Jack, Clifford R; Lundt, Emily S; Weigand, Stephen D; Vemuri, Prashanthi; Lowe, Val J; Kantarci, Kejal; Gunter, Jeffrey L; Senjem, Matthew L; Mielke, Michelle M; Machulda, Mary M; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald C

    2016-10-01

    The availability of antemortem biomarkers for Alzheimer's disease (AD) enables monitoring the evolution of neurodegenerative processes in real time. Pittsburgh compound B (PIB) positron emission tomography (PET) was used to select participants in the Mayo Clinic Study of Aging and the Mayo Alzheimer's Disease Research Center with elevated β-amyloid, designated as "A+," and hippocampal volume and (18)fluorodeoxyglucose (FDG) positron emission tomography were used to characterize participants as having evidence of neurodegeneration ("N+") at the baseline evaluation. There were 145 clinically normal (CN) A+ individuals, 62 persons with mild cognitive impairment (MCI) who were A+ and 20 with A+ AD dementia. Over a period of 1-6 years, MCI A+N+ individuals showed declines in medial temporal, lateral temporal, lateral parietal, and to a lesser extent, medial parietal regions for both FDG standardized uptake value ratio and gray matter volume that exceeded declines seen in the CN A+N+ group. The AD dementia group showed declines in the same regions on FDG standardized uptake value ratio and gray matter volume with rates that exceeded that in MCI A+N+. Expansion of regional involvement and faster rate of neurodegeneration characterizes progression in the AD pathway. PMID:27460147

  14. γ-Hydroxybutyrate (Xyrem) ameliorates clinical symptoms and neuropathology in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Klein, Christian; Mathis, Chantal; Leva, Géraldine; Patte-Mensah, Christine; Cassel, Jean-Christophe; Maitre, Michel; Mensah-Nyagan, Ayikoe G

    2015-02-01

    The chronic decrease of brain amyloid-β (Aβ) peptides is an emerging therapeutic for Alzheimer's disease, but no such treatment has achieved clinical validation yet. In vivo, some brain proteases, including neprilysin, possess the ability of degrading Aβ and experimental data suggest their exploitation in strategies to reduce cerebral Aβ concentration. Previous studies have shown that pharmacologic doses of gamma-hydroxybutyrate (sodium oxybate or Xyrem) induce histone deacetylases (HDACs) inhibition and neprilysin gene expression. Here, we demonstrate that brain neprilysin overexpression induced in vivo by repeated gamma-hydroxybutyrate autoadministration reduces cerebral Aβ contents and prevents cognitive deficits in APPSWE mice. Oral gamma-hydroxybutyrate also counteracted phosphoramidon-induced brain neprilysin inhibition and Aβ accumulation. HDACs activities in SH-SY5Y cells were inhibited by gamma-hydroxybutyrate which did not affect amyloid peptide precursor intracellular domain. Together, our results suggest that gamma-hydroxybutyrate, acting via HDAC inhibition, upregulates neprilysin to reduce Aβ level and related memory deficits. Because gamma-hydroxybutyrate doses used herein are clinically relevant, our data suggest that chronic oral administration of gamma-hydroxybutyrate or its analogs may be considered for strategies against presymptomatic or established Alzheimer's disease.

  15. Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Tomoyuki Nagata

    2015-03-01

    Full Text Available Background/Aims: In the present study, we examined whether DNA methylation of the brain-derived neurotrophic factor (BDNF promoter is associated with the manifestation and clinical presentation of Alzheimer's disease (AD. Methods: Of 20 patients with AD and 20 age-matched normal controls (NCs, the DNA methylation of the BDNF promoter (measured using peripheral blood samples was completely analyzed in 12 patients with AD and 6 NCs. The resulting methylation levels were compared statistically. Next, we investigated the correlation between the DNA methylation levels and the clinical presentation of AD. Results: The total methylation ratio (in % of the 20 CpG sites was significantly higher in the AD patients (5.08 ± 5.52% than in the NCs (2.09 ± 0.81%; p Conclusion: These results suggest that the DNA methylation of the BDNF promoter may significantly influence the manifestation of AD and might be associated with its neurocognitive presentation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Takita, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1996-08-01

    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)

  17. Couples Counseling in Alzheimer's Disease: Additional Clinical Findings from a Novel Intervention Study.

    Science.gov (United States)

    Auclair, Ursula; Epstein, Cynthia; Mittelman, Mary

    2009-04-01

    This article describes the clinical findings of a study designed to assess the benefit of counseling for couples, one of whom is in the early stage of Alzheimer's disease (AD). We previously reported our findings based on the first 12 couples that enrolled in the study. Based on the treatment of 30 additional couples, we have refined our treatment strategy to include concepts of Gestalt Therapy and Transactional Analysis and identified prevalent issues of concern to this cohort. The study design has remained as described in the earlier article (Epstein et al., 2006), and has proven to be appropriate to meet the goals of this intervention as indicated by our clinical experience and feedback from the participating couples. Case vignettes demonstrate how to conduct the sessions so that the experience of each member of the dyad is validated, while acknowledging the differential impact of the disease on them. PMID:19865591

  18. 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...

  19. Alzheimer - resources

    Science.gov (United States)

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

  20. 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 ...

  1. 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)

  2. 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...

  3. 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

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

    Science.gov (United States)

    Zhagn, Lili; Li, Zhiping

    2014-09-01

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

  5. 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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  7. 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.

  8. 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 ...

  9. 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.

  10. Alzheimer's Project

    Medline Plus

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

  11. 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," ...

  12. 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 ...

  13. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    Science.gov (United States)

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  14. Clinical significance of sleep-disordered breathing in Alzheimer's disease. Preliminary data.

    Science.gov (United States)

    Hoch, C C; Reynolds, C F; Nebes, R D; Kupfer, D J; Berman, S R; Campbell, D

    1989-02-01

    In a study of 15 probable Alzheimer's patients and 12 healthy elderly control subjects, Alzheimer's patients had a significantly higher apnea index (patients versus controls, mean +/- SD: 6.3 +/- 6.6 vs 1.8 +/- 2.7, P less than .05) and greater maximal duration of apnea (patients versus controls, median: 50.0 vs 28.5 seconds, P less than .001), but no significant increase in oxyhemoglobin desaturation compared with controls. (The accepted normal threshold for abnormality is an apnea index more than 5.) Although three of seven psychometric tests (odd-even, category retrieval, face-hand test) showed diurnal effects on one or more of their subscores, with Alzheimer's patients having significantly poorer scores at the AM than at PM testing, overnight change scores in the psychometric tests were not significantly correlated with severity of sleep-disordered breathing. Further, only 18.1% of the disruptive (ie, requiring intervention) nocturnal behaviors of the Alzheimer's patients were temporally linked to sleep-disordered breathing. The current data suggest that sleep-disordered breathing in nonmedicated Alzheimer's patients is relatively mild and is not a predictor of either overnight mental status changes, of disruptive nocturnal behaviors, or of daytime behavioral fluctuations. Additional studies of more severely demented patients and possibly of sleeping pill effects would be useful in further evaluating the role of sleep apnea in Alzheimer behavioral changes. PMID:2910971

  15. Clinical significance of sleep-disordered breathing in Alzheimer's disease. Preliminary data.

    Science.gov (United States)

    Hoch, C C; Reynolds, C F; Nebes, R D; Kupfer, D J; Berman, S R; Campbell, D

    1989-02-01

    In a study of 15 probable Alzheimer's patients and 12 healthy elderly control subjects, Alzheimer's patients had a significantly higher apnea index (patients versus controls, mean +/- SD: 6.3 +/- 6.6 vs 1.8 +/- 2.7, P less than .05) and greater maximal duration of apnea (patients versus controls, median: 50.0 vs 28.5 seconds, P less than .001), but no significant increase in oxyhemoglobin desaturation compared with controls. (The accepted normal threshold for abnormality is an apnea index more than 5.) Although three of seven psychometric tests (odd-even, category retrieval, face-hand test) showed diurnal effects on one or more of their subscores, with Alzheimer's patients having significantly poorer scores at the AM than at PM testing, overnight change scores in the psychometric tests were not significantly correlated with severity of sleep-disordered breathing. Further, only 18.1% of the disruptive (ie, requiring intervention) nocturnal behaviors of the Alzheimer's patients were temporally linked to sleep-disordered breathing. The current data suggest that sleep-disordered breathing in nonmedicated Alzheimer's patients is relatively mild and is not a predictor of either overnight mental status changes, of disruptive nocturnal behaviors, or of daytime behavioral fluctuations. Additional studies of more severely demented patients and possibly of sleeping pill effects would be useful in further evaluating the role of sleep apnea in Alzheimer behavioral changes.

  16. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

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

  17. Performance Evaluation of an Automated ELISA System for Alzheimer's Disease Detection in Clinical Routine.

    Science.gov (United States)

    Chiasserini, Davide; Biscetti, Leonardo; Farotti, Lucia; Eusebi, Paolo; Salvadori, Nicola; Lisetti, Viviana; Baschieri, Francesca; Chipi, Elena; Frattini, Giulia; Stoops, Erik; Vanderstichele, Hugo; Calabresi, Paolo; Parnetti, Lucilla

    2016-07-22

    The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers undermines their full-fledged introduction into routine diagnostics and clinical trials. Automation may help to increase precision and decrease operator errors, eventually improving the diagnostic performance. Here we evaluated three new CSF immunoassays, EUROIMMUNtrademark amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and total tau (t-tau), in combination with automated analysis of the samples. The CSF biomarkers were measured in a cohort consisting of AD patients (n = 28), mild cognitive impairment (MCI, n = 77), and neurological controls (OND, n = 35). MCI patients were evaluated yearly and cognitive functions were assessed by Mini-Mental State Examination. The patients clinically diagnosed with AD and MCI were classified according to the CSF biomarkers profile following NIA-AA criteria and the Erlangen score. Technical evaluation of the immunoassays was performed together with the calculation of their diagnostic performance. Furthermore, the results for EUROIMMUN Aβ1-42 and t-tau were compared to standard immunoassay methods (INNOTESTtrademark). EUROIMMUN assays for Aβ1-42 and t-tau correlated with INNOTEST (r = 0.83, p < 0.001 for both) and allowed a similar interpretation of the CSF profiles. The Aβ1-42/Aβ1-40 ratio measured with EUROIMMUN was the best parameter for AD detection and improved the diagnostic accuracy of Aβ1-42 (area under the curve = 0.93). In MCI patients, the Aβ1-42/Aβ1-40 ratio was associated with cognitive decline and clinical progression to AD.The diagnostic performance of the EUROIMMUN assays with automation is comparable to other currently used methods. The variability of the method and the value of the Aβ1-42/Aβ1-40 ratio in AD diagnosis need to be validated in large multi-center studies. PMID:27447425

  18. Alzheimer's disease

    OpenAIRE

    Schachter, Armand S.; Davis, Kenneth L.

    2000-01-01

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

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

    NARCIS (Netherlands)

    Farkas, E; Luiten, PGM

    2001-01-01

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

  20. 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

  1. 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…

  2. 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.

  3. 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 . ...

  4. Alzheimer's Project

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    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 ...

  5. 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, ...

  6. Alzheimer disease

    Science.gov (United States)

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

  7. 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…

  8. 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...

  9. 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

  10. 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...

  11. 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...

  12. 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

  13. 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 ...

  14. 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

  15. 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)

  16. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

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

    2011-01-01

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

  17. NIA-funded Alzheimer centers are more efficient than commercial clinical recruitment sites for conducting secondary prevention trials of dementia.

