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.


    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.

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    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 (United States)

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


    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. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology. (United States)

    Laurent, Cyril; Eddarkaoui, Sabiha; Derisbourg, Maxime; Leboucher, Antoine; Demeyer, Dominique; Carrier, Sébastien; Schneider, Marion; Hamdane, Malika; Müller, Christa E; Buée, Luc; Blum, David


    Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.

  5. 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


    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...

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

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    Laura Catalina Charry


    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.

  7. Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats. (United States)

    Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen


    Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

  8. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions. (United States)

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li


    Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

  9. Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's Disease-Like Murine Model. (United States)

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


    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.

  10. Loss of presenilin function causes Alzheimer's disease-like neurodegeneration in the mouse. (United States)

    Chen, Qian; Nakajima, Akira; Choi, Se Hoon; Xiong, Xiaoli; Tang, Ya-Ping


    Accumulating evidence has indicated that gain-of-function in beta-amyloid production may be not the necessary mechanism for mutant presenilin-1 (PS1) or PS2 to cause familial Alzheimer's disease (AD). In the present article, we show that conditional knockout of PS1 from the adult stage in the forebrain of mice with the PS2 null mutation triggers robust AD-like neurodegeneration including brain shrinkage, cortical and hippocampal atrophy,ventricular enlargement, severe neuronal loss, gliosis, tau hyperphosphorylation, neurofillament tangle-like structures, and intracellular filaments. Learning and memory functions in these mice are almost completely lost. Notably, there is no beta-amyloid deposition, indicating that presenilin dysfunction can directly cause neurodegeneration without the involvement of beta-amyloid. Furthermore, neurodegeneration occurs in a progressive manner following aging, suggesting that an accumulating effect of presenilin dysfunction over time might be a pathogenic mechanism for the involvement of mutant PS1/PS2 in causing AD. These results validate a mouse model characterized by the presence of many features of AD pathology. Furthermore, the demonstration of AD-like neurodegeneration in the absence of beta-amyloid deposition challenges the long-standing beta-amyloid cascade hypothesis and encourages an open debate on the role of beta-amyloid in causing AD. Most important, our results strongly suggest that to develop gamma-secretase inhibitors for the pharmacological treatment of AD may be not a reasonable strategy because antagonism of presenilin function may worsen neurodegeneration.

  11. Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models. (United States)

    Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook


    Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

  12. Acrolein induces Alzheimer's disease-like pathologies in vitro and in vivo. (United States)

    Huang, Ying-Juan; Jin, Ming-Hua; Pi, Rong-Biao; Zhang, Jun-Jie; Ouyang, Ying; Chao, Xiao-Juan; Chen, Mei-Hui; Liu, Pei-Qing; Yu, Jian-Chen; Ramassamy, Charles; Dou, Juan; Chen, Xiao-Hong; Jiang, Yi-Ming; Qin, Jian


    The pathologic mechanisms of Alzheimer's disease (AD) have not been fully uncovered. Acrolein, a ubiquitous dietary pollutant and by-product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD. Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo. We found Acrolein induced HT22 cells death in concentration- and time-dependent manners. Interestingly, Acrolein increased proteins' levels of amyloid precursor protein (APP), β-secretase (BACE-1) and the amyloid β-peptide transporter receptor for advanced glycation end products, and decreased A-disintegrin and metalloprotease (ADAM) 10 levels. In vivo, chronic oral exposure to Acrolein (2.5 mg/kg/day by intragastric gavage for 8 weeks) induced mild cognitive declination and pyknosis/atrophy of hippocampal neurons. The activity of superoxide dismutase was down-regulated while the level of malondialdehyde was up-regulated in rat brain. Moreover, Acrolein resulted in activation of astrocytes, up-regulation of BACE-1 in cortex and down-regulation of ADAM-10 in hippocampus and cortex. Taken together, our findings suggest that exposure to Acrolein induces AD-like pathology in vitro and in vivo. Scavenging Acrolein might be beneficial for the therapy of AD.

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

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    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.

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

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    Rania M. Bakkar


    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.

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


    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.

  16. Silencing GADD153/CHOP gene expression protects against Alzheimer's disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus.

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    Jaya R P Prasanthi

    Full Text Available Endoplasmic reticulum (ER stress is suggested to play a key role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD. Sustained ER stress leads to activation of the growth arrest and leucine zipper transcription factor, DNA damage inducible gene 153 (gadd153; also called CHOP. Activated gadd153 can generate oxidative damage and reactive oxygen species (ROS, increase β-amyloid (Aβ levels, disturb iron homeostasis and induce inflammation as well as cell death, which are all pathological hallmarks of AD. Epidemiological and laboratory studies suggest that cholesterol dyshomeostasis contributes to the pathogenesis of AD. We have previously shown that the cholesterol oxidized metabolite 27-hydroxycholesterol (27-OHC triggers AD-like pathology in organotypic slices. However, the extent to which gadd153 mediates 27-OHC effects has not been determined. We silenced gadd153 gene with siRNA and determined the effects of 27-OHC on AD hallmarks in organotypic slices from adult rabbit hippocampus. siRNA to gadd153 reduced 27-OHC-induced Aβ production by mechanisms involving reduction in levels of β-amyloid precursor protein (APP and β-secretase (BACE1, the enzyme that initiates cleavage of APP to yield Aβ peptides. Additionally, 27-OHC-induced tau phosphorylation, ROS generation, TNF-α activation, and iron and apoptosis-regulatory protein levels alteration were also markedly reduced by siRNA to gadd153. These data suggest that ER stress-mediated gadd153 activation plays a central role in the triggering of AD pathological hallmarks that result from incubation of hippocampal slices with 27-OHC. Our results add important insights into cellular mechanisms that underlie the potential contribution of cholesterol metabolism in AD pathology, and suggest that preventing gadd153 activation protects against AD related to cholesterol oxidized products.

  17. 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?

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    Liana Lisboa Fernandez


    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

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

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    Guilherme Riccioppo Rodrigues


    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.

  19. 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


    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.

  20. 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.


    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...

  1. Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice. (United States)

    Qiu, Hongyan; Zhong, Rujia; Liu, Hui; Zhang, Feng; Li, Song; Le, Weidong


    Recently, there is an increasing concern over the association between sleep disorders and Alzheimer's disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPP(swe)/PS1(ΔE9) transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β(1-42) production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.

  2. High-fat, high-sugar, and high-cholesterol consumption does not impact tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology. (United States)

    Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel


    Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, cholesterol, and sugar overconsumption on tau pathology in AD remain controversial. Using the hTau mice, a model of AD-like tau pathology, we assessed the effects of high-fat, high-cholesterol, and/or high-sugar diets on tau pathogenesis. Surprisingly, we found no effects of these compounds, even combined, on tau phosphorylation, O-GlcNAcylation, splicing, cleavage, and aggregation, suggesting that their overconsumption does not seem to worsen tau pathology in these mice.

  3. Transgenic expression of the amyloid-beta precursor protein-intracellular domain does not induce Alzheimer's Disease-like traits in vivo.

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    Luca Giliberto

    Full Text Available BACKGROUND: Regulated intramembranous proteolysis of the amyloid-beta precursor protein by the gamma-secretase yields amyloid-beta, which is the major component of the amyloid plaques found in Alzheimer's disease (AD, and the APP intracellular domain (AID. In vitro studies have involved AID in apoptosis and gene transcription. In vivo studies, which utilize transgenic mice expressing AID in the forebrain, only support a role for AID in apoptosis but not gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have further characterized several lines of AID transgenic mice by crossing them with human Tau-bearing mice, to determine whether over-expression of AID in the forebrain provokes AD-like pathologic features in this background. We have found no evidence that AID overexpression induces AD-like characteristics, such as activation of GSK-3beta, hyperphosphorylation of Tau and formation of neurofibrillary pathology. CONCLUSIONS/SIGNIFICANCE: Overall, these data suggest that AID transgenic mice do not represent a model that reproduces the overt biochemical and anatomo-pathologic lesions observed in AD patients. They can still be a valuable tool to understand the role of AID in enhancing the cell sensitivity to apoptotic stimuli, whose pathways still need to be characterized.

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

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


    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.

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


    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.

  6. Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.

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    Ronza Abdel Rassoul

    Full Text Available Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD. However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix. Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, "AD-like" animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays, we identified 47 genes that discriminated young from healthy old and "AD-like" animals. These findings were confirmed by principal component analysis (PCA. ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA with significant changes of expression in old and "AD-like" in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in "AD-like" animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the "AD-like" group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in "AD-like" animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in "AD-like" animals. These results open

  7. TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice. (United States)

    Devi, L; Ohno, M


    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.

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

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    Meng-qiu LI


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

  9. Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy. (United States)

    Dustin, Derek; Hall, Benjamin M; Annapragada, Ananth; Pautler, Robia G


    The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.

  10. Clinical symptoms and symptom signatures of Alzheimer's disease subgroups. (United States)

    Iqbal, Khalid; Flory, Michael; Soininen, Hilkka


    Alzheimer's disease (AD) is a multifactorial disorder that involves several different mechanisms. Over 99% of AD patients suffer from the sporadic form of the disease. Based on cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)(1-42), total tau, and ubiquitin--the markers associated with the histopathological hallmarks of the disease (Aβ plaques and abnormally hyperphosphorylated neurofibrillary tangles)--previous studies identified five subgroups of AD. Here we report the potential diagnostic predictive value of hallucination, hypokinesia, paranoia, rigidity, and tremors in aged individuals for AD and differences in the prevalence of these symptoms in the CSF marker-based subgroups of the disease. Analysis of 196 clinically diagnosed AD or Alzheimer with Lewy body, and 75 non-AD neurological and non-neurological control cases, all from a single center, showed that the presence of hallucination, hypokinesia, paranoia, rigidity, or tremors individually, or the presence of any of these, could diagnose AD with sensitivities and specificities of 14% and 99%; 30% and 99%; 15% and 99%; 16% and 100%; 16% and 96%; and 47% and 92%, respectively. The pattern of the prevalence of the above symptoms varied from AD subgroup to subgroup. Presence of any of these symptoms, as well as presence of each individual symptom except tremors, significantly differentiated AD subgroups from the predominantly control cluster. These findings encourage the exploration of hallucination, hypokinesia, paranoia, rigidity, and tremors in identifying various subgroups of AD for stratification of patients for clinical trials to develop therapeutic drugs. This study is for the special issue of the Journal of Alzheimer's Disease honoring Inge Grundke-Iqbal who made several seminal contributions in AD research.

  11. Clinically relevant drug interactions with anti-Alzheimer's drugs. (United States)

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo


    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. In conclusion, the concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice.