    Science.gov (United States)

    Edland, Steven D; Emond, Jennifer A; Aisen, Paul S; Petersen, Ronald C

    2010-01-01

    Study participant dropout compromises clinical trials by reducing statistical power and potentially biasing findings. We use data from a trial of treatments to delay the progression of mild cognitive impairment to Alzheimer disease (AD) [NEJM 2005;352 (23):79 to 88] to determine predictors of study participant dropout and inform the design and implementation of future trials. Time to study discontinuation was modeled by proportional hazards regression with censoring at incident dementia or trial completion. Of 769 participants, 230 (30%) discontinued prematurely. Risk of dropout was higher among nonwhites [hazard ratio (HR) 2.1, P=0.0007], participants with less than college education (HR=1.6, P=0.02), participants with a Hamilton Depression score of 6 or more (HR=1.3, P=0.04), unmarried males (HR=2.1 relative to married males, P=0.003) and participants recruited by commercial clinical sites (HR=2.2 relative to participants recruited by NIA-funded AD research centers, Prates and incident dementia event rates experienced in this trial would require 80% more participants than a comparably powered trial using NIA-funded AD research center sites. Targeted retention efforts and utilization of academic sites could substantively improve the statistical power and validity of future clinical trials of cognitively impaired elderly. PMID:20505433

  18. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease.

    Science.gov (United States)

    Jeppsson, Fredrik; Eketjäll, Susanna; Janson, Juliette; Karlström, Sofia; Gustavsson, Susanne; Olsson, Lise-Lotte; Radesäter, Ann-Cathrine; Ploeger, Bart; Cebers, Gvido; Kolmodin, Karin; Swahn, Britt-Marie; von Berg, Stefan; Bueters, Tjerk; Fälting, Johanna

    2012-11-30

    β-Site amyloid precursor protein cleaving enzyme1 (BACE1) is one of the key enzymes involved in the processing of the amyloid precursor protein (APP) and formation of amyloid β peptide (Aβ) species. Because cerebral deposition of Aβ species might be critical for the pathogenesis of Alzheimer disease, BACE1 has emerged as a key target for the treatment of this disease. Here, we report the discovery and comprehensive preclinical characterization of AZD3839, a potent and selective inhibitor of human BACE1. AZD3839 was identified using fragment-based screening and structure-based design. In a concentration-dependent manner, AZD3839 inhibited BACE1 activity in a biochemical fluorescence resonance energy transfer (FRET) assay, Aβ and sAPPβ release from modified and wild-type human SH-SY5Y cells and mouse N2A cells as well as from mouse and guinea pig primary cortical neurons. Selectivity against BACE2 and cathepsin D was 14 and >1000-fold, respectively. AZD3839 exhibited dose- and time-dependent lowering of plasma, brain, and cerebrospinal fluid Aβ levels in mouse, guinea pig, and non-human primate. Pharmacokinetic/pharmacodynamic analyses of mouse and guinea pig data showed a good correlation between the potency of AZD3839 in primary cortical neurons and in vivo brain effects. These results suggest that AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species. It might, therefore, have disease-modifying potential in the treatment of Alzheimer disease and related dementias. Based on the overall pharmacological profile and its drug like properties, AZD3839 has been progressed into Phase 1 clinical trials in man.

  19. 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. ...

  20. Alzheimer's Project

    Medline Plus

    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

    Medline Plus

    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

    Medline Plus

    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 ® ...

  3. 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: * ...

  4. Alzheimer's Project

    Medline Plus

    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 ...

  5. 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 ...

  6. Alzheimer's Project

    Medline Plus

    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 ...

  7. 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 ...

  8. Alzheimer's Project

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    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 ...

  9. 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 Project MAKE ... for kids Learn how Maria Shriver is raising awareness '; jQuery('#luminateApi').hide(); jQuery('#otherLinks').show(); jQuery('#TRByZip'). ...

  10. 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

  11. 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...

  12. Clinical research of Alzheimer,s disease complicated with Epilepsy%阿尔茨海默病伴发癫痫临床分析

    Institute of Scientific and Technical Information of China (English)

    赵爱云; 崔群力

    2014-01-01

    Objective To explore the incidence rate of epilepsy secondary to Alzheimer ,s disease (AD)、its pathogenesis、clinical treatment and its effect on AD. Methods the data of 120 patients with AD from 2000-2012 were retrospectively ana-lyzed ,the incidence rate of Epilepsy secondary to AD was analyzed. 19 AD patients complicated with Epilepsy were classified to the observation group ,101 AD patients without Epilepsy to the control group. And then the clinical treatment and accessory examinations of 19 AD patients complicated with Epilepsy and the effect of Epilepsy on AD were analyzed. Results Among the 120 AD patients ,19 cases were complicated with Epilepsy (15.8% ) ,Among which ,7 cases occurred in early stage ,3 cases in middle ,9 cases in late ;according to the seizure types of Epilepsy ,they included :8 cases of generalized tonic-clonic seizure ,13 cases of complex partial seizures ,2 cases of simple partial seizure. 2 cases of the 19 patients had status epilepticus ;Mean age of AD patients with Epilepsy was less than that of AD without Epilepsy (P<0.05) ,mean survival time of AD patients with Epi-lepsy was shorter than that of those without Epilepsy (P<0.05) ;Brain atrophy was significantly obvious in AD with Epilepsy group ;The antiepileptic drug was not very effective in controlling the Epileptic seizure in patients with AD ,The frequency of Epileptic seizures increased as the symptoms of AD exacerbated. Conclusion The incidence rate of Epilepsy in AD is 15.8%.Epilepsy may occur at any time in AD ,mean age of onset of Epilepsy in AD is small ,mean survival time is short. Epilepsy can worsen AD symptoms and shorten the survival time of AD. The pathogenesis of Epilepsy in AD is associated with loss of neu-rons ,temporal lobe and hippocampal sclerosis. The antiepileptic drug is not very effective in controlling the Epileptic seizure in patients w ith AD.%目的:探讨阿尔茨海默病(AD )伴发癫痫的发生率、机制、临床治疗及癫痫对AD病

  13. Cerebrolysin in Alzheimer's disease.

    Science.gov (United States)

    Antón Álvarez, X; Fuentes, Patricio

    2011-07-01

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

  14. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

    Science.gov (United States)

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

  15. 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.

  16. 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

  17. Neuroinflammation in Alzheimer's disease wanes with age

    Directory of Open Access Journals (Sweden)

    Hoozemans Jeroen JM

    2011-12-01

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

  18. 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...

  19. Clinical Observation of Acupuncture-moxibustion for Alzheimer ’s Disease

    Institute of Scientific and Technical Information of China (English)

    Cui Li

    2014-01-01

    Objective:To observe the clinical efficacy of acupuncture-moxibustion in treating Alzheimer’s disease (AD). Methods: Forty-eight eligible AD patients were enrolled to receive acupuncture plus herb-partitioned moxibustion. Mini-mental state examination (MMSE) was adopted for evaluation before and after intervention, and the therapeutic efficacy was observed. Results: After intervention, the MMSE score changed significantly (P Conclusion: Acupuncture-moxibustion can significantly improve the cognitive function of AD patients, beneficial to the general promotion of the quality of life.

  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 ... 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. ...

  2. Alzheimer's Project

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    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 ...

  3. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Aderbal R T Silva

    Full Text Available Alzheimer's disease (AD is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles. Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX, DNA repair (p53, BRCA1, PTEN, and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1 through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA composed of three groups: I "clinical-pathological AD" (CP-AD--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C and clinical dementia (CDR ≥ 2, IQCODE>3.8; II "pathological AD" (P-AD--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C and without cognitive impairment (CDR 0, IQCODE<3.2; and III "normal aging" (N--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A and with normal cognitive function (CDR 0, IQCODE<3.2. Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.

  4. Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

    DEFF Research Database (Denmark)

    Jones, Roy W; Schwam, Elias; Wilkinson, David;

    2009-01-01

    Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

  5. Alzheimer's disease.

    Science.gov (United States)

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

    2012-01-01

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

  6. 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.).

  7. 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.)

  8. Alzheimer's Disease

    Science.gov (United States)

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

  9. Alzheimer's Project

    Medline Plus

    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 ...

  10. Alzheimer's Project

    Medline Plus

    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 ...

  11. 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 ...

  12. 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 ...

  13. 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 ...

  14. Alzheimer's Project

    Medline Plus

    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 ...

  15. Penyakit Alzheimer

    OpenAIRE

    Iskandar Japardi

    2002-01-01

    Penyakit alzheimer ditemukan pertama kali pada tahun 1907 oleh seorang ahli Psikiatri dan neuropatologi yang bernama Alois Alzheimer. Ia mengobservasi seorang wanita berumur 51 tahun, yang mengalami gangguan intelektual dan memori serta tidak mengetahui kembali ketempat tinggalnya, sedangkan wanita itu tidak mengalami gangguan anggota gerak,koordinasi dan reflek. Pada autopsi tampak bagian otak mengalami atropi yang difus dan simetri, dan secara nikroskopik tampak bagian kortikal otak mengala...

  16. 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.)

  17. 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.)

  18. 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.

  19. 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

  20. [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

  1. 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 ...

  2. Alzheimer's Project

    Medline Plus

    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 = ...

  3. 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's disease...

  4. 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)

  5. Harmonized diagnostic criteria for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  6. 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

  7. 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....

  8. 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, ...

  9. Cognitive aging and Alzheimer's disease

    OpenAIRE

    Vandenberghe, R; Tournoy, J.

    2005-01-01

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

  10. Hypertension in patients with Alzheimer's disease--prevalence, characteristics, and impact on clinical outcome. Experience of one neurology center in Poland.

    Science.gov (United States)

    Warchol-Celinska, Ewa; Styczynska, Maria; Prejbisz, Aleksander; Przybylowska, Katarzyna; Chodakowska-Zebrowska, Malgorzata; Kurjata, Pawel; Piotrowski, Walerian; Polakowska, Maria; Kabat, Marek; Zdrojewski, Tomasz; Drygas, Wojciech; Januszewicz, Andrzej; Barcikowska, Maria

    2015-09-01

    The aim of the study was to evaluate hypertension (HT) prevalence, characteristics, and impact on clinical outcome in patients with Alzheimer's disease (AD). We evaluated 701 patients with AD (249 males, 452 females, and mean age 74.9 ± 7.5 years). As a group representing general population matched with regard to age, education level, and place of residence, we included 762 subjects (438 males, 324 females, and mean age 74.7 ± 4.4 years) from the Polish National Multicenter Health Survey (WOBASZ) studies. The patients with AD were characterized by lower systolic blood pressure (BP) and diastolic BP values (134 ± 21 vs. 151 ± 23 mm Hg, P < .001 and 77 ± 11 vs. 86 ± 12 mm Hg, P < .001, respectively) as well as lower HT prevalence (66% vs. 78.6%, P < .001) compared with the WOBASZ group. In long-term follow-up of AD group, HT and BP levels were not associated with the decline in cognitive functions nor the increased risk of death. Patients with AD were characterized by lower prevalence of HT and other vascular risk factors. BP levels and HT had no impact on clinical outcome. PMID:26210391

  11. Apolipoprotein E as a Therapeutic Target in Alzheimer's Disease: A Review of Basic Research and Clinical Evidence.

    Science.gov (United States)

    Yamazaki, Yu; Painter, Meghan M; Bu, Guojun; Kanekiyo, Takahisa

    2016-09-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disorder that causes progressive cognitive decline. The majority of AD cases are sporadic and late-onset (>65 years old) making it the leading cause of dementia in the elderly. While both genetic and environmental factors contribute to the development of late-onset AD (LOAD), APOE polymorphism is a major genetic risk determinant for LOAD. In humans, the APOE gene has three major allelic variants: ε2, ε3, and ε4, of which APOE ε4 is the strongest genetic risk factor for LOAD, whereas APOE ε2 is protective. Mounting evidence suggests that APOE ε4 contributes to AD pathogenesis through multiple pathways including facilitated amyloid-β deposition, increased tangle formation, synaptic dysfunction, exacerbated neuroinflammation, and cerebrovascular defects. Since APOE modulates multiple biological processes through its corresponding protein apolipoprotein E (apoE), APOE gene and apoE properties have been a promising target for therapy and drug development against AD. In this review, we summarize the current evidence regarding how the APOE ε4 allele contributes to the pathogenesis of AD and how relevant therapeutic approaches can be developed to target apoE-mediated pathways in AD. PMID:27328687

  12. 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...

  13. Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Rojo, Leonel E; Alzate-Morales, Jans; Saavedra, Iván N; Davies, Peter; Maccioni, Ricardo B

    2010-01-01

    We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these compounds, with important medical applications in the treatment of allergies and gastrointestinal disorders respectively, specifically bind to aggregated variants of tau protein and to paired helical filaments isolated from brains of Alzheimer's disease (AD) patients. These ligands appear to be a powerful tool to tag brain-isolated tau-aggregates and heparin-induced polymers of recombinant tau. The interactions of AST and LNS with tau aggregates were assessed by classical radioligand assays, surface plasmon resonance, and bioinformatic approaches. The affinity of AST and LNS for tau aggregates was comparatively higher than that for amyloid-beta polymers according to our data. This is relevant since senile plaques are also abundant but are not pathognomonic in AD patients. Immunochemical studies on paired helical filaments from brains of AD patients and surface plasmon resonance studies confirm these findings. The capacity of these drugs to penetrate the blood-brain barrier was evaluated: i) in vitro by parallel artificial membrane permeability assay followed by experimental Log P determinations; and ii) in vivo by pharmacokinetic studies comparing distribution profiles in blood and brain of mice using HPLC/UV. Importantly, our studies indicate that the brain/blood concentration ratios for these compounds were suitable for their use as PET radiotracers. Since neurofibrillary tangles are positively correlated with cognitive impairment, we concluded that LNS and AST have a great potential in PET neuroimaing for in vivo early detection of AD and in reducing the formation of neurofibrillary tangles. PMID:20110603

  14. 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.

  15. 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

  16. 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

  17. Clinical Recommendations for the Use of Donepezil 23 mg in Moderate-to-Severe Alzheimer's Disease in the Asia-Pacific Region

    Science.gov (United States)

    Sabbagh, Marwan; Han, SeolHeui; Kim, SangYun; Na, Hae-Ri; Lee, Jae-Hong; Kandiah, Nagaendran; Phanthumchinda, Kammant; Suthisisang, Chuthamanee; Senanarong, Vorapun; Pai, Ming-Chyi; Narilastri, Diatri; Sowani, Ajit M.; Ampil, Encarnita; Dash, Amitabh

    2016-01-01

    Background The ‘Asia-Pacific Expert Panel (APEX) for donepezil 23 mg’ met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD). Summary In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p < 0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that the benefits and risks associated with donepezil 23 mg/day versus donepezil 10 mg/day in Asian patients with moderate-to-severe AD were comparable to those in the global study population. Key Message Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications), a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD. PMID:27703471

  18. Clinical Recommendations for the Use of Donepezil 23 mg in Moderate-to-Severe Alzheimer's Disease in the Asia-Pacific Region

    Directory of Open Access Journals (Sweden)

    Marwan Sabbagh

    2016-09-01

    Full Text Available Background: The ‘Asia-Pacific Expert Panel (APEX for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD. Summary: In a global phase III study (study 326 in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p Key Message: Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications, a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD.

  19. Association between high biomarker probability of Alzheimer's disease and improvement of clinical outcomes after shunt surgery in patients with idiopathic normal pressure hydrocephalus.

    Science.gov (United States)

    Kazui, Hiroaki; Kanemoto, Hideki; Yoshiyama, Kenji; Kishima, Haruhiko; Suzuki, Yukiko; Sato, Shunsuke; Suehiro, Takashi; Azuma, Shingo; Yoshimine, Toshiki; Tanaka, Toshihisa

    2016-10-15

    We examined the effect of the pathology of Alzheimer's disease (AD) on improvement of clinical symptoms after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Forty-four iNPH patients were classified into 18 patients with (iNPH/AD+) and 26 patients without (iNPH/AD-) combination with low amyloid β42 and high total tau in cerebrospinal fluid (CSF). We compared improvements after lumbo-peritoneal shunt surgery (LPS) between the two groups in Timed Up & Go Test, 10-m reciprocating walking test, Digit Symbol Substitution Test, attention test, delayed recall test, Mini-Mental State Examination, iNPH grading scale, Neuropsychiatric Inventory, Zarit Burden Interview, and other evaluations. Three months after LPS, gait, urination, overall cognition, psychomotor speed, attention, and neuropsychiatric symptoms significantly improved in both groups, but the improvement in delayed recall and reduction of caregiver burden were significantly greater in iNPH/AD- than iNPH/AD+. In addition, improvement in delayed recall score after LPS was significantly and negatively correlated with the probability of AD as judged by amyloid β42 and total tau levels in CSF. Three months after LPS, almost all of the triad symptoms decreased in iNPH patients with and without AD pathology but memory improved only in iNPH patients without AD pathology. PMID:27653897

  20. 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.)

  1. Recent developments in Alzheimer's disease therapeutics

    Directory of Open Access Journals (Sweden)

    Aisen Paul S

    2009-02-01

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

  2. 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.)

  3. 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

    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...

  4. 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...

  5. Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Quattropani, Maria C; Calapai, Fabrizio; Gangemi, Sebastiano; Calapai, Gioacchino

    2014-06-01

    Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials.

  6. 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: ...

  7. 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: ...

  8. 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 ...

  9. The Alzheimer's Project

    Science.gov (United States)

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

  10. 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)

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

    Science.gov (United States)

    Pinzer, B. R.; Cacquevel, M.; Modregger, P.; Thuering, T.; Stampanoni, M.

    2013-05-01

    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.

  12. 中医药治疗阿尔茨海默病临床试验文献评价%literature appraisement of clinical trials in TCM treatment of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    于琦; 崔蒙; 李园白; 尹爱宁

    2011-01-01

    目的:评价中医药治疗阿尔茨海默病临床试验文献的质量.方法:检索1997-2006年国内生物医学期刊和会议论著发表的有关中医药治疗阿尔茨海默病的临床试验文献,收集文献信息,进行描述性分析和一致性检验.结果:共纳入病例数大于10例的临床文献201篇.对文献的一般情况、研究方法情况、研究分组情况、中医药辨证分型及证候分类、药方剂型、药物信息、干预方式、疗效评价标准、样本量等几个方面进行分析.结论:中医药治疗阿尔茨海默病的临床文献质量呈增高趋势,设计日趋严谨.但亦有不足,当根据中医药的特色,规范严谨的制定临床方案,使临床研究结果准确可靠,使中医药治疗阿尔茨海默病的结果得到广泛认可.%Objective: To evaluate the quality of medical treatment on Alzheimer's Disease Clinical Trials. Methods:Retrieving the Chinese medicine treatment of Alzheimer's disease clinical trial literature in biomedical journals from 1997 to 2006. Collecting literature information, carrying descriptive analysis and consistency check. Results: Adopting 201 articles of clinical literature in which the number of case are more than 10 to analyze general literature, research methods, research grouping,TCM Syndrome Differentiation type and classification, prescription dosage, drug information, intervention, criteria of efficacy evaluation, sample size, and several other aspects. Conclusion: Medical treatment of Alzheimer's disease showed an increasing trend in the quality of the clinical literature, stringent experimental design. Rigorous specifications of the clinical program should be developed based on the characteristics of Chinese medicine so that clinical research will be accurate and reliable, and the results of medical treatment of Alzheimer's disease is widely recognized.

  13. Alzheimer's Disease Beyond Abeta.

    Science.gov (United States)

    Town, Terrence

    2010-05-01

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

  14. 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

  15. 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.)

  16. 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

  17. Immunotherapy for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  18. 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...

  19. 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

  20. HEAD TRAUMA AND THE RISK OF ALZHEIMERS-DISEASE

    NARCIS (Netherlands)

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

    1992-01-01

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

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

    NARCIS (Netherlands)

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

    1992-01-01

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

  2. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    Science.gov (United States)

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  3. 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.

  4. 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 ...

  5. 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 ...

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

  7. Biomarkers for early detection of Alzheimer disease.

    Science.gov (United States)

    Barber, Robert C

    2010-09-01

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

  8. 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

  9. 石杉碱甲治疗阿尔茨海默病的临床研究现状%Clinical research status of huperzine A for the treatment of Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    王怀荟; 刘万卉; 孙雯

    2011-01-01

    Huperzine A is a new lycopodium alkaloid isolated from Chinese herb Huperzia serrate. As a reversible cholinesterase (AChE) inhibitor, it has been used for the treatment of Alzheimer's disease, vascular dementia, benign memory disorders etc. for more than sixteen years. In this review, we searched all the published clinical trials with treatment period no less than 12 weeks and sorted them by randomized placebo-controlled trials,randomized positive controlled trials and combination treatment trials of huperzine A for the treatment of Alzheimer's disease. After systematic review, we summarized the efficacy and safety of huperzine A for the treatment of Alzheimer's disease, and also raised the problems in these published trials, including short trial courses, few trial samples and the lack of representativeness of positive controls. Some suggestions and perspectives for the future clinical trials of huperzine A in the treatment of Alzheimer's disease were also proposed in this review.%石杉碱甲是从草药千层塔中分离得到的一种石松类生物碱,作为乙酰胆碱酯酶抑制剂治疗阿尔茨海默病、血管性痴呆、良性记忆障碍等已有超过16年的临床应用经验.本文检索了公开发表的石杉碱甲治疗阿尔茨海默病的临床研究文献,对于疗程不短于12周的研究按随机安慰剂对照试验、随机阳性药对照试验及协同给药试验分类进行了汇总分析,综述了石杉碱甲治疗阿尔茨海默病的疗效和安全性,同时指出了目前石杉碱甲治疗阿尔茨海默病的研究文献中存在的问题,包括试验疗程偏短、样本量偏小、阳性对照药选择代表性不强等,并对未来的工作提出了建议和展望.

  10. Clinical observation of psychological intervention for Alzheimer disease dementia early mild depression%心理干预对于阿尔茨海默病痴呆早期轻度抑郁症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    马忠金; 孟凡莲; 张玉; 张沧霞; 郑艳霞; 邓志云

    2015-01-01

    目的:探讨心理干预对于阿尔茨海默病痴呆早期伴有轻度抑郁症的疗效观察。方法把我院于2010年1月至2012年1月神经内科诊治的60例阿尔茨海默病痴呆早期伴有轻度抑郁症的患者分为2组,每组30例。对照组采用常规治疗(一般支持治疗和药物治疗)。治疗组在常规治疗的基础上加用心理干预疗法。6个月后观察2组AD痴呆患者抑郁症治疗疗效。结果采用心理干预治疗组效果明显好于常规治疗组,两组间存在明显的差异,具有统计学意义(0.01<P<0.05)。结论心理干预对于阿尔茨海默病痴呆早期轻度抑郁症患者的疗效显著,从而可提高患者的生存质量,在临床工作中应该加以推广。%Objective To explore clinical observation of psychological intervention for Alzheimer disease de-mentia early mild depression.Methods Sixty patients with Alzheimer disease dementia early mild depression in our hospital from 2011 January to 2012 January in department and internal medicine diagnosis and treatment were divided in-to treatment group and control group with 30 cases in each group.Treatment group adopted conventional therapy and psy-chological intervention, Control group adopted conventional therapy only ( general support therapy and drug treatment) .After treatment about six month, clinical effects were observed and compared.Results The clinical effects of treatment group was better than that of control group, there was significant difference between two groups (0.01clinical effects on Alzheimer disease dementia early mild depression, which can improve the life quality of patients, we should be promoted in clinical work.