  12. Rationale and clinical data supporting nutritional intervention in Alzheimer's disease. (United States)

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


    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.

  13. Neurostimulation in Alzheimer's disease: from basic research to clinical applications. (United States)

    Nardone, Raffaele; Höller, Yvonne; Tezzon, Frediano; Christova, Monica; Schwenker, Kerstin; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco


    The development of different methods of brain stimulation provides a promising therapeutic tool with potentially beneficial effects on subjects with impaired cognitive functions. We performed a systematic review of the studies published in the field of neurostimulation in Alzheimer's disease (AD), from basic research to clinical applications. The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD. Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients.

  14. BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. (United States)

    Vassar, Robert


    β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the β-secretase enzyme required for the production of the neurotoxic β-amyloid (Aβ) peptide that is widely considered to have a crucial early role in the etiology of Alzheimer's disease (AD). As a result, BACE1 has emerged as a prime drug target for reducing the levels of Aβ in the AD brain, and the development of BACE1 inhibitors as therapeutic agents is being vigorously pursued. It has proven difficult for the pharmaceutical industry to design BACE1 inhibitor drugs that pass the blood-brain barrier, however this challenge has recently been met and BACE1 inhibitors are now in human clinical trials to test for safety and efficacy in AD patients and individuals with pre-symptomatic AD. Initial results suggest that some of these BACE1 inhibitor drugs are well tolerated, although others have dropped out because of toxicity and it is still too early to know whether any will be effective for the prevention or treatment of AD. Additionally, based on newly identified BACE1 substrates and phenotypes of mice that lack BACE1, concerns have emerged about potential mechanism-based side effects of BACE1 inhibitor drugs with chronic administration. It is hoped that a therapeutic window can be achieved that balances safety and efficacy. This review summarizes the current state of progress in the development of BACE1 inhibitor drugs and the evaluation of their therapeutic potential for AD.

  15. The animal models of dementia and Alzheimer's disease for pre-clinical testing and clinical translation. (United States)

    Anand, Akshay; Banik, Avijit; Thakur, Keshav; Masters, Colin L


    Dementia is a clinical syndrome with abnormal degree of memory loss and impaired ability to recall events from the past often characterized by Alzheimer's disease. The various strategies to treat dementia need validation of novel compounds in suitable animal models for testing their safety and efficacy. These may include novel anti-amnesic drugs derived from synthetic chemistry or those derived from traditional herbal sources. Multiple approaches have been adopted to create reliable animal models ranging from rodents to non-human primates, where the animals are exposed to a predetermined injury or causing genetic ablation across specific regions of brain suspected to affect learning functions. In this review various animal models for Alzheimer's disease and treatment strategies in development of anti dementia drugs are discussed and an attempt has been made to provide a comprehensive report of the latest developments in the field.

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

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    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.

  17. Diffusion tensor imaging for Alzheimer's disease: A review of concepts and potential clinical applicability


    Luciano de Gois Vasconcelos; Sonia Maria Dozzi Brucki; Andrea Parolin Jackowiski; Orlando Francisco Amodeo Bueno


    Abstract In view of the urgent need to identify an early and specific biomarker for Alzheimer's disease (AD), a PubMed database search was performed using the terms "Alzheimer disease" and "Diffusion Magnetic Resonance Imaging" to enable review of Diffusion tensor imaging (DTI) concepts and its potential clinical role in AD evaluation. Detailed analysis of selected abstracts showed that the main DTI measures, fractional anisotropy and apparent diffusion coefficient, indicators of fiber tract ...

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


    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.

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

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


    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.

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

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


    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.

  1. 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


    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

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

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    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

  3. Development of screening guidelines and clinical criteria for predementia Alzheimer's disease : the DESCRIPA study

    NARCIS (Netherlands)

    Visser, P.J.; Verhey, F.R.J.; Boada, M.; Bullock, R.; Deyn, P.P. de; Frisoni, G.B.; Frolich, L.; Hampel, H.; Jolles, J.; Jones, R.; Minthon, L.; Nobili, F.; Olde Rikkert, M.G.M.; Ousset, P.J.; Rigaud, A.S.; Scheltens, P.; Soininen, H.; Spiru, L.; Touchon, J.; Tsolaki, M.; Vellas, B.; Wahlund, L.O.; Wilcock, G.; Winblad, B.


    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

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


    Rogers, Heather; Arango Lasprilla, Juan Carlos


    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 ...

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


    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 Alzheimer's disease', n = 7) specifically targeted the clinically affected posterior brain regions, while (11)C-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation (n = 5) showed highest (18)F-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia ('language variant of Alzheimer's disease', n = 5) demonstrated asymmetric left greater than right hemisphere (18)F-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer's disease patients with all three positron emission tomography scans available, there was a strong negative association between (18)F-AV1451 and (18)F-FDG uptake (Pearson's r = -0.49 ± 0.07, P 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

  6. Clinical and neurocognitive aspects of hallucinations in Alzheimer's disease. (United States)

    El Haj, Mohamad; Roche, Jean; Jardri, Renaud; Kapogiannis, Dimitrios; Gallouj, Karim; Antoine, Pascal


    Due to their prevalence, hallucinations are considered as one of the most frequent psychotic symptoms in Alzheimer's disease (AD). These psychotic manifestations reduce patients' well-being, increase the burden of caregivers, contribute to early institutionalization, and are related with the course of cognitive decline in AD. Considering their consequences, we provide a comprehensive account of the current state of knowledge about the prevalence and characteristics of hallucinations in AD. We propose a comprehensive and testable theoretical model about hallucinations in AD: the ALZHA (ALZheimer and HAllucinations) model. In this model, neurological, genetic, cognitive, affective, and iatrogenic factors associated with hallucinations in AD are highlighted. According to the ALZHA model, hallucinations in AD first involve trait markers (i.e., cognitive deficits, neurological deficits, genetic predisposition and/or sensory deficits) to which state markers that may trigger these experiences are added (e.g., psychological distress and/or iatrogenic factors). Finally, we provide recommendations for assessment and management of these psychotic manifestations in AD, with the aim to benefit patients, caregivers, and health professionals.

  7. 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

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


    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

  9. Amyotrophic lateral sclerosis and Alzheimer's disease--clinical and neuropathological considerations in two cases. (United States)

    Rusina, R; Sheardová, K; Rektorová, I; Ridzon, P; Kulist'ák, P; Matej, R


    Amyotrophic lateral sclerosis (ALS) may be accompanied by cognitive impairment; when present, it is mainly in the form of frontotemporal impairment. We report on two cases with clinically defined ALS that subsequently developed dementia. Neuropathological examination showed not only the typical neuropathological hallmarks characteristic of ALS but, surprisingly, also showed neurofibrillary tangles and neuritic plaques in sufficient numbers to fulfill the diagnostic criteria of definite Alzheimer's disease.

  10. The future is now: model-based clinical trial design for Alzheimer's disease. (United States)

    Romero, K; Ito, K; Rogers, J A; Polhamus, D; Qiu, R; Stephenson, D; Mohs, R; Lalonde, R; Sinha, V; Wang, Y; Brown, D; Isaac, M; Vamvakas, S; Hemmings, R; Pani, L; Bain, L J; Corrigan, B


    Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease. CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

  11. [Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool sometimes useful in daily clinical practice of memory clinics for the diagnosis of complex cases]. (United States)

    Magnin, E; Dumurgier, J; Bouaziz-Amar, E; Bombois, S; Wallon, D; Gabelle, A; Lehmann, S; Blanc, F; Bousiges, O; Hannequin, D; Jung, B; Miguet-Alfonsi, C; Quillard, M; Pasquier, F; Peoc'h, K; Laplanche, J-L; Hugon, J; Paquet, C


    The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.

  12. Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease. (United States)

    Lim, Yen Ying; Maruff, Paul; Pietrzak, Robert H; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Szoeke, Cassandra; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C


    High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non

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


    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

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

    DEFF Research Database (Denmark)

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


    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....

  15. Odor identification and Alzheimer disease biomarkers in clinically normal elderly (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.


    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

  16. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges (United States)

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


    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.

  17. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges. (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee


    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.

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

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


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

  19. Advances in imaging-genetic relationships for Alzheimer's disease: clinical implications. (United States)

    Bagnoli, Silvia; Piaceri, Irene; Sorbi, Sandro; Nacmias, Benedetta


    Alzheimer's disease (AD) is the most common cause of dementia and represents a major public health problem. From a clinical perspective, AD is devastating to patients and their families. The genetic approach to the study of dementia undoubtedly continues to provide a significant contribution to understanding the pathogenesis, diagnosis and therapeutic perspectives, but also raises important ethical implications. With advances in new technology, including genetics and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined as an aid in the clinical diagnosis of AD, and also in presymptomatic evaluation. Here, we review some of the issues related to the neuroimaging-genetic relationship in AD with a possible clinical implication as a preclinical biomarker for dementia and also for tracking disease progression.

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

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


    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.

  1. Diffusion tensor imaging for Alzheimer's disease: A review of concepts and potential clinical applicability

    Directory of Open Access Journals (Sweden)

    Luciano de Gois Vasconcelos

    Full Text Available Abstract In view of the urgent need to identify an early and specific biomarker for Alzheimer's disease (AD, a PubMed database search was performed using the terms "Alzheimer disease" and "Diffusion Magnetic Resonance Imaging" to enable review of Diffusion tensor imaging (DTI concepts and its potential clinical role in AD evaluation. Detailed analysis of selected abstracts showed that the main DTI measures, fractional anisotropy and apparent diffusion coefficient, indicators of fiber tract integrity, provide a direct assessment of WM fibers and may be used as a new biomarker for AD. These findings were found to correlate with cognitive assessments, rates of AD progression and were also able to differentiate among groups including mild cognitive impairment, AD, and other dementias. Despite several consistent DTI findings in AD patients, there is still a lack of knowledge and studies on the DTI field. DTI is not yet ready for clinical use, and requires extensive further research in order to achieve this goal.

  2. Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of presenilin 2 gene. (United States)

    Marcon, Gabriella; Giaccone, Giorgio; Cupidi, Chiara; Balestrieri, Matteo; Beltrami, Carlo Alberto; Finato, Nicoletta; Bergonzi, Paolo; Sorbi, Sandro; Bugiani, Orso; Tagliavini, Fabrizio


    Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.