  11. 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...

  12. 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

  13. Study on Alzheimer's disease model

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  15. 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...

  16. 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...

  17. 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...

  18. Early psychosocial intervention in Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  19. Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

    OpenAIRE

    Wilcock, Donna M

    2012-01-01

    Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation ...

  20. Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics.

    Science.gov (United States)

    Athanasopoulos, Dimitrios; Karagiannis, George; Tsolaki, Magda

    2016-09-01

    Alzheimer disease (AD) is a chronic neurodegenerative disease with no effective cure so far. The current review focuses on the epigenetic mechanisms of AD and how nutrition can influence the course of this disease through regulation of gene expression, according to the latest scientific findings. The search strategy was the use of scientific databases such as PubMed and Scopus in order to find relative research or review articles published in the years 2012-2015. By showing the latest data of various nutritional compounds, this study aims to stimulate the scientific community to recognize the value of nutrition in this subject. Epigenetics is becoming a very attractive subject for researchers because it can shed light on unknown aspects of complex diseases like AD. DNA methylation, histone modifications, and microRNAs are the principal epigenetic mechanisms involved in AD pathophysiology. Nutrition is an environmental factor that is related to AD through epigenetic pathways. Vitamin B-12, for instance, can alter the one-carbon metabolism and thus interfere in the DNA methylation process. The research results might seem ambiguous about the clinical role of nutrition, but there is strengthening evidence that proper nutrition can not only change epigenetic biomarker levels but also prevent the development of late-onset AD and attenuate cognition deficit. Nutrition might grow to become a preventive and even therapeutic alternative against AD, especially if combined with other antidementia interventions, brain exercise, physical training, etc. Epigenetic biomarkers can be a very helpful tool to help researchers find the exact nutrients needed to create specific remedies, and perhaps the same biomarkers can be used even in patient screening in the future. PMID:27633107

  1. Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2010-01-01

    Full Text Available Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.

  2. Treatment for Alzheimer's diseases

    Directory of Open Access Journals (Sweden)

    Nina Arkadyevna Tyuvina

    2015-01-01

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

  3. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

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

    2014-04-01

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

  4. 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

  5. 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

  6. 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 ...

  7. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  10. MRI morphometry in Alzheimer's disease.

    Science.gov (United States)

    Matsuda, Hiroshi

    2016-09-01

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

  11. 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 ...

  12. 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 ...

  13. Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Donna M. Wilcock

    2012-01-01

    Full Text Available Down syndrome (DS is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

  14. Exploring Biomarkers for Alzheimer's Disease.

    Science.gov (United States)

    Sharma, Neeti; Singh, Anshika Nikita

    2016-07-01

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

  15. 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

  16. 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...

  17. Lysosomal β-galactosidase and β-hexosaminidase activities correlate with clinical stages of dementia associated with Alzheimer's disease and type 2 diabetes mellitus.

    Science.gov (United States)

    Tiribuzi, Roberto; Orlacchio, Antonio; Crispoltoni, Lucia; Maiotti, Mariangela; Zampolini, Mauro; De Angeliz, Massimiliano; Mecocci, Patrizia; Cecchetti, Roberta; Bernardi, Giorgio; Datti, Alessandro; Martino, Sabata; Orlacchio, Aldo

    2011-01-01

    Multiple epidemiological studies have shown that individuals affected by type-2 diabetes mellitus (T2DM) carry a 2-to-5-fold higher risk of developing Alzheimer's disease (AD) when compared to non-diabetic subjects. Thus, biochemical parameters that can be easily and routinely assessed for high-confidence evaluation of diabetic conditions leading to AD (AD-T2DM) are regarded as efficient tools aimed at early diagnosis and, in turn, timely AD treatment. In this regard, the activity of lysosomal glycohydrolases may of use, in light of the implication of these enzymes in early events that underlie AD pathology and an overt correlation, in diabetes, between altered metabolic homeostasis, abnormal glycohydrolase secretion in body fluids, and occurrence of diabetic complications. Based on marked up-regulation previously shown in a peripheral, cell-based model of AD, we selected β-Galactosidase, β-Hexosaminidase, and α-Mannosidase to discriminate T2DM from AD-T2DM subjects. A screen of 109, 114, and 116 patients with T2DM, AD and AD-T2DM, respectively, was performed by testing enzyme activities in both blood plasma and peripheral blood mononuclear cells. Compared to age-matched, healthy controls (n = 122), β-Galactosidase and β-Hexosaminidase activities markedly diverged across the three groups, whereas virtually unchanged values were observed for α-Mannosidase. In particular, plasma β-Galactosidase and β-Hexosaminidase levels were higher in patients with AD-T2DM compared to those with T2DM, suggesting different mechanisms leading to enzyme secretion. Statistical analyses based on ROC curves showed that both β-Galactosidase and β-Hexosaminidase activities, either intracellular or plasma-secreted, may be used to discriminate AD patients from controls and AD-T2DM from T2DM patients.

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

    Directory of Open Access Journals (Sweden)

    Florian Amtage

    2014-06-01

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

  19. Lentivirus-expressed siRNA vectors against Alzheimer disease.

    Science.gov (United States)

    Peng, Kevin A; Masliah, Eliezer

    2010-01-01

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

  20. 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.

  1. 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

  2. 糖尿病并发阿尔茨海默病患者的临床干预措施%Clinical nursing intervention of old diabetes patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    费建惠; 任颖斌; 章秋萍; 陈斌华

    2014-01-01

    目的:研究护理干预对糖尿病并发阿尔茨海默病患者的临床意义。方法研究筛选138例患者,按随机数字表法分为干预组和对照组,干预组采用治疗辅导、饮食控制、心理辅导以及基本生活作息指导等护理干预措施来观察各项措施的疗效情况。结果在治疗半个月和1个月后,干预组的餐后2 h血糖和空腹血糖与对照组比较均明显下降,且两组间比较差异有统计学意义( t分别为-2.890,-2.971,-2.822,-2.819;P<0.05)。同时,干预组患者对护理人员的满意度比例高于对照组,差异有统计学意义(69.57%比46.38%;Z=-2.966,P<0.05)。结论护理干预对于并发阿尔茨海默病的糖尿病患者能够很好地促进其病情趋于良好转归,增加其依从性。%Objective To study the clinical significance of nursing intervention in the treatment of diabetes patients with Alzheimer disease .Methods We screened 138 patients, who were randomly divided into intervention group and control group .Therapeutic counseling , diet control , psychological counseling and basic lifestyle guidance and other nursing interventions were applied in treatment of intervention group patients . Results After half and one month of intervention , the two hours postprandial blood glucose and fasting blood glucose in the intervention group were significantly decreased , compared with the control group ( t=-2.890,-2.971, -2.822, -2.819, respectively;P<0.05).Meanwhile, the nursing satisfaction in the intervention group was significantly higher than that in the control group (69.57% vs 46.38%;Z=-2.966,P<0.05). Conclusions Nursing intervention for diabetes patients with Alzheimer disease can promote patients ’ condition and increase their compliance .

  3. 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"…

  4. 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)

  5. Proline-rich polypeptides in Alzheimer's disease and neurodegenerative disorders - Therapeutic potential or a mirage?

    NARCIS (Netherlands)

    Gladkevich, A.; Bosker, F.; Korf, J.; Yenkoyan, K.; Vahradyan, H.; Aghajanov, M.

    2007-01-01

    The development of effective and safe drugs for a growing Alzheimer disease population is an increasing need at present. Both experimental and clinical evidence support a beneficial effect of proline-rich polypeptides in a number of neurodegenerative diseases, including Alzheimer disease. Experiment

  6. 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...

  7. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Narahyana Bom de Araujo

    2011-01-01

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

  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'.

  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. 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

  12. Protein Unfolding and Alzheimer's

    Science.gov (United States)

    Cheng, Kelvin

    2012-10-01

    Early interaction events of beta-amyloid (Aβ) proteins with neurons have been associated with the pathogenesis of Alzheimer's disease. Knowledge pertaining to the role of lipid molecules, particularly cholesterol, in modulating the single Aβ interactions with neurons at the atomic length and picosecond time resolutions, remains unclear. In our research, we have used atomistic molecular dynamics simulations to explore early molecular events including protein insertion kinetics, protein unfolding, and protein-induced membrane disruption of Aβ in lipid domains that mimic the nanoscopic raft and non-raft regions of the neural membrane. In this talk, I will summarize our current work on investigating the role of cholesterol in regulating the Aβ interaction events with membranes at the molecular level. I will also explain how our results will provide new insights into understanding the pathogenesis of Alzheimer's disease associated with the Aβ proteins.

  13. 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

  14. 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

  15. Using baseline cognitive severity for enriching Alzheimer's disease clinical trials: How does Mini-Mental State Examination predict rate of change?

    Science.gov (United States)

    Kennedy, Richard E.; Cutter, Gary R.; Wang, Guoqiao; Schneider, Lon S.

    2016-01-01

    Background Post hoc analyses from clinical trials in Alzheimer’s disease suggest more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition. Methods We included 2,882 participants with mild to moderate AD in 7 studies from a meta-database. We used mixed effects models to estimate rate of decline in ADAS-cog scores among MMSE groups. Findings Baseline MMSE category was associated with baseline scores and rate of decline on the ADAS-cog, adjusting for age and education (both p<0.001). Greater baseline cognitive impairment was associated with more rapid progression. Interpretations Although we found significant differences in rate of decline, the majority of differences between individuals were from baseline ADAS-cog values. Enrichment based on MMSE would reduce the recruitment pool while adding only slightly to detecting differences in rate of progression and is not advised.

  16. 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

  17. MRI Images Thresholding for Alzheimer Detection

    Directory of Open Access Journals (Sweden)

    Ali El-Zaart

    2013-05-01

    Full Text Available More than 55 illnesses are associated with the deve lopment of dementia and Alzheimer's disease (AD is the most prevalent form. Vascular dementia (VD is the second most common form of dementia. Current diagnosis of Alzheimer disease (A lzheimer's disease is made by clinical, neuropsychological, and neuroimaging assessments. M agnetic resonance imaging (MRI can be considered the preferred neuroimaging examination f or Alzheimer disease because it allows for accurate measurement of brain structures, especiall y the size of the hippocampus and related regions. Image processing techniques has been used for processing the (MRI image. Image thresholding is an important concept, both in the a rea of objects segmentation and recognition. It has been widely used due to the simplicity of im plementation and speed of time execution. Many thresholding techniques have been proposed in the literature. The aim of this paper is to provide formula and their implementation to thresho ld images using Between-Class Variance with a Mixture of Gamma Distributions. The algorith ms will be described by given their steps, and applications. Experimental results are presente d to show good results on segmentation of (MRI image.

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

    Science.gov (United States)

    Stallings, Tiffany L

    2008-06-01

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

  19. 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.

  20. Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

    Full Text Available Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine. Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine, parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF, mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  2. 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

  3. 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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  5. 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…

  6. 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.

  7. 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...

  8. 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.

  9. 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 ...

  10. 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 ...

  11. Dantrolene, a treatment for Alzheimer disease?

    Science.gov (United States)

    Liang, Li; Wei, Huafeng

    2015-01-01

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

  12. [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

  13. 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

  14. Exosomes in Alzheimer's disease.

    Science.gov (United States)

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

    2016-07-01

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

  15. 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

  16. Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease.