  3. Awareness of cognitive deficits and clinical competence in mild to moderate Alzheimer's disease: their relevance in clinical practice. (United States)

    Gambina, G; Bonazzi, A; Valbusa, V; Condoleo, M T; Bortolami, O; Broggio, E; Sala, F; Moretto, G; Moro, V


    Awareness of cognitive deficits and clinical competence were investigated in 79 mild to moderate Alzheimer's disease patients. Awareness was assessed by the anosognosia questionnaire for dementia, and clinical competence by specific neuropsychological tests such as trail making test-A, Babcock story recall test, semantic and phonemic verbal fluency. The findings show that 66 % of the patients were aware of memory deficits, while the 34 % were unaware. Deficit in awareness correlated with lower scores on the Mini Mental State Examination test that, in the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a significant predictor of level of awareness. None of the AD patients had fully preserved clinical competence, only 7 patients (9 %) had partially preserved clinical competence and 72 patients (91 %) had completely lost clinical competence. All the patients with partially preserved clinical competence (9 %) were aware of their memory deficit. The study indicates that neuropsychological tests used for the assessment of executive functions are not suitable for investigating clinical competence. Therefore, additional and specific tools for the evaluation of clinical competence are necessary. Indeed, these might allow clinicians to identify AD patients who, despite their deficits in selected functions, retain their autonomy of choice as well as recognize those patients who should proceed to the nomination of a legal representative.

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

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


    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)

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

    Directory of Open Access Journals (Sweden)

    Tomoyuki Nagata


    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.

  6. Dementia Pugilistica with clinical features of Alzheimer's disease Dementia pugilistica com características clínicas de doença de Alzheimer

    Directory of Open Access Journals (Sweden)

    Renata Areza-Fegyveres


    Full Text Available A 61-year-old ex-boxer presented with a three-year history of progressive memory decline. During a seven-year follow-up period, there was a continuous cognitive decline, very similar to that usually observed in Alzheimer's disease. Parkinsonian, pyramidal or cerebellar signs were conspicuously absent. Neuropathological examination revealed the typical features of dementia pugilistica: cavum septi pellucidi with multiple fenestrations, numerous neurofibrillary tangles in the cerebral isocortex and hippocampus (and rare senile plaques. Immunohistochemistry disclosed a high number of tau protein deposits and scarce beta-amyloid staining. This case shows that dementia pugilistica may present with clinical features practically undistinguishable from Alzheimer's disease.Um ex-boxeador de 61 anos apresentou-se com história de três anos de perda progressiva de memória e evoluiu com declínio cognitivo lentamente progressivo, sugestivo de doença de Alzheimer, durante seguimento de sete anos. Sinais parkinsonianos, piramidais ou cerebelares estiveram ausentes durante toda a evolução. Exame neuropatológico evidenciou características típicas de dementia pugilistica: cavum do septo pelúcido com múltiplas fenestrações, numerosos emaranhados neurofibrilares no isocórtex cerebral e hipocampo (e raras placas senis. Imuno-histoquímica confirmou número elevado de depósitos de proteína tau e raros de beta-amilóide. Este caso demonstra que dementia pugilistica pode apresentar quadro clínico indistinguível daquele da doença de Alzheimer.

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


    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.


    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...

  8. [Alzheimer and the discovery of Alzheimer's disease]. (United States)

    Zhagn, Lili; Li, Zhiping


    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.

  9. Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges. (United States)

    Wen, Ming Ming; El-Salamouni, Noha S; El-Refaie, Wessam M; Hazzah, Heba A; Ali, Mai M; Tosi, Giovanni; Farid, Ragwa M; Blanco-Prieto, Maria J; Billa, Nashiru; Hanafy, Amira S


    Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.

  10. Longitudinal clinical score prediction in Alzheimer's disease with soft-split sparse regression based random forest. (United States)

    Huang, Lei; Jin, Yan; Gao, Yaozong; Thung, Kim-Han; Shen, Dinggang


    Alzheimer's disease (AD) is an irreversible neurodegenerative disease and affects a large population in the world. Cognitive scores at multiple time points can be reliably used to evaluate the progression of the disease clinically. In recent studies, machine learning techniques have shown promising results on the prediction of AD clinical scores. However, there are multiple limitations in the current models such as linearity assumption and missing data exclusion. Here, we present a nonlinear supervised sparse regression-based random forest (RF) framework to predict a variety of longitudinal AD clinical scores. Furthermore, we propose a soft-split technique to assign probabilistic paths to a test sample in RF for more accurate predictions. In order to benefit from the longitudinal scores in the study, unlike the previous studies that often removed the subjects with missing scores, we first estimate those missing scores with our proposed soft-split sparse regression-based RF and then utilize those estimated longitudinal scores at all the previous time points to predict the scores at the next time point. The experiment results demonstrate that our proposed method is superior to the traditional RF and outperforms other state-of-art regression models. Our method can also be extended to be a general regression framework to predict other disease scores.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jagust, W.J.; Reed, B.R.; Seab, J.P.; Kramer, J.H.; Budinger, T.F. (Martinez Veterans Administration Medical Center, CA (USA))


    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer ({sup 123}I)-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.

  12. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease. (United States)

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D


    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, 65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  13. Alzheimer's or Depression: Could It Be Both? (United States)

    Alzheimer's or depression: Could it be both? Alzheimer's and depression have some similar symptoms. Proper treatment improves quality of life. By Mayo Clinic Staff Early Alzheimer's disease and depression share many ...

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

    NARCIS (Netherlands)

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


    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

  15. Psychosis in Alzheimer's Disease in the National Alzheimer's Disease Coordinating Center Uniform Data Set: Clinical Correlates and Association with Apolipoprotein E

    Directory of Open Access Journals (Sweden)

    Mary Ann A. DeMichele-Sweet


    Full Text Available Approximately 50% of late-onset Alzheimer's disease (AD patients develop psychosis (AD+P, a heritable phenotype associated with more rapid cognitive decline. Prior studies conflict regarding whether apolipoprotein E (APOE ϵ4 alleles are associated with AD+P, possibly due to small sample sizes, inconsistent diagnostic criteria, and different methodologies to assess psychosis. We used the National Alzheimer's Coordinating Center Uniform Data Set to evaluate the largest uniformly characterized sample of AD+P subjects studied to date for the association of APOE ϵ4 genotype, along with other demographic and clinical variables. Greater cognitive impairment and depressive symptoms were associated with AD+P, while the Caucasian race was protective. Neither APOE ϵ4 carrier status nor allele number was associated with psychosis. The AD+P phenotype is not associated with the APOE ϵ4 genotype. AD+P may represent a useful phenotype for the discovery of non-APOE ϵ4 genetic variation contributing to the risk of AD.

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

    Directory of Open Access Journals (Sweden)

    Pedro Andre Kowacs


    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.

  17. Alzheimer's Association (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 ...

  18. Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy.


    Wattmo, Carina; Minthon, Lennart; Wallin, Åsa


    BACKGROUND: There is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy. METHODS: This 3-year, prospective, observational, multicentre study included 1021 participants. Of the...

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

    Directory of Open Access Journals (Sweden)

    Luísa eAlves


    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.

  20. Cerebrospinal fluid biomarkers in Alzheimer's and Parkinson's diseases-From pathophysiology to clinical practice. (United States)

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


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

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

    NARCIS (Netherlands)

    Farkas, E; Luiten, PGM


    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

  2. Alzheimer's Project

    Medline Plus

    Full Text Available ... HBO's "THE ALZHEIMER'S PROJECT" will expose the Alzheimer's crisis facing our nation and drive concerned citizens to ... Institute on Aging at the National Institutes of Health in association with the Alzheimer's Association, The Fidelity ® ...

  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 Disease (United States)

    ... Emergency Room? What Happens in the Operating Room? Alzheimer Disease KidsHealth > For Kids > Alzheimer Disease A A A ... slow it down. When Someone You Love Has Alzheimer Disease You might feel sad or angry — or both — ...

  5. Alzheimer's Treatment (United States)

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Alzheimer's Treatment Past Issues / Winter 2015 Table of Contents Currently, there is no cure for Alzheimer's. Because it is a complex disease, scientists believe ...

  6. Renovating Alzheimer's: "Constructive" Reflections on the New Clinical and Research Diagnostic Guidelines (United States)

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


    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…

  7. Clinical features and mortality in patients with early-onset Alzheimer's disease.

    NARCIS (Netherlands)

    W.N. Samson; C.M. van Duijn (Cock); W.C.J. Hop (Wim); A. Hofman (Albert)


    textabstractIn a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was signif

  8. Useful Information on...Alzheimer's Disease. (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…

  9. 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


    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

  10. The clinical significance of plasmatic amyloid A{beta}-40 peptide levels in Alzheimer's disease patients treated with galantamine. (United States)

    Modrego, Pedro J; Monleon, Inmaculada; Sarasa, Manuel


    To date there are no conclusive reports on the usefulness of determining amyloid peptides in the serum of patients with Alzheimer's disease (AD). Only anecdotal works deal with the changes in the peptides produced by cholinesterase inhibitors. In this study, the authors investigated and studied the clinical significance of plasmatic Abeta-40 and Abeta-42 peptide levels in a series of 34 consecutive patients with AD. The baseline levels of the Abeta-40 peptide correlated negatively with the Mini Examen Cognoscitivo (Spanish version of the Mini-Mental test) score. Complete follow-up was possible in 22 patients. After 6 months of treatment with galantamine, the mean Abeta-40 peptide levels decreased from 31.86 to 24.22 pg/mL. The baseline levels of Abeta-40 were predictive of response to treatment in the Alzheimer's Disease Assessment Scale-Cognitive Subscale. The authors conclude that determining plasmatic Abeta-40 peptide levels could be useful in predicting and monitoring response to treatment in AD.

  11. The association between APOE epsilon4 and Alzheimer-type dementia among memory clinic patients is confined to those with a higher education. The DESCRIPA Study

    NARCIS (Netherlands)

    Vermeiren, A.P.; Bosma, H.; Visser, P.J.; Zeegers, M.P.; Graff, C.; Ewers, M.; Frisoni, G.B.; Frolich, L.; Hampel, H.; Jones, R.W.; Kehoe, P.G.; Lenoir, H.; Minthon, L.; Nobili, F.M.; Rikkert, M. Olde; Rigaud, A.S.; Scheltens, P.; Soininen, H.; Spiru, L.; Tsolaki, M.; Wahlund, L.O.; Vellas, B.; Wilcock, G.; Elias-Sonnenschein, L.S.; Verhey, F.R.J.


    We assessed the interaction between the APOE epsilon4 allele and education level in the etiology of Alzheimer's disease (AD) among memory clinic patients from the multicenter DESCRIPA study. Subjects (n = 544) were followed for 1 to 5 years. We used Cox's stratified survival modeling, adjusted for a

  12. Fully automated atlas-based hippocampal volumetry for detection of Alzheimer's disease in a memory clinic setting. (United States)

    Suppa, Per; Anker, Ulrich; Spies, Lothar; Bopp, Irene; Rüegger-Frey, Brigitte; Klaghofer, Richard; Gocke, Carola; Hampel, Harald; Beck, Sacha; Buchert, Ralph


    Hippocampal volume is a promising biomarker to enhance the accuracy of the diagnosis of dementia due to Alzheimer's disease (AD). However, whereas hippocampal volume is well studied in patient samples from clinical trials, its value in clinical routine patient care is still rather unclear. The aim of the present study, therefore, was to evaluate fully automated atlas-based hippocampal volumetry for detection of AD in the setting of a secondary care expert memory clinic for outpatients. One-hundred consecutive patients with memory complaints were clinically evaluated and categorized into three diagnostic groups: AD, intermediate AD, and non-AD. A software tool based on open source software (Statistical Parametric Mapping SPM8) was employed for fully automated tissue segmentation and stereotactical normalization of high-resolution three-dimensional T1-weighted magnetic resonance images. Predefined standard masks were used for computation of grey matter volume of the left and right hippocampus which then was scaled to the patient's total grey matter volume. The right hippocampal volume provided an area under the receiver operating characteristic curve of 84% for detection of AD patients in the whole sample. This indicates that fully automated MR-based hippocampal volumetry fulfills the requirements for a relevant core feasible biomarker for detection of AD in everyday patient care in a secondary care memory clinic for outpatients. The software used in the present study has been made freely available as an SPM8 toolbox. It is robust and fast so that it is easily integrated into routine workflow.

  13. 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)


    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)

  14. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

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


    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

  15. Alzheimer's: 7 Tips for Medical Visits (United States)

    ... Regular medical care is an important part of Alzheimer's treatment. Use these seven tips to stay on ... Clinic staff People who have dementia due to Alzheimer's disease need regular medical care to address a ...

  16. Can Occupational Therapy Slow Alzheimer's Decline? (United States)

    ... news/fullstory_162135.html Can Occupational Therapy Slow Alzheimer's Decline? Patients, caregivers may reap some benefits, but ... slow down the physical decline that comes with Alzheimer's disease, a new clinical trial suggests. The study ...

  17. Crystallographic study of PET radiotracers in clinical evaluation for early diagnosis of Alzheimers

    Directory of Open Access Journals (Sweden)

    Angela Altomare


    Full Text Available The title compound, C24H25NO3·2CH3OH, which crystallized as a methanol disolvate, has applications as a PET radiotracer in the early diagnosis of Alzheimer's disease. The dihedral angle between the biphenyl rings is 8.2 (2° and the heterocyclic ring adopts a half-chair conformation with the N atom adopting a pyramidal geometry (bond-angle sum = 327.6°. The C atoms of both methoxy groups lie close to the plane of their attached ring [deviations = 0.107 (6 and 0.031 (6 Å]. In the crystal, the components are linked by O—H...O and O—H...N hydrogen bonds, generating [010] chains. C—H...O interactions are also observed.

  18. Understanding Alzheimer's (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 ...

  19. 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 ...

  20. Alzheimer's Project

    Medline Plus

    Full Text Available ... Nonfiction Program. - 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 ® ...

  1. 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 ...

  2. Alzheimer's Project (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 ...

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


    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.

  4. A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer's Disease. (United States)

    Wang, Xiao-Dan; Lu, Hui; Shi, Zhihong; Cai, Li; Liu, Shuai; Liu, Shuling; Han, Tong; Wang, Ying; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong


    Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer's disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer's disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C-PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings.

  5. Cerebrolysin in Alzheimer's disease. (United States)

    Antón Álvarez, X; Fuentes, Patricio


    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.

  6. 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


    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

  7. Medication development for agitation and aggression in Alzheimer disease: review and discussion of recent randomized clinical trial design. (United States)

    Soto, Maria; Andrieu, Sandrine; Nourhashemi, Fati; Ousset, Pierre Jean; Ballard, Clive; Robert, Philippe; Vellas, Bruno; Lyketsos, Constantine G; Rosenberg, Paul B


    ABSTRACT Background: The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD. Methods: We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013. Results: We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of "clinically significant A/A." There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials. Conclusions: This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.

  8. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging. (United States)

    Hatashita, Shizuo; Yamasaki, Hidetomo


    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.

  9. 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.

  10. Neuroinflammation in Alzheimer's disease wanes with age

    Directory of Open Access Journals (Sweden)

    Hoozemans Jeroen JM


    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.

  11. Treatment of Alzheimer disease. (United States)

    Winslow, Bradford T; Onysko, Mary K; Stob, Christian M; Hazlewood, Kathleen A


    Alzheimer disease is the most common form of dementia, affecting nearly one-half [corrected] of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy.

  12. Alzheimer's Disease (United States)

    ... to note that Alzheimer's disease is not a normal part of aging. What Is Alzheimer's Disease? Video length: 2 min 29 sec Click to watch this video The course of Alzheimer’s disease—which symptoms appear and how quickly changes occur—varies from person to person. The time ...

  13. 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


    donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician's Interview-Based Impression of Change...... plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures). RESULTS: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds...... of declining were significantly reduced for donepezil-treated versus placebo patients (p donepezil-treated patients. CONCLUSION: In this population, donepezil treatment...

  14. Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer's Disease


    Francesco Panza; Vincenzo Solfrizzi; Davide Seripa; Imbimbo, Bruno P.; Madia Lozupone; Andrea Santamato; Chiara Zecca; Maria Rosaria Barulli; Antonello Bellomo; Alberto Pilotto; Antonio Daniele; Antonio Greco; Giancarlo Logroscino


    The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized f...

  15. Immunterapi mod Alzheimers sygdom

    DEFF Research Database (Denmark)

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers


    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing...

  16. 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.

  17. 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


    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...

  18. Treatments for Alzheimer's Disease (United States)

    ... 3900 Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? ... and move closer to a cure. Treatments for Alzheimer's disease Currently, there is no cure for Alzheimer's. But ...

  19. Alzheimer's Caregiving (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 ...

  20. 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 ...

  1. Alzheimer's Project

    Medline Plus

    Full Text Available ... Home > News & Events > Upcoming Events > HBO Alzheimer’s Project In the News Walk to End Alzheimer's Upcoming Events ... Memory Loss Tapes" was honored for Exceptional Merit in Nonfiction Filmmaking, while "Grandpa, Do You Know Who ...

  2. Are Clinical Diagnoses of Alzheimer's Disease and Other Dementias Affected by Education and Self-Reported Race? (United States)

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


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

  3. 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)


    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.)

  4. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao


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

  5. Pathological Hallmarks, Clinical Parallels, and Value for Drug Testing in Alzheimer's Disease of the APP[V717I] London Transgenic Mouse Model

    Directory of Open Access Journals (Sweden)

    An Tanghe


    Full Text Available The APP[V717I] London (APP-Ld mouse model recapitulates important pathological and clinical hallmarks of Alzheimer's disease (AD and is therefore a valuable paradigm for evaluating therapeutic candidates. Historically, both the parenchymal and vascular amyloid deposits, and more recently, truncated and pyroglutamate-modified Abeta3(pE-42 species, are perceived as important hallmarks of AD-pathology. Late stage symptoms are preceded by robust deficits in orientation and memory that correlate in time with Abeta oligomerization and GSK3-mediated phosphorylation of endogenous murine Tau, all markers that have gained considerable interest during the last decade. Clinical parallels with AD patients and the value of the APP-Ld transgenic mouse model for preclinical in vivo testing of candidate drugs are discussed.

  6. Senile dementia of the Alzheimer type

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  7. 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


    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

  8. Energy and the Alzheimer brain. (United States)

    Mamelak, Mortimer


    The high energy demands of the poorly myelinated long axon hippocampal and cortical neurons render these neurons selectively vulnerable to degeneration in Alzheimer's disease. However, pathology engages all of the major elements of the neurovascular unit of the mature Alzheimer brain, the neurons, glia and blood vessels. Neurons present with retrograde degeneration of the axodendritic tree, capillaries with string vessels and markedly reduced densities and glia with signs of inflammatory activation. The neurons, capillaries and astrocytes of the mature Alzheimer brain harbor structurally defective mitochondria. Clinically, reduced glucose utilization, decades before cognitive deterioration, betrays ongoing energy insufficiency. β-hydroxybutyrate and γ-hydroxybutyrate can both provide energy to the brain when glucose utilization is blocked. Early work in mouse models of Alzheimer's disease demonstrate their ability to reverse the pathological changes in the Alzheimer brain and initial clinical trials reveal their ability to improve cognition and every day function. Supplying the brain with energy holds great promise for delaying the onset of Alzheimer's disease and slowing its progress.

  9. Repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: clinical experience. (United States)

    Rabey, Jose Martin; Dobronevsky, Evgenia


    Alzheimer's disease (AD) is the most common type of dementia among the elderly. Common treatments available and non-pharmacological interventions have their limitations, and new therapeutic approaches are critically needed. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current-inducing modulation in cortical excitability. The previous clinical trials showed that combinations of rTMS and cognitive training (rTMS-COG), as provided by the NeuroAD medical device system, offer a novel, safe, and effective method improving mild-to-moderate AD patients. In this article, we present our experience with rTMS-COG treatment, in clinical settings, of 30 mild-to-moderate AD patients that received rTMS-COG commercial treatments in two clinics for 1-h daily sessions, 5 days per week, for 6 weeks (30 sessions). Five patients returned for a second treatment. ADAS-Cog and MMSE scores were measured pre- and post-treatments. The main analyses were conducted on patients who received 1 treatment (n = 30). Data received from the five returning patients were analyzed separately. The effect of rTMS-COG treatment was statistically significant regarding both ADAS-Cog (-2.4 point improvement, PV <0.001) and MMSE (+1.7 points improvement, PV <0.001) scores. About 80 % of patients gained some cognitive improvement following NeuroAD treatment, with more than 60 % improving by more than two points, for a minimum of 9 months. The Neuronix NeuroAD System was shown to be a safe and effective non-invasive modality for cognitive improvement of Alzheimer patients, with measurable outcomes lasting, in some of them, for up to 1 year, following completion of the 6-week daily intervention course (a carryover effect).

  10. Seven Stages of Alzheimer's (United States)

    ... Alzheimer's. LEARN MORE > Overview of disease progression The symptoms of Alzheimer's disease worsen over time, although the rate at ... the resources you need to cope with the symptoms and challenges of Alzheimer's. Find a chapter in your community Our free ...