    Science.gov (United States)

    Venigalla, Madhuri; Gyengesi, Erika; Münch, Gerald

    2015-08-01

    Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible.

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  19. The burden of Alzheimer's disease.

    Science.gov (United States)

    Burns, Alistair

    2000-07-01

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

  20. 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 ...

  1. Huntington disease and Huntington disease-like in a case series from Brazil.

    Science.gov (United States)

    Castilhos, R M; Souza, A F D; Furtado, G V; Gheno, T C; Silva, A L; Vargas, F R; Lima, M-A F D; Barsottini, O; Pedroso, J L; Godeiro, C; Salarini, D; Pereira, E T; Lin, K; Toralles, M-B; Saute, J A M; Rieder, C R; Quintas, M; Sequeiros, J; Alonso, I; Saraiva-Pereira, M L; Jardim, L B

    2014-10-01

    The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...... heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected...

  3. [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

  4. 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...

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

    Science.gov (United States)

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

    2015-11-01

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

  6. 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

  7. 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.

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

    Science.gov (United States)

    Galimberti, Daniela; Ghezzi, Laura; Scarpini, Elio

    2013-10-15

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

  9. 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.

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. Alzheimer's Disease - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

  14. Alzheimer's May Hamper Ability to Perceive Pain

    Science.gov (United States)

    ... Alzheimer's disease required higher temperatures to report sensing warmth, mild pain and moderate pain than the other ... release. More studies are needed to explore pain perception among those with Alzheimer's disease, the researchers said. ...

  15. 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 ...

  16. 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 ...

  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. 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...

  19. Imaging markers for Alzheimer disease

    Science.gov (United States)

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

    2013-01-01

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

  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. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative co

  3. Microwaves and Alzheimer's disease

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Leroux, Charles

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

  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. 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)

  7. 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

  8. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza

    2014-03-01

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

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Tobinick Edward L

    2008-01-01

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

  11. 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

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

    Science.gov (United States)

    Bush, Ashley I; Tanzi, Rudolph E

    2008-07-01

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

  13. 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

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  16. Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes

    Science.gov (United States)

    Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Blacker, Deborah; Gómez-lsla, Teresa; Betensky, Rebecca A.; Growdon, John H.; Johnson, Keith; Frosch, Matthew P.; Sperling, Reisa A.; Hyman, Bradley T.

    2014-01-01

    Recently, ∼16% of participants in an anti-Aβ passive immunotherapy trial for mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron emission tomography (PET) scan. Whether they have AD or are AD clinical phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's Coordinating Center autopsy database and found that ∼14% of autopsied subjects clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan. More than half of these “Aβ-negative” subjects have low neurofibrillary tangle Braak stages. These findings support the implementation of a positive amyloid biomarker as an inclusion criterion in future anti-Aβ drug trials. PMID:24585367

  17. 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

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

    OpenAIRE

    Tobinick Edward L; Gross Hyman

    2008-01-01

    Abstract Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligo...

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

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

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

  20. La neuroimagen en la enfermedad de Alzheimer: perspectiva actual

    OpenAIRE

    Masdeu, J. (José)

    2004-01-01

    Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we ...

  1. 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

  2. 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)

  3. 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

  4. 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......'s disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense...

  5. Chemokines in CSF of Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2011-06-01

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

  6. 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)

  7. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

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

    2013-01-01

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

  8. Alzheimer disease and pre-emptive suicide.

    Science.gov (United States)

    Davis, Dena S

    2014-08-01

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

  9. 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

  10. 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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

    Wu, William; Small, Scott A

    2006-12-01

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

  13. 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

  14. 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.

  15. 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

  16. The neurologic examination in patients with probable Alzheimer's disease.

    Science.gov (United States)

    Huff, F J; Boller, F; Lucchelli, F; Querriera, R; Beyer, J; Belle, S

    1987-09-01

    Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.

  17. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Khairallah, M I; Kassem, L A; Yassin, N A; El Din, M A Gamal; Zekri, M; Attia, M

    2014-01-01

    Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's disease.

  18. 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

  19. 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

  20. 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)

  1. Structural connectivity of the default mode network and cognition in Alzheimer׳s disease.

    Science.gov (United States)

    Weiler, Marina; de Campos, Brunno Machado; Nogueira, Mateus Henrique; Pereira Damasceno, Benito; Cendes, Fernando; Balthazar, Marcio L F

    2014-07-30

    Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer׳s disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network.

  2. Microglia in Alzheimer Brain: A Neuropathological Perspective

    Directory of Open Access Journals (Sweden)

    Robert E. Mrak

    2012-01-01

    Full Text Available Microglia have long been noted to be present and activated in Alzheimer brain. Demonstrations that these microglia are associated with the specific lesions of Alzheimer disease—Aβ plaques and neurofibrillary tangles—and that these microglia overexpress the potent proinflammatory cytokine interleukin-1 led to the recognition of a potential pathogenic role for these cells in initiation and progression of disease. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early (diffuse and mid (neuritic stages of progression in Alzheimer brain, and only decline in end-stage, dense core plaques. They correlate with plaque distribution across cerebral cortical cytoarchitectonic layers and across brain regions. They also show close associations with tangle-bearing neurons in Alzheimer brain. Microglial activation is a consistent feature in conditions that confer increased risk for Alzheimer disease or that are associated with accelerated appearance of Alzheimer-type neuropathological changes. These include normal ageing, head injury, diabetes, heart disease, and chronic intractable epilepsy. The neuropathological demonstration of microglial activation in Alzheimer brain and in Alzheimer-related conditions opened the field of basic and applied investigations centered on the idea of a pathogenically important neuroinflammatory process in Alzheimer disease.

  3. Recent progress of PET in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Na NIU

    2014-03-01

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

  4. Alzheimer's Disease and Vitamin E

    OpenAIRE

    Empey, Matthew

    1998-01-01

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

  5. 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.

  6. 中医药治疗老年痴呆症的疗效与安全性%Clinical efficacy and safety of oral Chinese herbal medicine for Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    曾令烽; 陈云波; 王宁生; 王奇; 宓穗卿; 梁兆晖; 蔡浩斌; 孔令朔; 赵路光; 张越

    2015-01-01

    Objective To systematically evaluate efficacy and adverse events of Chinese herbal medicine( CHM) for the treatment of Alzheimer's Disease(AD).Methods Randomized controlled trial(RCTs) involving CHM or integrative medicine comparing with routine pharmacotherapy for AD were retrieved and collected from database of VIP,WANFANG,CNKI,CBM,PubMed,EMbase,and the Cochrane Li-brary.The journals related to the research were also manually searched from college library.The quality of literature was conducted by the risk of bias and quality evaluation based on the Cochrane Handbook 5.1,while the data analysis was handled by the software RevMan 5.2.6 of Cochrane Collaboration.The evidence quality grading evaluation for the system review was operated by the software of 'GRADE profiler'. Results Thirty-one studies involving 2 583 participants were contained in the meta-analysis.The main meta-analysis results indicated rela-tive benefits for the effective rate in six studies( odds ratio〔 OR〕3.35,95%CI 2.17,5.17) and the cure(control) rate in six studies(OR 1.86,95%CI 1.31,2.63) in favor of the CHM plus routine pharmacotherapy group.For CHM compared with routine pharmacotherapy,no significant difference was revealed in effective rate(OR 1.20,95%CI 0.95,1.51),cure rate(OR 1.17,95%CI 0.94,1.46) and the detailed sub-group of MMSE score at the timing-point of week-4〔weighted mean difference(WMD) 0.31,95%CI -0.38,0.99〕,week-6(WMD 0.18,95%CI-0.52,0.89),week-8(WMD 0.75,95%CI-0.32,1.83),week-12(WMD 0.06,95%CI-0.76,0.88).The GRADE quality level of this systematic review indicated"very low".Compared to the routine pharmacotherapy group(9.61%) ,the incidence of adverse e-vents of CHM(1.18%) was much lower.Conclusions As a relative safe intervention method for AD,CHM shows benefits with few adverse reactions and relative better effect of improving cognitive function incorporated with the routine pharmacotherapy;CHM reveales no statistical difference while in contrast with routine

  7. 从心肾论治阿尔茨海默病的临床效果%Clinical effect in treatment of Alzheimer disease based on the conditions of heart and kidney

    Institute of Scientific and Technical Information of China (English)

    林水淼; 王健; 周如倩; 郁志华

    2006-01-01

    疗前有显著性提高(P<0.05).结论:调心方、补肾方、多奈哌齐均能改善阿尔茨海默病患者的认知功能和日常生活能力,调心方、补肾方是治疗阿尔茨海默病有效的中药制剂.%BACKGROUND: Clinically Alzheimer disease (AD) is characterized by obscurity in onset, decline of intelligence, and dysfunctions of behavior and nerve system. The essence of AD is impairment of memory and cognition.OBJECTIVE: To explore the effective mechanism of tiaoxin recipe (TXR)and bushen recipe (BSR) in treating AD.DESIGN: Randomized controlled study.SETTING: Shanghai Institute of Traditional Chinese Medicine for Geriatrics.PARTICIPANTS: Totally 60 AD patients were selected from Shanghai Institute of Traditional Chinese Medicine for Geriatrics from October 1999to January 2000.METHODS: Sixty patients with AD were divided into 3 groups, with 20in each group. The patients in TXR and BSR group took respectively TXR and BSR 10 mL once, 2 times per day. The patients in donepezil (Dp)group took a Dp capsule once a day, h.s (Dp was produced in England Boots Company, 5 mg per capsule). For a course consisted of 12 weeks.The changes of Mini mental state examination (MMSE) score, Activity of Daily Living Scale (ADL) score, neuropsychological testing (NPT) score,including FULD object-memory evaluation (FOM), rapid verbal retrieval (RVR), digit span test (DS) and block design (BD), as well as the overall operational evaluation before and after treatment were analyzed.MAIN OUTCOME MEASURES: Scores of MMSE, ADL, NPT and the overall operational evaluation.RESULTS: Totally 60 patients entered the final analysis. ① MMSE scores in the 3 groups were decreased after treatment as compared with those before treatment (P < 0.01). Total effective rates were 70%, 65% and 75% respectively (P > 0.05). ② ADL scores in the 3 groups were decreased after treatment as compared with those before treatment (P < 0.05or P < 0.01). Total effective rates were 45%, 45% and 40% respectively (P > 0

  8. 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

  9. Spatial Navigation in Preclinical Alzheimer's Disease

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-06-01

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

  11. Impaired default network functional connectivity in autosomal dominant Alzheimer disease

    Science.gov (United States)

    Chhatwal, Jasmeer P.; Schultz, Aaron P.; Johnson, Keith; Benzinger, Tammie L.S.; Jack, Clifford; Ances, Beau M.; Sullivan, Caroline A.; Salloway, Stephen P.; Ringman, John M.; Koeppe, Robert A.; Marcus, Daniel S.; Thompson, Paul; Saykin, Andrew J.; Correia, Stephen; Schofield, Peter R.; Rowe, Christopher C.; Fox, Nick C.; Brickman, Adam M.; Mayeux, Richard; McDade, Eric; Bateman, Randall; Fagan, Anne M.; Goate, Allison M.; Xiong, Chengjie; Buckles, Virginia D.; Morris, John C.

    2013-01-01

    Objective: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. Methods: Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). Results: We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. Conclusion: Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease. PMID:23884042

  12. 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

  13. [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.

  14. 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

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

    Science.gov (United States)

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

    2008-08-01

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

  16. 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.

  17. 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.

  18. Turning principles into practice in Alzheimer's disease

    NARCIS (Netherlands)

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

    2010-01-01

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

  19. Estrogen and early-onset Alzheimer's disease

    NARCIS (Netherlands)

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

    1999-01-01

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

  20. 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?