  11. 老年痴呆症168例辨证治疗探讨%Clinical study of dialectical treatment of alzheimer' s disease

    Institute of Scientific and Technical Information of China (English)



    目的 探讨辩证治疗老年痴呆症临床疗效.方法 2008年1月-2009年10月诊治的老年痴呆症患者168例,随机分为辩证治疗组88例,常规治疗组80例,观察两组治疗前与治疗后进行认知功能、行为能力评价.结果 两组治疗前后认知功能、行为能力变化比较P<0.05,差异有统计学意义.结论 治疗老年痴呆症能够运用中医药进行辩证治疗,充分发挥中医整体观念,灵活运用辩证论治,能够取得良好的临床效果,减缓和改善老年痴呆症临床症状.%Objective To explore the dialectical treatment of Alzheimer's disease therapy. Methods January 2008-2009 years October dementia diagnosis and treatment of 168 patients were randomly divided into treatment group 88 cases of dialectic, the conventional treatment group 80 cases,both were observed before treatment and after treatment on cognitive function, behavior evaluation. Resuits Both before and after treatment of cognitive function, ability to change behavior comparison P < 0. 05 significant difference. Conclusions The treatment of Alzheimer's disease traditional Chinese medicine to use dialectical treatment, give full play to the whole concept of Chinese medicine, on the flexible use of dialectical treatment, to obtain good clinical effects, mitigation and improvement of clinical symptoms of dementia.

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

    DEFF Research Database (Denmark)

    Soininen, Hilkka; Mattila, Jussi; Koikkalainen, Juha


    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....

  13. 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


    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

  14. Weight loss and undernutrition in community-dwelling patients with Alzheimer's dementia: From population based studies to clinical management. (United States)

    Droogsma, E; van Asselt, D; De Deyn, P P


    Weight loss and undernutrition are commonly described in patients with Alzheimer's disease (AD) and have been associated with various adverse outcomes. Therefore, it is important to know what the best approach is to community-dwelling AD patients with a risk of developing a poor nutritional status; however, there is currently no evidence on which to base nutritional recommendations. Expert based recommendations are that the nutritional status should be part of the work-up of all AD patients. If weight loss of 5% or more has occurred in 3-6 months or if the mini-nutritional assessment (MNA) classifies a patient as undernourished, a nutritional intervention should be started. The intervention should be multifactorial and encompass treatment of the underlying proposed causes and risk factors of weight loss and undernutrition as well as improvement of the nutritional status by increasing energy and protein intake combined with daily physical activity.

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

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav


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

  16. 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;


    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...

  17. Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice (United States)

    Wang, Zigao; Xiong, Lu; Wan, Wenbin; Duan, Lijie; Bai, Xiaojing; Zu, Hengbing


    Alzheimer’s disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis. PMID:28228716

  18. Long-term Course of Alzheimer Disease in Patients Treated According to the Dutch Dementia Guideline at a Memory Clinic A "Real-Life" Study

    NARCIS (Netherlands)

    Droogsma, Erika; van Asselt, Dieneke; van Steijn, Jolanda; Diekhuis, Marjolein; Veeger, Nic; De Deyn, Peter P.


    Introduction:There is little knowledge of the long-term course of Alzheimer disease (AD) in light of current pharmacological and nonpharmacological interventions provided in a real-life setting.Methods:The Frisian Alzheimer's Disease Cohort study is a real-life study of the course of AD in patients

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

    DEFF Research Database (Denmark)

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


    The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine...... 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......-like phenotypes and ataxia syndromes, also in isolated cases....

  20. 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


    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......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...

  1. Recent developments in Alzheimer's disease therapeutics

    Directory of Open Access Journals (Sweden)

    Aisen Paul S


    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. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... without Alzheimer's — a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, ... COMMITMENT TO RESEARCH. Read More Alzheimer's Disease Facts in Each State The 2017 Alzheimer's Disease Facts and ...

  3. 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)


    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.

  4. 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


    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.

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


    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

  6. 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)


    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.)

  7. Alzheimer disease update. (United States)

    Matthews, Brandy R


    Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting more than 37 million people worldwide and increasing in incidence based on its primary risk factor, advancing age. A growing body of knowledge regarding amyloid and tau neuropathology, genetic and environmental risk modifiers, early and atypical clinical presentations, and the use of symptom-modifying medical and psychosocial therapies is available to aid in the diagnosis and management of patients with AD. Exciting recent advances in neurobiology render the areas of genetic susceptibility, biomarkers for early disease detection and assessment of disease progression, and novel therapeutic strategies to modify the natural history of the disease compelling, but in need of further study before implementation into routine clinical practice is feasible.

  8. Food, Eating and Alzheimer's (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 (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. Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease. (United States)

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


    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.

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

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


    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.

  12. The discovery of Alzheimer's disease


    Hippius, Hanns; Neundörfer, Gabriele


    On Novembers, 1306, a clinical psychiatrist and neuroanatomist, Alois Alzheimer, reported “A peculiar severe disease process of the cerebral cortex” to the 37th Meeting of South-West German Psychiatrists in Tubingen, He described a 50-year-old woman whom he had followed from her admission for paranoia, progressive sleep and memory disturbance, aggression, and confusion, until her death 5 years later. His report noted distinctive plaques and neurofibrillary tangles in the brain histology. It e...

  13. 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


    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.

  14. Metallostasis in Alzheimer's disease. (United States)

    Ayton, Scott; Lei, Peng; Bush, Ashley I


    2012 has been another year in which multiple large-scale clinical trials for Alzheimer's disease (AD) have failed to meet their clinical endpoints. With the social and financial burden of this disease increasing every year, the onus is now on the field of AD researchers to investigate alternative ideas to deliver outcomes for patients. Although several major clinical trials targeting Aβ have failed, three smaller clinical trials targeting metal interactions with Aβ have all shown benefit for patients. Here we review the genetic, pathological, biochemical, and pharmacological evidence that underlies the metal hypothesis of AD. The AD-affected brain suffers from metallostasis, or fatigue of metal trafficking, resulting in redistribution of metals into inappropriate compartments. The metal hypothesis is built upon a triad of transition elements: iron, copper, and zinc. The hypothesis has matured from early investigations showing amyloidogenic and oxidative stress consequences of these metals; recently, disease-related proteins, APP, tau, and presenilin, have been shown to have major roles in metal regulation, which provides insight into the pathway of neurodegeneration in AD and illuminates potential new therapeutic avenues.

  15. Alcohol consumption and mortality in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Berntsen, Sine; Kragstrup, Jakob; Siersma, Volkert


    OBJECTIVE: To investigate the association between alcohol consumption and mortality in patients recently diagnosed with mild Alzheimer's disease (AD). DESIGN: A post hoc analysis study based on a clinical trial population. SETTING: The data reported were collected as part of the Danish Alzheimer...


    NARCIS (Netherlands)



    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

  17. Vascular contribution to Alzheimer disease: predictors of rapid progression. (United States)

    Diomedi, Marina; Misaggi, Giulia


    Different courses of Alzheimer disease are observed in clinical practice. The rapidly progressive form could be associated with the presence of a major microcirculatory involvement and hemodynamic insufficiency. This short review aims to provide an overview of the current knowledge of cerebrovascular contribution to Alzheimer disease presentation and progression, hypothesizing the possible vascular markers of rapidly progressive form.

  18. 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)


    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

  19. Alzheimer's Disease Facts and Figures (United States)

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

  20. Genetics Home Reference: Alzheimer disease (United States)

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

  1. 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


    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.

  2. 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)



    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

  3. 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. (United States)

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


    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

  4. Biomarkers for early detection of Alzheimer disease. (United States)

    Barber, Robert C


    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.

  5. Molecular imaging of Alzheimer disease pathology. (United States)

    Kantarci, K


    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

  6. Rapidly progressive Alzheimer disease. (United States)

    Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga


    Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

  7. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases. (United States)

    Hölscher, Christian


    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable.

  8. 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


    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.

  9. Alzheimer's: Making Mealtimes Easier (United States)

    ... 2014. Shatenstein B, et al. Dietary intervention in older adults with early-stage Alzheimer dementia: Early lessons learned. The Journal of Nutrition, Health & Aging. 2008;12:461. Smith KL, et al. Weight loss and nutritional considerations in Alzheimer disease. 2008;27:381. Weight ...

  10. Study on Alzheimer's disease model

    Institute of Scientific and Technical Information of China (English)


    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.

  11. [Alzheimer's disease and human memory]. (United States)

    Eustache, F; Giffard, B; Rauchs, G; Chételat, G; Piolino, P; Desgranges, B


    Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way

  12. The rationale for deep brain stimulation in Alzheimer's disease. (United States)

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


    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.

  13. Interneurons in the human olfactory system in Alzheimer's disease. (United States)

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


    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.

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


    Wilcock, Donna M.


    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 ...

  15. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla


    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...

  16. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L


    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...

  17. Early psychosocial intervention in Alzheimer's disease

    DEFF Research Database (Denmark)

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


    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 in ...

  18. Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics. (United States)

    Athanasopoulos, Dimitrios; Karagiannis, George; Tsolaki, Magda


    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.

  19. 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


    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.

  20. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

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


    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia......, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded...... therapeutic or preventive strategies for Alzheimer's disease....

  1. Treatment for Alzheimer's diseases

    Directory of Open Access Journals (Sweden)

    Nina Arkadyevna Tyuvina


    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.

  2. [Biomarkers in Alzheimer's disease]. (United States)

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


    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.

  3. What Do We Know About Preventing Alzheimer's? (United States)

    ... or not things like exercise, diet, and "brain games" can help delay or prevent Alzheimer's disease and ... the Signs of Alzheimer's Disease? / Preventing Alzheimer's Disease / Quiz: Alzheimer's Disease / Treatment Winter 2015 Issue: Volume 9 ...

  4. 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.


    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

  5. Diabetes and Alzheimer's Linked (United States)

    ... and memory problems than are usually present in normal aging. Mild cognitive impairment may precede or accompany Alzheimer's ... medications on schedule. Evidence suggests diet and activity changes that ... slightly above normal (prediabetes) cut their risk of developing type 2 ...