  1. Fatty acids, lipid metabolism and Alzheimer pathology.

    NARCIS (Netherlands)

    Hooijmans, C.R.; Kiliaan, A.J.

    2008-01-01

    Alzheimer's disease is the most common form of dementia in the elderly. The cause of Alzheimer's disease is still unknown and there is no cure for the disease yet despite 100 years of extensive research. Cardiovascular risk factors such as high serum cholesterol, presence of the Apolipoprotein epsil

  2. 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

  3. Preclinical Alzheimer disease —the challenges ahead

    Science.gov (United States)

    Sperling, Reisa A.; Karlawish, Jason; Johnson, Keith A.

    2013-01-01

    There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice. PMID:23183885

  4. 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)

  5. 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...

  6. 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.

  7. A case-control study of apolipoprotein E genotypes in Alzheimer's disease associated with Down syndrome.

    NARCIS (Netherlands)

    H.M. Evenhuis (Heleen); C.M. van Duijn (Cock); W.A. van Gool (Willem)

    1995-01-01

    textabstractThe prevalence of clinical signs and neuropathological findings of Alzheimer's disease (AD) is high in Down's syndrome (DS). In the general population, the apolipoprotein E (ApoE) epsilon 4 isoform is an important risk for AD. We studied the allelic frequencies of ApoE in 26 DS cases ful

  8. 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

  9. 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…

  10. 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.

  11. 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...

  12. 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

  13. Increased CSF alpha-synuclein levels in Alzheimer's disease : Correlation with tau levels

    NARCIS (Netherlands)

    Slaets, Sylvie; Vanmechelen, Eugeen; Le Bastard, Nathalie; Decraemer, Hilde; Vandijck, Manu; Martin, Jean-Jacques; De Deyn, Peter Paul; Engelborghs, Sebastiaan

    2014-01-01

    Background: Given the difficult clinical differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest resulted in research on alpha-synuclein as a potential cerebrospinal fluid biomarker (CSF) for synucleinopathies. Methods: CSF alpha-synuclein-140 co

  14. Optimizing the diagnosis of early Alzheimer's disease in mild cognitive impairment subjects

    DEFF Research Database (Denmark)

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

    2012-01-01

    In the diagnostic process of Alzheimer's disease (AD), there may be considerable delays between first contact to outpatient services and a final, definitive diagnosis. In Europe the average delay is 20 months. Nevertheless, patient data preceding clinical AD diagnoses often contains early signs...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  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. 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...... index, 0.87, and correlation coefficient, 0.94, with semi-automatically generated segmentations. When comparing hippocampus volumes extracted from 1.5T and 3T images, the absolute value of the difference was low: 3.2% of the volume. The correct classification rate for Alzheimer's disease and cognitively...

  18. [BACE1 inhibitors for the treatment of Alzheimer disease].

    Science.gov (United States)

    Tomita, Taisuke

    2016-03-01

    β-Site amyloid precursor protein cleaving enzyme 1 (BACEl) is the enzyme required for the production of the amyloid-β peptide(Aβ), which is associated with Alzheimer disease (AD). BACEl has emerged as a prime molecular target for reducing the brain Aβ levels. Recently, several BACEl inhibitors have been developed in clinical trials to test the efficacy in AD patients and individuals with prodromal AD. However, identification of BACE1 substrates and phenotypes of Bace1 knockout mice have raised concerns regarding potential mechanism-based adverse effects. This review summarizes the current status of the development of BACE1 inhibitors and the evaluation of their therapeutic potential against AD.

  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. 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

  1. The "Alzheimer's disease signature": potential perspectives for novel biomarkers

    Directory of Open Access Journals (Sweden)

    Zella Davide

    2011-09-01

    Full Text Available Abstract Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis.

  2. 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.

  3. 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

  4. 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

  5. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    Energy Technology Data Exchange (ETDEWEB)

    Poduslo, S.E. [Texas Tech Univ., Lubbock, TX (United States); Schwankhaus, J.D. [Department of Veterans Affairs, Lubbock, TX (United States)

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  6. Does insulin therapy for type 1 diabetes mellitus protect against Alzheimer's disease?

    Science.gov (United States)

    Rdzak, Grzegorz M; Abdelghany, Osama

    2014-12-01

    Alzheimer's disease is the most common cause of dementia in the United States. A better understanding of the disease's underlying pathways may provide novel treatment and/or prevention strategies for this progressive chronic neurodegenerative disorder. In recent years, there has been a growing interest in the possible links between insulin and Alzheimer's disease. Insulin-induced hypoglycemia causes adaptive changes in the brain, including an improved ability to use alternative fuels. Insulin has been shown to facilitate reduction of intracellular amyloid plaque and downregulation of amyloid-β-derived diffusible ligand-binding sites. Insulin also promotes tau hypophosphorylation, which stabilizes microtubules and promotes tubulin polymerization. Excess exogenous insulin may also play a role in overcoming the decreased utilization and transport of glucose in patients with Alzheimer's disease. Intranasal insulin therapy may have beneficial effects on cognition and function in patients with Alzheimer's disease, as well as having only minor adverse effects, and this route of administration been the focus in clinical trials. These data support the mechanistic pathways that might link excess exogenous insulin administered to patients with type 1 diabetes mellitus to possible protection from Alzheimer's disease and provide a rationale for using insulin to prevent the disease in high-risk patients.

  7. A test of lens opacity as an indicator of preclinical Alzheimer Disease.

    Science.gov (United States)

    Bei, Ling; Shui, Ying-Bo; Bai, Fang; Nelson, Suzanne K; Van Stavern, Gregory P; Beebe, David C

    2015-11-01

    Previous studies reported that characteristic lens opacities were present in Alzheimer Disease (AD) patients postmortem. We therefore determined whether cataract grade or lens opacity is related to the risk of Alzheimer dementia in participants who have biomarkers that predict a high risk of developing the disease. AD biomarker status was determined by positron emission tomography-Pittsburgh compound B (PET-PiB) imaging and cerebrospinal fluid (CSF) levels of Aβ42. Cognitively normal participants with a clinical dementia rating of zero (CDR = 0; N = 40) or with slight evidence of dementia (CDR = 0.5; N = 2) were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimer's Disease Research Center. The age, sex, race, cataract type and cataract grade of all participants were recorded and an objective measure of lens light scattering was obtained for each eye using a Scheimpflug camera. Twenty-seven participants had no biomarkers of Alzheimer dementia and were CDR = 0. Fifteen participants had biomarkers indicating increased risk of AD, two of which were CDR = 0.5. Participants who were biomarker positive were older than those who were biomarker negative. Biomarker positive participants had more advanced cataracts and increased cortical light scattering, none of which reached statistical significance after adjustment for age. We conclude that cataract grade or lens opacity is unlikely to provide a non-invasive measure of the risk of developing Alzheimer dementia.

  8. 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.

  9. 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

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

    Science.gov (United States)

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

    2015-07-01

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

  11. 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

  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. 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.

  14. 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...

  15. 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...

  16. 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

  17. Lithium May Fend off Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 夏红

    2004-01-01

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

  18. Alzheimer's 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 ...

  19. 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. ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  4. Circulating Biomarker Panels in Alzheimer's Disease.

    Science.gov (United States)

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

    2015-01-01

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

  5. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

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

    2012-01-01

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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. The economic costs of Alzheimer's disease.

    Science.gov (United States)

    Hay, J W; Ernst, R L

    1987-09-01

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

  11. 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

  12. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies.

    Science.gov (United States)

    Ringman, John M; Goate, Alison; Masters, Colin L; Cairns, Nigel J; Danek, Adrian; Graff-Radford, Neill; Ghetti, Bernardino; Morris, John C

    2014-11-01

    Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer's disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses.

  13. 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.

  14. Investigating interventions in Alzheimer's disease with computer simulation models.

    Directory of Open Access Journals (Sweden)

    Carole J Proctor

    Full Text Available Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Tjaard U. Hoogenraad

    2011-01-01

    Full Text Available 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. There are 2 neurodegenerative diseases with abnormalities in copper metabolism: (a the juvenile form with degeneration in the basal ganglia (Wilson's disease and (b the age related form with cortical neurodegeneration (Alzheimer's disease. Initially the hypothesis has been that neurodegeneration was caused by accumulation of copper in the brain but later experiences with treatment of Wilson's disease led to the conviction that free plasma copper is the toxic form of copper: it catalyzes amyloid formation thereby generating oxidative stress, free radicals and degeneration of cortical neurons. Hypothesis 2: Oral zinc therapy is an effective and safe treatment of free copper toxicosis in Alzheimer's disease. Proposed dosage: 50 mg elementary zinc/day. Warning: Chelation therapy is irrational and dangerous in treatment of copper toxicosis in Alzheimer's disease.

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

    Science.gov (United States)

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

    2012-07-01

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

  19. Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Luciane F. Viola

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatry symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing, physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield

  20. 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

  1. 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

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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 ...

  6. 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

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. Could Loneliness Be an Early Sign of Alzheimer's?

    Science.gov (United States)

    ... html Could Loneliness Be an Early Sign of Alzheimer's? People with 'biomarkers' for the brain disease were ... Subtle feelings of loneliness might warn of impending Alzheimer's disease in older folks, a new study suggests. ...

  13. 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 ...

  14. 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) ...

  15. 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...

  16. 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

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

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    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

  18. Alzheimer's disease is incurable but preventable.

    Science.gov (United States)

    de la Torre, Jack C

    2010-01-01

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

  19. 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

  20. 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)

  1. Biomedicine and Informatics Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Kang Cheng

    2007-01-01

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

  2. The Search for Biomarkers in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-04-01

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

  3. Suspected non-Alzheimer disease pathophysiology—concept and controversy

    Science.gov (United States)

    Jack, Clifford R.; Knopman, David S.; Chételat, Gaël; Dickson, Dennis; Fagan, Anne M.; Frisoni, Giovanni B.; Jagust, William; Mormino, Elizabeth C.; Petersen, Ronald C.; Sperling, Reisa A.; van der Flier, Wiesje M.; Villemagne, Victor L.; Visser, Pieter J.; Vos, Stephanie J. B.

    2016-01-01

    Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to individuals who are clinically normal for their age and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be confidently inferred from the clinical presentation. SNAP is present in ~23% of clinically normal individuals aged >65 years and in ~25% of mildly cognitively impaired individuals. APOE4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-β biomarkers. In this Perspectives article we describe the available data on SNAP and address topical controversies in the field. PMID:26782335

  4. 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

  5. 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.

  6. 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

  7. An anemia of Alzheimer's disease.

    Science.gov (United States)

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

    2014-11-01

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

  8. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

    Science.gov (United States)

    2011-11-04

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

  9. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012

    Science.gov (United States)

    2012-11-06

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

  10. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

    Science.gov (United States)

    2013-11-05

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

  11. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010

    Science.gov (United States)

    2010-11-04

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

  12. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

    Science.gov (United States)

    2012-02-24

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

  13. 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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Catricala Silvia

    2012-09-01

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

  16. 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.

  17. 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.

  18. 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.)