  6. Communication and Alzheimer's (United States)

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

  7. Reliability of the Berg Balance Scale as a Clinical Measure of Balance in Community-Dwelling Older Adults with Mild to Moderate Alzheimer Disease: A Pilot Study. (United States)

    Muir-Hunter, Susan W; Graham, Laura; Montero Odasso, Manuel


    Objectif : Mesurer la fiabilité test-retest et interévaluateurs de l'échelle de Berg chez les adultes âgés qui résident dans la collectivité et qui sont atteints de la maladie d'Alzheimer au stade léger à modéré. Méthode : Un échantillon de 15 adultes (âge moyen de 80,20 [ET de 5,03] ans) atteints d'Alzheimer ont effectué trois tests d'équilibre : l'échelle de Berg (Berg Balance Scale), le test de lever et marcher chronométré (timed up-and-go [TUG]) et le test de portée fonctionnelle (Functional Reach Test). La fiabilité relative, à l'aide du coefficient de corrélation intraclasse (CCI) et la fiabilité absolue, à l'aide de l'erreur type de mesure (ETM) et des valeurs de changement détectable minimal (CDM95), ont été calculées; des courbes de Bland et Altman ont été construites pour évaluer la convergence interévaluateurs. L'intervalle de test-retest était d'une semaine. Résultats : En ce qui concerne l'échelle de Berg, les valeurs de fiabilité relative étaient de 0,95 (95% CI, 0,85 à 0,98) pour la fiabilité test-retest et de 0,72 (95% CI, 0,31 à 0,91) pour la fiabilité interévaluateurs; l'ETM était de 6,01 points et le CDM95 était de 16,66 points, tandis que la convergence interévaluateur était de 16,62 points. L'échelle de Berg a obtenu de meilleurs résultats que les tests de lever et marcher chronométré et de portée fonctionnelle, tests ayant une fiabilité établie pour l'Alzheimer en fiabilité test-retest. De 33% à 50% des participants avaient besoin de plus de directives que les instructions normalisées, car ils n'étaient pas capables de se souvenir des instructions de test. Conclusions : L'échelle de Berg a obtenu des valeurs de fiabilité relative qui appuient son utilité clinique, mais les valeurs de CDM95 et de convergence indiquent que cette échelle présente des limites en matière de rendement pour les cas d'Alzheimer. D'autres recherches visant l'optimisation de l'évaluation de l

  8. Cellular aging -Alzheimer


    Cuadrao Zavalela, Luis; Catedrático de patología General y Estomatológica UNMSM. Fac. Odontología.


    Histoncally, The term illness of Alzheimer was used if the suffering began befare the 65 years of age, and senile insanity if he/she made it la ter. Nevertheless at the present time, illness of Alzheimer refers to insanity related with the independent changes characteristic anatomopatológics of the principle age. The . macroscopic exam of the brain Shows expansion of the cerebral furrows, in general more marked in the regions frontal and storm. The important microscopic characteristics of th...

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

    KAUST Repository

    Gao, Zhao-Ming


    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.

  10. Influence of age on androgen deprivation therapy-associated Alzheimer's disease. (United States)

    Nead, Kevin T; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T; Leeper, Nicholas J; Shah, Nigam H


    We recently found an association between androgen deprivation therapy (ADT) and Alzheimer's disease. As Alzheimer's disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer's disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer's disease-free between non-ADT users age ≥70 versus those age Alzheimer's disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals Alzheimer's disease risk. Future work should investigate the ADT Alzheimer's disease association in advanced age populations given the greater potential clinical impact.

  11. Vaccination against Alzheimer disease: an update on future strategies. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Ítala Thaise Aguiar Holanda


    Full Text Available Estudio exploratório y descriptivo cujo objetivo fue clasificar el grado de demencia en ancianos afectados por la enfermedad de Alzheimer mediante el Clinical Dementia Rating y describir el perfil de estos a partir de informaciones del cuidador familiar. El Clinical Dementia Rating fue aplicado a 30 pacientes durante visita domiciliaria y sus miembros cuidadores integrantes de la Asociación de Alzheimer de Fortaleza, Ceará, Brasil, en 2009. Los resultados señalaron que los pacientes eran en su mayoría mujeres, casadas, de bajo nivel de educación y com grado de demencia grave. Se entiende la importancia de implementar programas multiprofesionales para pacientes y famílias, así como establecer acciones específicas de educación en salud y aplicación del Clinical Dementia Rating en la evaluación de estos.

  13. MRI morphometry in Alzheimer's disease. (United States)

    Matsuda, Hiroshi


    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.

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... for someone with Alzheimer's? Get Resources Cost to Nation The costs of health care and long-term ... of this disease in every state across the nation. Click below to see the effect that Alzheimer's ...

  15. Down Syndrome and Alzheimer's Disease (United States)

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

  16. Alzheimer's: When to Stop Driving (United States)

    Healthy Lifestyle Caregivers If your loved one has Alzheimer's, he or she may not be safe on ... for safe driving tends to decline with age, Alzheimer's disease accelerates this process dramatically. If you're ...

  17. African-Americans and Alzheimer's (United States)

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

  18. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  19. Palmomental reflex a relevant sign in early Alzheimer's disease diagnosis?


    Gabelle, Audrey; Gutierrez, Laure-Anne; Dartigues, Jean-François; Ritchie, Karen,; Touchon, Jacques; Berr, Claudine


    International audience; AbstractBackground: Sophisticated and expensive biomarkers are proposed for the diagnostic of Alzheimer disease (AD). Amyloid process seems to be early in AD and brain amyloid load affects the frontal lobe. Our objective is to determine if certain simple clinical signs especially frontal-related signs could help reach an earlier and better diagnosis. Methods: In the frame of the 3-City cohort, we conducted a nested case-control study comparing incident cases of Alzheim...

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

    Directory of Open Access Journals (Sweden)

    Donna M. Wilcock


    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.

  1. Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer's disease. (United States)

    Wilcock, Donna M


    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.

  2. 中西医结合治疗阿尔茨海默病的临床效果%Clinical effect of integrated traditional Chinese and western medicine treating Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    周志聪; 涂健铭; 刘宁; 伍剑萍


    Objective To investigate the clinical effect of integrated traditional Chinese and western medicine treating Alzheimer disease. Methods 100 patients with Alzheimer disease treated in our hospital and Yikang Geriatric Hospital were selected and they were divided into the experimental group (n=50) and the control group (n=50).The control group was treated with western medicine,the experimental group was treated with traditional Chinese medicine on the basis of the control group,the clinical effect in the two groups was compared. Results The total effective rate in the experimen-tal group was 92.0%,MMSE score was(22.63±1.54) points,ADL score was (39.17±3.65)points,the main clinical symptom total score (3.62±0.53) points,and there was a statistical difference of above-mentioned indicators in the two groups (P<0.05).There was no adverse reactions in the two groups. Conclusion The effect of integrated traditional Chinese and west-ern medicine treating Alzheimer disease is exact with higher safety.Ii is worthy of clinical promotion and application.%目的:探讨中西医结合治疗阿尔茨海默病的临床效果。方法收集本院及广州颐康老年病医院2010年1月~2014年1月收治的阿尔茨海默病患者100例,将患者按随机数字表法分为实验组、对照组,每组各50例。对照组单纯应用西药治疗,实验组在对照组基础上加用中药治疗,比较两组的临床效果。结果实验组的总有效率为92.0%,MMSE评分为(22.63±1.54)分,ADL评分为(39.17±3.65)分,临床主症状总分为(3.62±0.53)分,以上指标与对照组比较,差异有统计意义(P<0.05),两组均未见不良反应。结论中西医结合治疗阿尔茨海默病,效果确切,安全性高,值得临床推广应用。

  3. Alzheimer disease ethics--informed consent and related issues in clinical trials: results of a survey among the members of the Research Ethics Committees in Sweden. (United States)

    Peterson, Gunbrith; Wallin, Anders


    The rapid advances in biomedical sciences have induced special moral and ethical attitudes, which ought to be taken into account. One of the most essential issues is the principles for participation in research of subjects with reduced decision-making capacity. We conducted a questionnaire survey among members of the research ethics committees in Sweden to find out their attitudes to a range of ethical issues related to research on subjects with Alzheimer's disease. One hundred thirty-six of those approached responded (66%), and 117 of the responses (56%) were considered substantially complete. There were 16 questions with fixed reply alternatives. Some central questions concerned the informed consent process. With a few exceptions, there were no significant differences in attitudes between the experts and laypersons, between persons of different ages, and between men and women. However, women and laypersons were in general keener to preserve the patient's integrity and the experts were more willing than the laypersons to allow participation of subjects with dementia in placebo-controlled trials.

  4. Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates

    Directory of Open Access Journals (Sweden)

    Ezra Mulugeta


    Full Text Available We measured cerebrospinal fluid (CSF levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ and other CSF biomarkers in 107 patients with Alzheimer's disease (AD, dementia with Lewy body dementia (DLB, Parkinson's disease dementia (PDD, and normal controls (NC using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD. No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.

  5. Alzheimer disease: current concepts & future directions. (United States)

    Musiek, Erik S; Schindler, Suzanne E


    Alzheimer disease (AD) is the most common cause of dementia in individuals over age 65, and is expected to cause a major public health crisis as the number of older Americans rapidly expands in the next three decades. Herein, we review current strategies for diagnosis and management of AD, and discuss ongoing clinical research and future therapeutic directions in the battle against this devastating disease.

  6. 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


    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

  7. Alzheimer's disease and proton magnetic resonance spectroscopy of limbic regions: a suggestion of a clinical-spectroscopic staging Doença de Alzheimer e espectroscopia de prótons por ressonância magnética de regiões límbicas: sugestão de um estadiamento clínico-espectroscópico

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt


    Full Text Available OBJECTIVE: To compare magnetic resonance proton spectroscopic with clinical data and to propose a spectroscopic staging of Alzheimer's disease (AD. METHOD: Subjects (n=46, normals (12 and with AD (34, paired to age (CDR0-CDR3; AD diagnosis according to DSM-IV/NINCDS-ADRDA criteria; ¹H-MRS with Signa Horizon LX-GE, 1.5T; single voxel at hippocampal region/HCR and posterior cingulate area/PCA. RESULTS: Statistically significant decrease (pOBJETIVO: Comparar dados de espectroscopia de prótons por ressonância magnética com clínicos e propor um estadiamento espectroscópico da doença de Alzheimer (DA. MÉTODO: Sujeitos (n=46, normais (12 e com DA (34, emparelhados por idade (CDR0-CDR3; diagnóstico de DA de acordo com os critérios DSM-IV/NINCDS-ADRDA; ¹H-MRS com Signa Horizon LX-GE, 1.5T; voxel único em região hipocampal/RHC e área posterior do cíngulo/APC. RESULTADOS: Redução estatisticamente significativa (p<0.01 apenas de Naa/Cr - na RHC entre CDR0, CDR1+CDR2 e CDR3, e na APC entre CDR0 e CDR1+CDR2 em relação a CDR3. CONCLUSÃO: A RHC é a primeira a apresentar redução de Naa (CDR1. A APC é acometida mais tardiamente (CDR3. Esses valores declinam progressivamente de acordo com os estágios de gravidade. Considerando as disparidades entre a RHC e a APC é possível sugerir um estadiamento espectroscópico (metabólico (MS da DA como segue: MS0 (~CDR0=RHC e APC ambos normais, MS1-2 (~CDR1-2=RHC anormal e APC normal e MS3 (~CDR3=RHC e APC ambos anormais. Esses resultados permitem um diagnóstico precoce, o seguimento do processo degenerativo ao longo da evolução e sugerir um estadiamento espectroscópico relacionado aos estágios clínicos da DA.

  8. Lentivirus-expressed siRNA vectors against Alzheimer disease. (United States)

    Peng, Kevin A; Masliah, Eliezer


    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.

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

    Directory of Open Access Journals (Sweden)

    Florian Amtage


    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.

  10. Alzheimer's Dye Test? (United States)

    Science Teacher, 2005


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

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


    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.

  12. A role for oxidized DNA precursors in Huntington's disease-like striatal neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Gabriele De Luca


    Full Text Available Several human neurodegenerative disorders are characterized by the accumulation of 8-oxo-7,8-dihydroguanine (8-oxodG in the DNA of affected neurons. This can occur either through direct oxidation of DNA guanine or via incorporation of the oxidized nucleotide during replication. Hydrolases that degrade oxidized purine nucleoside triphosphates normally minimize this incorporation. hMTH1 is the major human hydrolase. It degrades both 8-oxodGTP and 8-oxoGTP to the corresponding monophosphates. To investigate whether the incorporation of oxidized nucleic acid precursors contributes to neurodegeneration, we constructed a transgenic mouse in which the human hMTH1 8-oxodGTPase is expressed. hMTH1 expression protected embryonic fibroblasts and mouse tissues against the effects of oxidants. Wild-type mice exposed to 3-nitropropionic acid develop neuropathological and behavioural symptoms that resemble those of Huntington's disease. hMTH1 transgene expression conferred a dramatic protection against these Huntington's disease-like symptoms, including weight loss, dystonia and gait abnormalities, striatal degeneration, and death. In a complementary approach, an in vitro genetic model for Huntington's disease was also used. hMTH1 expression protected progenitor striatal cells containing an expanded CAG repeat of the huntingtin gene from toxicity associated with expression of the mutant huntingtin. The findings implicate oxidized nucleic acid precursors in the neuropathological features of Huntington's disease and identify the utilization of oxidized nucleoside triphosphates by striatal cells as a significant contributor to the pathogenesis of this disorder.

  13. 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

  14. 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. (United States)

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


    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.

  15. The Potential role of marine derived food products on Alzheimer\\'s disese and cognitive decline

    Directory of Open Access Journals (Sweden)

    Mahsan Assadi


    Full Text Available Background: Alzheimer's disese is the most frequent cause of dementia and is one of important cause of mortality and morbidity in the world. Although, there are different therapeutic options for its treatment , the results of these therapies are disappointing. Omega-3 fatty acids in marine- derived food products, affect on different mechanisms, improve cognitive function, this study, effect Omega-3 fatty acids in marine- derived food products of cognitive disorders and Alzheimer's are reviewed. Methods: The method employed in this research was a systematic bibiliographic review,in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labeled studies using validated scales were retained. Results: Many studies have shown that Omega-3 fatty acids in marine- derived food products, affect by different mechanisms include decrease inflammation and oxidative stress, synaptogenesis, synaptic plasticity, and neurogenesis promotion in neuroprotection and improvement cognitive function and memory, also omega3 fatty acid could lead to a decrease in risk of Alzheimer's diseas and the other cognitive impairements. Conclusion: However, more and large clinical trials are needed to confirm the beneficial effects of omega 3 fatty acid supplementation on the management of Alzheimer's disease and cognitive decline.

  16. 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.


    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

  17. Alzheimer's Genes: Are You at Risk? (United States)

    Alzheimer's genes: Are you at risk? Several genes have been associated with Alzheimer's disease, but more research is needed. By Mayo ... Certain genes make you more likely to develop Alzheimer's disease. Genes control the function of every cell ...

  18. Caregiving for Alzheimer's Disease or Other Dementia (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 ...

  19. Impairments of auditory scene analysis in Alzheimer's disease. (United States)

    Goll, Johanna C; Kim, Lois G; Ridgway, Gerard R; Hailstone, Julia C; Lehmann, Manja; Buckley, Aisling H; Crutch, Sebastian J; Warren, Jason D


    Parsing of sound sources in the auditory environment or 'auditory scene analysis' is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer's disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis

  20. Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network. (United States)

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


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

  1. Rivastigmine in the treatment of hypersexuality in Alzheimer disease. (United States)

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


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

  2. Cognitive disability in alzheimer's disease and its management. (United States)

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


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

  3. Neuronal histamine and cognitive symptoms in Alzheimer's disease. (United States)

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


    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'.

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

    Institute of Scientific and Technical Information of China (English)

    Selina M(a)rdh


    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.

  5. Protein Unfolding and Alzheimer's (United States)

    Cheng, Kelvin


    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.

  6. Neuroinflammation in Alzheimer's disease


    Heneka, MT; Carson, MJ; Khoury, JE; Landreth, GE; Brosseron, F.; Feinstein, Dl; Jacobs, AH; Wyss-Coray, T; Vitorica, J; Ransohoff, RM; Herrup, K; Frautschy, SA; Finsen, B.; Brown, GC; Verkhratsky, A.


    © 2015 Elsevier Ltd. Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that severa...

  7. CSF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease. (United States)

    Ikeda, Masaki; Tashiro, Yuichi; Takai, Eriko; Kurose, Sachiko; Fugami, Naoko; Tsuda, Kazuhisa; Arisaka, Yukiko; Kodaira, Sayaka; Fujita, Yukio; Makioka, Kouki; Mizuno, Yuji; Shimada, Hirotaka; Harigaya, Yasuo; Takatama, Masamitsu; Amari, Masakuni; Yamazaki, Tsuneo; Yamaguchi, Haruyasu; Higuchi, Tetsuya; Okamoto, Koichi; Tsushima, Yoshito; Ikeda, Yoshio


    Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Aβ1-42, Aβ1-40 and Aβ1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Aβ1-42 and ratios of Aβ1-42/Aβ1-40 and Aβ1-42/Aβ1-38, and significant increases in CSF ptau-181 and ratios of ptau-181/Aβ1-42 and ptau-181/Aβ1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE ε4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB-PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Aβ may accumulate due to AD. Our results of AD-CSF markers including Aβ1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  9. 护理干预对轻中度老年阿尔茨海默病患者临床效果的影响%Effect of Nursing Intervention on Clinical Effect of Mild and Moderate Alzheimer's Disease Patients

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the effect of holistic nursing intervention in patients with mild to moderate AD. Methods Convenient selection 2012 January in 2014 December during treated in our hospital in patients with mild and moderate Alzheimer's disease 100 cases as the research object, according to the admission time has divided into the observation group (n = 50) and the control group (n = 50) were given holistic nursing intervention, routine nursing intervention, and the clinical results with the scores of MMSE and the QOL-AD, compared two groups of intervention. Results Afternursing, the observe groups of MMSE, QOL-AD score was (24.88±4.34)、(30.12±4.12), the control group was (21.68±3.10)、(26.34±3.22), with statistical significance (P<0.05). Conclusion In the clinical treatment of mild to moderate Alzheimer's disease, giving patients included staging evaluation, health education, cognitive training and preventive care, holistic nursing care, for im-proving the treatment effect has positive significance, it is worth popularizing in clinical nursing.%目的:探讨轻中度老年阿尔茨海默病(AD)实施护理干预的效果。方法方便选取2012年1月—2014年12月期间该院收治的轻中度老年阿尔茨海默病100例为研究对象,根据入院时间先后,分为观察组(n=50)与对照组(n=50),分别给予整体护理干预、常规护理干预,并用MMSE与QOL-AD评分,比较两组干预的临床效果。结果护理后,观察组MMSE评分、QOL-AD评分为(24.88±4.34)分、(30.12±4.12)分,对照组为(21.68±3.10)分、(26.34±3.22)分,差异有统计学意义(P<0.05)。结论在轻中度老年阿尔茨海默病的临床治疗中,给予患者包括分期评估、健康教育、认知训练和预防性护理在内的整体护理,对于改善治疗效果有积极意义,值得在临床护理中进一步推广应用。

  10. Down syndrome and Alzheimer's disease: Common pathways, common goals. (United States)

    Hartley, Dean; Blumenthal, Thomas; Carrillo, Maria; DiPaolo, Gilbert; Esralew, Lucille; Gardiner, Katheleen; Granholm, Ann-Charlotte; Iqbal, Khalid; Krams, Michael; Lemere, Cynthia; Lott, Ira; Mobley, William; Ness, Seth; Nixon, Ralph; Potter, Huntington; Reeves, Roger; Sabbagh, Marwan; Silverman, Wayne; Tycko, Benjamin; Whitten, Michelle; Wisniewski, Thomas


    In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments.

  11. A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease Efeitos do exercício físico sobre distúrbios neuropsiquiátricos e atividades instrumentais da vida diária em mulheres com doença de Alzheimer : um ensaio clínico controlado

    Directory of Open Access Journals (Sweden)

    Carla M. C. Nascimento


    Full Text Available OBJECTIVE: To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD. METHODS: The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. RESULTS: The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. CONCLUSION: The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.OBJETIVO: Analisar os efeitos de seis meses de intervenção de um programa de atividade física sobre os distúrbios neuropsiquiátricos e o desempenho nas atividades instrumentais da vida diária de idosos com Doença de Alzheimer (DA. MÉTODOS: Foram recrutados 20 pacientes nos estágios entre leve e moderado da DA. Segundo o escore clínico de demência (CDR, foram distribuídos em dois grupos: o grupo treinamento (GT, composto por dez mulheres que participaram de um program de exercícios físicos por um período de seis meses, e o grupo controle (GC, composto por dez outras participantes que não realizaram nenhum tipo de intervenção motora estruturada durante o mesmo período. Todas as participantes foram avaliadas por meio do Miniexame do Estado Mental, para obtenção da

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging – Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable ...

  13. Association of Alzheimer's disease and Chlamydophila pneumoniae. (United States)

    Stallings, Tiffany L


    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.

  14. In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial

    DEFF Research Database (Denmark)

    Jensen, Michael Gejl; Gjedde, Albert; Egefjord, Lærke


    with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [(11)C]PIB (PIB), CMRglc with [(18)F]FDG (FDG), and cognition with the WMS-IV scale ( NCT01469351). The PIB binding increased significantly in temporal lobe...... in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means...