  19. 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

  20. 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

  1. Rate of Conversion from Prodromal Alzheimer's Disease to Alzheimer's Dementia: A Systematic Review of the Literature

    Directory of Open Access Journals (Sweden)

    Alex Ward

    2013-09-01

    Full Text Available Background: The purpose of this study was to summarize published estimates for conversion from mild cognitive impairment or amnestic mild cognitive impairment to Alzheimer's dementia. We carried out a systematic review of English language publications to identify cohort studies published since January 2006 that reported the risk or rate of conversion. Summary: Thirty-two cohort studies were identified, of which 14 reported annualized conversion rates (ACRs. Conversions over 1 year ranged from 10.2 to 33.6% (5 studies, median: 19.0%, and over 2 years from 9.8 to 36.3% (7 studies, median: 18.6%. ACRs ranged from 7.5 to 16.5% (7 studies, median: 11.0% per person-year for studies recruiting from clinics, and from 5.4 to 11.5% (7 studies, median: 7.1% for community samples. Key Message: Extensive variation was observed in conversion rates due to the population sampled, diagnostic criteria, and duration, and because many studies did not account for loss to follow-up.

  2. 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

  3. 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.

  4. 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

  5. The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer's pathology in animal models of Alzheimer's disease: a systematic review and meta-analysis.

    NARCIS (Netherlands)

    Hooijmans, C.R.; Pasker-de Jong, P.C.M.; Vries, R.B.M. de; Ritskes-Hoitinga, M.

    2012-01-01

    To date, only a few randomized clinical trials (RCTs) have investigated the effects of omega-3 fatty acids (FA) on Alzheimer's disease (AD). Some of these studies demonstrated that patients with very mild AD or mild cognitive impairment benefit from omega-3 FA treatment, but none showed significant

  6. 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.

  7. Diagnosis of Alzheimer's disease with [18F]PET in mild and asymptomatic stages.

    Science.gov (United States)

    Drzezga, Alexander

    2009-01-01

    With longer life expectancy, dementia based on the age-related Alzheimers' disease (AD) has turned into one of the most prevalent disorders of older age, representing a serious medical and socio-economic issue. There has been growing interest in early diagnosis of this disease, particularly regarding the initiation of new treatment strategies ahead of the onset of irreversible neuronal damage. It is accepted that the pathologic changes underlying AD appear in the brain years to decades before the symptomatic stages. Consequently, clinical measures of cognitive impairment, as used for definition of dementia, will not allow early diagnosis of AD-pathology in the mild or asymptomatic stages. Thus, a need for complementary sensitive biomarkers is apparent. Brain imaging markers are among the most promising candidates for this diagnostic challenge. Particularly, [18F]FDG PET as a marker of regional neuronal function has been demonstrated to represent a most sensitive and specific method for early identification of AD-pathology and thus for prediction of dementia of the Alzheimer type (DAT), even in the mild and asymptomatic stages. Currently, systematic data of comparable quality are hardly available for any other imaging procedure. The purpose of this article is to describe the typical findings of [18F]FDG PET in different stages of AD and to demonstrate its value for early and reliable diagnosis of Alzheimer's disease, particularly ahead of the stage of dementia of the Alzheimer's type.

  8. Alois Alzheimer and Gaetano Perusini: Should Man Divide What Fate United?

    Directory of Open Access Journals (Sweden)

    G. Macchi

    1997-01-01

    Full Text Available Three points of interest lie in considering how Alzheimer, and more significantly Perusini, struggled to throw light on the cause of this devastating disease. There is a stimulating possibility that Perusini believed presenile forms of Alzheimer’s disease described the same disease as senile forms. If so this would anticipate current opinion, and reveal Perusini to dissent from Kraepelin. In addition, Perusini may have understood the pathological relationship between neuritic plaques and vascular changes, once more foreseeing the modern view of Alzheimer’s disease. Finally, Perusini and Alzheimer disagreed with Jung's view concerning the relationship between neuropathology and clinical psychiatry. This point highlights the major change occurring at that time from classical neurology to the psychoanalytic era. In his last work (1911 Alzheimer quoted his Italian disciple many times, even speaking of ‘Perusini's cases’ (Perusinischen Fälle. This article is an attempt to change the eponym of Alzheimer’s disease into the Alzheimer-Perusini disease. This is a brief history of a master and his disciple, whose scientific lives were, by events, divided.

  9. 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

  10. Towards the Neuropsychological Diagnosis of Alzheimer's Disease: A Hybrid Model in Decision Making

    Science.gov (United States)

    de Castro, Ana Karoline Araujo; Pinheiro, Placido Rogerio; Pinheiro, Mirian Caliope Dantas

    Dementias are syndromes described by a decline in memory and other neuropsychological changes especially occurring in the elderly and increasing exponentially in function of age. Due to this fact and the therapeutical limitations in the most advanced stage of the disease, diagnosis of Alzheimer's disease is extremely important and it can provide better life conditions to patients and their families. This work presents a hybrid model, combining Influence Diagrams and the Multicriteria Method, for aiding to discover, from a battery of tests, which are the most attractive questions, in relation to the stages of CDR (Clinical Dementia Rating) in decision making for the diagnosis of Alzheimer's disease. This disease is the most common dementia. Influence Diagram is implemented using GeNie tool. Next, the judgment matrixes are constructed to obtain cardinal value scales which are implemented through MACBETH Multicriteria Methodology. The modeling and evaluation processes were carried out through a battery of standardized assessments for the evaluation of cases with Alzheimer's disease developed by Consortium to Establish a Registry for Alzheimer's disease (CERAD).

  11. Stem cell treatment for Alzheimer's disease.

    Science.gov (United States)

    Li, Ming; Guo, Kequan; Ikehara, Susumu

    2014-10-23

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

  12. Clinical analysis of behavioral and psychological symptoms in Alzheimer's disease and vascular dementia%老年性阿尔茨海默病与血管性痴呆患者的行为和精神症状的比较

    Institute of Scientific and Technical Information of China (English)

    杜俊秋; 杨清泉; 孙晖; 王永香; 杨林; 韩明

    2016-01-01

    Objective To investigate behavioral and psychological symptoms in elderly patients with dementia.Methods 80 elderly patients with dementia were selected in hospital from May 2011 to May 2015.40 patients were vascular dementia as control group .40 patients were Alzheimer's disease as observation group .Patients were assessed by scale of behavioral pathology in Alzheimer 's disease ( Behave-AD).Behavioral and psychological symptoms were compared between two groups .Results Incidence of paranoia and delusions ; incidence of behavior disorders; incidence of aggressive behavior ; incidence of anxiety and fear in observation group were significantly higher than control group.Paranoia and delusions score ; behavior disorder score; aggressive behavior score; anxiety and fear score in observation group were significantly higher than control group .Differences were statistically significant(P0.05).Conclusion Incidence of behavioral and psychological symptoms is higher in elderly patients with dementia .Clinical manifestations of dementia patients in different types are different , which should pay close attention .%目的:探讨阿尔茨海默病痴呆患者的行为和精神症状。方法选取本院2011年5月至2015年5月诊治的痴呆性老年患者80例,其中血管性痴呆(VD)患者40例为 VD 组,阿尔茨海默病(AD)患者40例为 AD 组,均行 AD 行为评分表(Behave-AD)评定,比较两组患者的行为和精神症状。结果AD 组患者偏执和妄想发生率、行为紊乱发生率、攻击行为发生率、焦虑和恐惧发生率均明显高于 VD 组,AD 组患者偏执和妄想评分、行为紊乱评分、攻击行为评分、焦虑和恐惧评分、总评分均明显高于 VD 组,差异有统计学意义(P<0.05)。 AD 组患者幻觉发生率高于 VD 组,AD 组患者日间节律紊乱发生率、情感障碍发生率均低于 VD组,AD 组患者幻觉评分高于 VD 组,AD 组患者日间节律紊乱评分

  13. Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid beta42.

    NARCIS (Netherlands)

    Mattsson, N.; Zegers, I.; Andreasson, U.; Bjerke, M.; Blankenstein, M.A.; Bowser, R.; Carrillo, M.C.; Gobom, J.; Heath, T.; Jenkins, R.; Jeromin, A.; Kaplow, J.; Kidd, D.; Laterza, O.F.; Lockhart, A.; Lunn, M.P.; Martone, R.L.; Mills, K.; Pannee, J.; Ratcliffe, M.; Shaw, L.M.; Simon, A.J.; Soares, H.; Teunissen, C.E.; Verbeek, M.M.; Umek, R.M.; Vanderstichele, H.; Zetterberg, H.; Blennow, K.; Portelius, E.

    2012-01-01

    Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concen

  14. 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

  15. 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

  16. Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer's disease: A systematic review of randomized controlled trials

    NARCIS (Netherlands)

    Rijpma, A; Meulenbroek, O.V.; Olde Rikkert, M.G.M.

    2014-01-01

    To date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may alleviate symptoms and alter the disease course in a synergistic manner. This systematic review examines the effect of adding nutritional

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  2. 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.

  3. Latino Alzheimer's disease caregivers and depression: using the stress coping model to examine the effects of spirituality and religion.

    Science.gov (United States)

    Sun, Fei; Hodge, David R

    2014-04-01

    This study used stress coping theory to examine the effects of spirituality and religion on depression among a sample of Latino family members caring for a person with Alzheimer's disease (AD) in the United States. Participants consisted of 209 Latino caregivers (CGs) drawn from baseline data from the Resource for Enhancing Alzheimer's Caregivers Health (REACH) II clinical trial. The findings indicate that church attendance moderates the relationship between subjective forms of stress and depression in tandem with exhibiting direct effects on depression. Consistent with the central role religion plays in Latino culture, the results imply that religious involvement may play an important role in mitigating depression through indirect and direct pathways.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  6. A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomized Danish Alzheimer Intervention Study (DAISY)

    DEFF Research Database (Denmark)

    Phung, K.T.T.; Waldorff, F.B.; Buss, D.V.;

    2013-01-01

    OBJECTIVES: To examine the long-term efficacy at the 36-month follow-up of an early psychosocial counselling and support programme lasting 8-12 months for community-dwelling patients with mild Alzheimer's disease and their caregivers. DESIGN: Multicentre, randomised, controlled, rater-blinded trial....... SETTING: Primary care and memory clinics in five Danish districts. PARTICIPANTS: 330 home-dwelling patients with mild Alzheimer's disease and their primary caregivers (dyads). INTERVENTIONS: Dyads were randomised to receive intervention during the first year after diagnosis. Both intervention and control...... of Life Scale for Alzheimer's disease (QoL-AD), Neuropsychiatric Inventory-Questionnaire, Alzheimer's disease Cooperative Study Activities of Daily Living Scale, all-cause mortality and nursing home placement. RESULTS: At a 36-month follow-up, 2 years after the completion of the Danish Alzheimer...

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

    Science.gov (United States)

    Demetrius, Lloyd A; Magistretti, Pierre J; Pellerin, Luc

    2014-01-01

    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. PMID:25642192

  8. Epidemiologia e riabilitazione della malattia di Alzheimer: un approccio psicosociale

    Directory of Open Access Journals (Sweden)

    Pasquale Scarnera

    2015-08-01

    Full Text Available Epidemiology and Rehabilitation of Alzheimer’s Disease: A Psychosocial Approach - The improvement of the welfare conditions that has characterized the high-income societies after the II World War and the increase in brain and cognitive resources through which people face aging, could mitigate in the future the incidence of dementia and Alzheimer's disease, the prevalent among all dementias. Nevertheless, the estimations of prevalence and incidence of this disease still acknowledge about dramatic decline especially regarding the relationship between the number of people affected and the number of healthy people able to care for them as informal caregivers. The aptitude to address these changes through health / social services is limited by the lack of effective models of interventions. The research in the psychosocial field oriented to the integrated assessment of personality suggests interesting perspectives in the preventive, clinical and rehabilitation care.

  9. Multitarget drugs of plants origin acting on Alzheimer's disease.

    Science.gov (United States)

    Russo, P; Frustaci, A; Del Bufalo, A; Fini, M; Cesario, A

    2013-01-01

    The etiopathology of Alzheimer's disease (AD) is extremely complex and heterogeneous, often associated with comorbidities. As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target. The current tendency in drug design and discovery in AD is the rational design or "serendipitous" discovery of new drug entities challenging multiple targets. Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs. Multifunctional drugs often have their origin in natural sources. This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD. PMID:23410167

  10. [Molecular imaging for early diagnosis of Alzheimer's disease].

    Science.gov (United States)

    Pozo García, Miguel Angel

    2004-01-01

    The progressive aging of the population and the difficulty of diagnosing and treating Alzheimer's disease (AD) portends an exponencial increase in the prevalence of this illness. One way to approach this social and health problem is to develop diagnostic techniques that allow us to detect the disease in its pre-clinical stages and apply early treatment that can slow down AD advance. Molecular imaging, in particular that generated by positron emission tomography with 2-fluoro-2 deoxi-D-glucose (PET-FDG) has shown high sensitivity in detecting changes in cerebral metabolic activity in the early stages of AD, and allow other dementias and physiological changes that accompany normal aging to be distinguished from AD. PMID:15997594

  11. Neuropeptides in Alzheimer's disease: from pathophysiological mechanisms to therapeutic opportunities.

    Science.gov (United States)

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

    2013-06-01

    Neuropeptides are found throughout the entire nervous system where they can act as neurotransmitter, neuromodulator or neurohormone. In those functions, they play important roles in the regulation of cognition and behavior. In brain disorders like Alzheimer's disease (AD), where abnormal cognition and behavior are observed, the study of neuropeptides is particularly interesting since altered neuropeptides can function as biomarkers or as targets for new medication. In this article neuropeptides with relevance to AD are listed and their influence on cognitive and behavioral disturbances is discussed. Findings from human cerebrospinal fluid and brain tissue, and AD mouse models are described and related to the pathophysiology and symptomatology of the disease. In the past, clinical trials with neuropeptides have often failed due to insufficient delivery to the brain. Therefore, new strategies to target the brain with peptide drugs are also covered.

  12. Swallowing in moderate and severe phases of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Sheilla de Medeiros Correia

    2010-12-01

    Full Text Available OBJECTIVE: To characterize the problems of feeding and swallowing in individuals with moderate and severe Alzheimer´s disease (AD and to correlate these with functional aspects. METHOD: Fifty patients with AD and their caregivers participated in this study. The instruments used were: Clinical Dementia Rating (CDR, Mini-Mental State Examination, Index of Activities of Daily Living, Assessment of Feeding and Swallowing Difficulties in Dementia, Functional Outcome Questionnaire for Aphasia, and Swallowing Rating Scale. RESULTS: Problems with passivity, distraction and refusal to eat were encountered in the CDR2 group. Distraction, passivity and inappropriate feeding velocity were predominant in the CDR3 group. The problems were correlated with communication, swallowing severity of AD individuals and caregiver schooling. CONCLUSION: Given the inexorable functional alterations during the course of the disease, it is vital to observe these in patients with a compromised feeding and swallowing mechanism. The present study supplies the instruments to orient caregivers and professionals.

  13. Targeting microglia for the treatment of Alzheimer's Disease.

    Science.gov (United States)

    Wes, Paul D; Sayed, Faten A; Bard, Frédérique; Gan, Li

    2016-10-01

    While histological changes in microglia have long been recognized as a pathological feature of Alzheimer's disease (AD), recent genetic association studies have also strongly implicated microglia in the etiology of the disease. Coding and noncoding polymorphisms in several genes expressed in microglia-including APOE, TREM2, CD33, GRN, and IL1RAP-alter AD risk, and therefore could be considered as entry points for therapeutic intervention. Furthermore, microglia may have a substantial effect on current amyloid β (Aβ) and tau immunotherapy approaches, since they are the primary cell type in the brain to mediate Fc receptor-facilitated antibody effector function. In this review, we discuss the considerations in selecting microglial therapeutic targets from the perspective of drug discovery feasibility, and consider the role of microglia in ongoing immunotherapy clinical strategies. GLIA 2016;64:1710-1732. PMID:27100611

  14. Alzheimer's disease: a mathematical model for onset and progression

    CERN Document Server

    Bertsch, Michiel; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2015-01-01

    In this paper we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium, and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Even though we deliberately neglect many aspects of the complexity of the brain and the disease, numerical simulations are in good qualitative agreement with clinical...

  15. S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.

    Science.gov (United States)

    Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B; Ravindra, Kodihalli C; Wishnok, John S; Tsai, Li-Huei; Tannenbaum, Steven R

    2016-04-12

    Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein's function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25-inducible mouse model of Alzheimer's disease-like neurodegeneration. The approach-SNOTRAP (SNO trapping by triaryl phosphine)-is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer's disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration.

  16. Rates of decline in Alzheimer disease decrease with age.

    Directory of Open Access Journals (Sweden)

    Dominic Holland

    Full Text Available Age is the strongest risk factor for sporadic Alzheimer disease (AD, yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI, and cognitively healthy (HC individuals aged 65 to 90 years (total n = 723. The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42, tau, and phospho-tau(181p (ptau, showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.

  17. 78 FR 46590 - Office of the Assistant Secretary for Planning and Evaluation; Advisory Council on Alzheimer's...

    Science.gov (United States)

    2013-08-01

    ... Alzheimer's Research, Care, and Services AGENCY: Office of the Assistant Secretary for Planning and... soliciting nominations for six non-Federal members of the Advisory Council on Alzheimer's Research, Care, and... Alzheimer's Project Act: Alzheimer's patient advocate, Alzheimer's caregiver, health care...

  18. Italian Verb Inflection in Alzheimer Dementia

    Science.gov (United States)

    Colombo, Lucia; Fonti, Cristina; Stracciari, Andrea

    2009-01-01

    A group of 20 patients with probable Alzheimer disease (AD) and a control group were tested in a verb generation task, in a verb synonym task and several cognitive tests. Three types of verbs and novel verbs were presented in simple sentence frames, in two different conditions. In one condition participants were presented with the verb in the…

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

    Science.gov (United States)

    Jones, Jeffrey M; Jones, Joni L

    2010-03-01

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

  20. Cannabinoids in late-onset Alzheimer's disease

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. Estrogen receptor beta treats Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  2. Atorvastatin attenuates oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Cai Zhiyou; Yan Yong; Wang Yonglong

    2008-01-01

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

  3. Alzheimer disease : presenilin springs a leak

    NARCIS (Netherlands)

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

    2006-01-01

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

  4. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

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

    2013-01-01

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

  5. Structural Neuroimaging in Aging and Alzheimer's Disease

    NARCIS (Netherlands)

    Vernooij, Meike W.; Smits, Marion

    2012-01-01

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

  6. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

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

    2013-01-01

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

  7. Early diagnosis of Alzheimer's via PET probe

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Alzheimer's disease (AD),a neurodegenerative disorder that impairs memory,cognition and behavior,has become the most frequent senile dementia,currently crippling more than 20 million people across the world.Scientists have found that the accumulation of amyloid plaques in the brain features the pathological change of the disease.

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

    NARCIS (Netherlands)

    F. van Dam; W.A. van Gool

    2009-01-01

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

  9. Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

    Science.gov (United States)

    MacDonald, Alan B

    2007-01-01

    Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through

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

    Directory of Open Access Journals (Sweden)

    Gattaz Wagner F

    2010-12-01

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

  11. Endothelial progenitor cells with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  12. Art Therapy for an Individual with Late Stage Dementia: A Clinical Case Description

    Science.gov (United States)

    Tucknott-Cohen, Tisah; Ehresman, Crystal

    2016-01-01

    This article describes the healing benefits of art therapy for an individual with dementia of the Alzheimer's type. In this clinical case description, a woman diagnosed with Alzheimer's disease received individual art therapy for 17 weeks. The treatment concerns that arose, altered view of reality, agitation, and retrogenesis provide insight on…

  13. 78 FR 36192 - Agency Information Collection Activities: Submission for OMB Review; Comment Request; Alzheimer's...

    Science.gov (United States)

    2013-06-17

    ... for OMB Review; Comment Request; Alzheimer's Disease Supportive Services Program--Data Reporting Tool... information collection requirements relating to the continuation of an existing collection for the Alzheimer's...: The Alzheimer's Disease Supportive Services Program (ADSSP) is authorized through Sections 398,...

  14. 78 FR 54254 - Agency Information Collection Activities: Submission for OMB Review; Comment Request; Alzheimer's...

    Science.gov (United States)

    2013-09-03

    ... for OMB Review; Comment Request; Alzheimer's Disease Supportive Services Program--Data Reporting Tool... collection of information for the Alzheimer's Disease Supportive Services Program. The proposed collection of....Tilly@acl.hhs.gov . SUPPLEMENTARY INFORMATION: The Alzheimer's Disease Supportive Services...

  15. 75 FR 28809 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Alzheimer's...

    Science.gov (United States)

    2010-05-24

    ... Review; Comment Request; Alzheimer's Disease Supportive Services Program Standardized Data Collection... clearance. The Alzheimer's Disease Supportive Services Program (ADSSP) is authorized through Sections 398... Care and Alzheimer's Disease Amendments of 1990. The ADSSP helps states extend supportive services...

  16. 75 FR 12241 - Agency Information Collection Activities; Proposed Collection; Comment Request; Alzheimer's...

    Science.gov (United States)

    2010-03-15

    ...; Comment Request; Alzheimer's Disease Supportive Services Program Standardized Data Collection AGENCY... notice solicits comments on the information collection requirements relating to the Alzheimer's Disease... appropriate, and other forms of information technology. The Alzheimer's Disease Supportive Services...

  17. The use of errorless learning strategies for patients with Alzheimer's disease: a literature review.

    Science.gov (United States)

    Li, Ruijie; Liu, Karen P Y

    2012-12-01

    The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included 'errorless learning or practice' and 'Alzheimer's disease'. Four studies that fulfilled the inclusion criteria were selected and reviewed. Two of the studies were clinical controlled trials: one was a single-group pretest-post-test trial and the other was a multiple single-participant study. Demographic variables, design, treatment and outcome measures were summarized. Recall trials were used as the primary outcome measure. Results indicate that the use of errorless learning promotes better retention of specific types of information. Errorless learning is effective in memory rehabilitation of older adults with Alzheimer's disease. However, it would require more studies with unified outcome measures to allow for the formulation of standardized clinical protocol and recommendations.

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

    Science.gov (United States)

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

    2016-09-01

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

  19. Effectiveness of Music Therapy in Alzheimer Patients: Systematic Review

    Directory of Open Access Journals (Sweden)

    Neslihan Lok

    Full Text Available The incidence of Alzheimers disease increases with advancing age. This increase cause significant economic and emotional burden on family and national health care system which makes Alzheimers disease a national issue to be considered. Music therapy could be an alternative treatment approach in Alzheimer's disease. Especially in the second stage of Alzheimers disease, growth and expansion of amyloid plaques results in anger and aggression among patients. Calming effects of music might be beneficial in management of patients during this period. This study is a systematic review of researches conducted to determine the effects of music therapy in Alzheimer's diseases. In sum results have supported possible positive effects of music therapy on Alzheimer patients. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(3.000: 266-274

  20. Electroencephalogram and Alzheimer's Disease: Clinical and Research Approaches

    OpenAIRE

    Anthoula Tsolaki; Dimitrios Kazis; Ioannis Kompatsiaris; Vasiliki Kosmidou; Magda Tsolaki

    2014-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by cognitive deficits, problems in activities of daily living, and behavioral disturbances. Electroencephalogram (EEG) has been demonstrated as a reliable tool in dementia research and diagnosis. The application of EEG in AD has a wide range of interest. EEG contributes to the differential diagnosis and the prognosis of the disease progression. Additionally such recordings can add important information related to t...