  15. The spatio-temporal characteristics of different affected areas in the progression of Alzheimer disease:pathology, imaging and clinical relevance%阿尔茨海默病病程中不同受累部位的时间空间特点:病理、影像及临床表现相关性

    Institute of Scientific and Technical Information of China (English)

    纪东旭; 尹建忠


    The pathological changes of Alzheimer disease (Alzheimer disease, AD), such as the amyloid deposition, neurofibrillary tangles and large number of neuronal loss, appearance in the different brain regions in the order of time and space. When involving different brain regions, it may show the characteristic features in the functional and morphological aspects in this period, and would show the corresponding clinical symptoms.%阿尔茨海默病(Alzheimer disease,AD)的病理改变如淀粉样蛋白沉积、神经纤维缠结及大量神经元的丢失等在各个脑区的出现是有时间和空间顺序的。在累及不同脑区时,该脑区的功能学及形态学均有每个时期的特征性表现,同时会表现出相应的临床症状。

  16. Fibrinoid leukodystrophy (Alexander's disease-like disorder) in a young adult French bulldog. (United States)

    Ito, Tsuyoshi; Uchida, Kazuyuki; Nakamura, Masatoshi; Nakashima, Ko; Suzuki, Kazuhiko; Nakayama, Hiroyuki


    The paper describes clinical and pathological features of Alexander's disease (AD)-like disorder in a 1 year and 8 months old French bulldog. Clinically, the dog exhibited megaesophagus, emaciation and weakness without any specific neurological symptoms. The dog died of aspiration pneumonia. On the gross observation of formalin-fixed brain, discolored foci were observed in the white matter of the cerebellum and brain stem. Histologically, numerous Rothenthal fibers and hypertrophic astrocytes were distributed especially in the perivascular, subependymal and subpial area of both the cerebrum and cerebellum. The Rosenthal fibers were intensely immunopositive for GFAP and ubiquitin. Demyelination of the white matter was occasionally found in the brain stem. The present case is likely to be categorized in the adult form of AD, though previous AD-like cases in dogs were in the juvenile form.

  17. 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


    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.

  18. Psychiatric Symptoms in Adults with Down Syndrome and Alzheimer's Disease (United States)

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


    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…

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

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta


    The inability to effectively halt or cure Alzheimer's disease (AD), exacerbated by the recent failures of high-profile clinical trials, emphasizes the urgent need to understand the complex biochemistry of this major neurodegenerative disease. In this paper, ten central, current challenges...

  20. 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.;


    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)....

  1. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine (United States)

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

  2. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine (United States)

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease 7 Warning Signs of Alzheimer's Past Issues / Fall 2010 Table of Contents The ... Suncoast Gerontology Center, University of South Florida. How Alzheimer's Changes the Brain The only definite way to ...

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

    DEFF Research Database (Denmark)

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


    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...

  4. Alzheimer's disease camouflaged by histrionic personality disorder. (United States)

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


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

  5. 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


    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.

  6. The role of chemical engineering in medicinal research including Alzheimer's. (United States)

    Kontogeorgis, Georgios M


    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.

  7. 多奈哌齐联合盐酸美金刚治疗阿尔茨海默病的临床研究%Clinical Study of Donepezil and Memantine Hydrochloride in the Treatment of Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)



    目的:探讨多奈哌齐联合盐酸美金刚治疗阿尔茨海默病的的临床疗效和安全性。方法78例阿尔茨海默病患者随机分为观察组与对照组两组各39例,观察组患者采用多奈哌齐联合盐酸美金刚治疗,对照组患者采用多奈哌齐治疗,采用AD 评估量表-认知部分(ADAS-cog)、简易智能精神状态检查量表(MMSE)和日常生活活动能力量表(ADL)评定患者治疗前后的临床效果。结果治疗后,两组患者ADAS-cog、MMES和ADL量表评分与治疗前相比均有所改善(P<0.05);观察组患者改善效果好于对照组(P<0.05)。两组不良反应发生情况相比差异无统计学意义(P>0.05)。结论多奈哌齐联合盐酸美金刚治疗阿尔茨海默病疗效显著,能显著改善患者的认知功能和行为能力,并且具有良好的安全性。%Objective To explore the clinical effects and security of donepezil combined with memantine in the treatment of alzheimer’s disease. Methods78 cases of Alzheimer's disease patients were randomly divided into observation group and control group 39 cases in each group, the patients in the observation group with donepezil and memantine hydrochloride in the treatment and control group were treated with donepezil, table - cognitive (ADAS-cog), Mini Mental State Examination (MMSE) and activities of daily living ability scale (ADL) before and after treatment in patients with the clinical effect assessment by the assessment.ResultsAfter treatment, The scores of ADAS-cog, MMSE and ADL were improved in both groups (P0.05).Conclusion Donepezil combined with memantine in the treatment of alzheimer’s disease has signiifcant curative effect, can signiifcantly improve the patients' cognitive function and behavior ability, and good security.

  8. The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician. (United States)

    Martino, Davide; Stamelou, Maria; Bhatia, Kailash P


    A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features ('red flags') that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive-behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.

  9. Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease. (United States)

    Venigalla, Madhuri; Gyengesi, Erika; Münch, Gerald


    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.

  10. Identification of Genes Involved in the Early Stages of Alzheimer Disease Using a Neural Network Algorithm

    Directory of Open Access Journals (Sweden)



    Full Text Available Alzheimer disease is one form of dementia in old age. Alzheimer disease, the incurable disease, which is usually in the seventh decade of human life, shows its symptoms. The disease may be present for years without clinical symptoms. The current study identified the genes with altered expression in patients with Alzheimer disease. The important sequence of each gene in Alzheimer disease was found and introduced as a biomarker of this disease. The present study used microarray libraries related to Alzheimer disease. Finally, the data were weighted using 10 data mining methods, including methods such as support vector machine (SVM, deviation, information gain ratio and the Gini coefficient. Sequences with least two algorithm weights above 0.5 were selected as the most important sequences. Then, a neural network algorithm (neural net, auto multilayer perceptron and perceptron was run on 11 data bases from the weighted perceptron algorithm, resulting in a careful 97% best performance.

  11. Heterogeneity of neuroanatomical patterns in prodromal Alzheimer's disease: links to cognition, progression and biomarkers. (United States)

    Dong, Aoyan; Toledo, Jon B; Honnorat, Nicolas; Doshi, Jimit; Varol, Erdem; Sotiras, Aristeidis; Wolk, David; Trojanowski, John Q; Davatzikos, Christos


    Individuals with mild cognitive impairment and Alzheimer's disease clinical diagnoses can display significant phenotypic heterogeneity. This variability likely reflects underlying genetic, environmental and neuropathological differences. Characterizing this heterogeneity is important for precision diagnostics, personalized predictions, and recruitment of relatively homogeneous sets of patients into clinical trials. In this study, we apply state-of-the-art semi-supervised machine learning methods to the Alzheimer's disease Neuroimaging cohort (ADNI) to elucidate the heterogeneity of neuroanatomical differences between subjects with mild cognitive impairment (n = 530) and Alzheimer's disease (n = 314) and cognitively normal individuals (n = 399), thereby adding to an increasing literature aiming to establish neuroanatomical and neuropathological (e.g. amyloid and tau deposition) dimensions in Alzheimer's disease and its prodromal stages. These dimensional approaches aim to provide surrogate measures of heterogeneous underlying pathologic processes leading to cognitive impairment. We relate these neuroimaging patterns to cerebrospinal fluid biomarkers, white matter hyperintensities, cognitive and clinical measures, and longitudinal trajectories. We identified four such atrophy patterns: (i) individuals with largely normal neuroanatomical profiles, who also turned out to have the least abnormal cognitive and cerebrospinal fluid biomarker profiles and the slowest clinical progression during follow-up; (ii) individuals with classical Alzheimer's disease neuroanatomical, cognitive, cerebrospinal fluid biomarkers and clinical profile, who presented the fastest clinical progression; (iii) individuals with a diffuse pattern of atrophy with relatively less pronounced involvement of the medial temporal lobe, abnormal cerebrospinal fluid amyloid-β1-42 values, and proportionally greater executive impairment; and (iv) individuals with notably focal involvement of the medial

  12. 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


    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.

  13. The burden of Alzheimer's disease. (United States)

    Burns, Alistair


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  15. 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


    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 (, Clinical (, and Chinese Clinical Trial Registry ( 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.

  16. New cardiovascular targets to prevent late onset Alzheimer disease. (United States)

    Claassen, Jurgen A H R


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

  17. Alzheimer's disease, apolipoprotein E and hormone replacement therapy. (United States)

    Depypere, H; Vierin, A; Weyers, S; Sieben, A


    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  18. Alzheimer's Disease | NIH MedlinePlus the Magazine (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 ...

  19. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  20. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... action. Become an advocate SPECIAL REPORT — ALZHEIMER'S DISEASE: THE NEXT FRONTIER In the history of medicine, one ... physician I am a researcher Message boards Get the facts 10 warning signs & symptoms What is dementia ...

  1. Alzheimer's Disease Facts and Figures

    Medline Plus

    Full Text Available ... to those with Alzheimer's and other dementias, a contribution to the nation valued at $230.1 billion. ... NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures ...

  2. Mucosal disease-like lesions in sheep infected with Border disease virus. (United States)

    Monies, R J; Paton, D J; Vilcek, S


    An enteric disease characterised by diarrhoea and ill thrift affected 12 of a flock of 700 six- to 12-month-old ewe lambs in Cornwall between December 1996 and September 1997. The affected lambs were undersized, became thin and suffered an unremitting diarrhoea until they died. The illness lasted for three to 14 days, although, with hindsight, the owner considered that the lambs had been below average size before the enteric signs developed. The outbreak ceased only as a result of the dispersal sale of the flock as breeding ewes. The flock had been purchased from different sources, but 11 of the cases occurred in a group of 40 purchased from one source. Postmortem, the alimentary changes resembled mucosal disease in cattle, and immunostaining of histological sections of the affected tissues revealed pestiviral antigen. Non-cytopathic pestiviruses were isolated from the lesions of two of the affected lambs and from the blood of several clinically normal ewe lambs from the same group. All the pestivirus isolates were typed as Border disease virus.

  3. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone (United States)

    Li, Lei; Ji, Dong; Ji, Ying-Jie; Li, Chen; Gao, Xu-Dong; Wang, Li-Fu; Zhao, Min; Duan, Xue-Zhang; Duan, Hui-Juan


    During the 2014 Ebola virus disease (EVD) outbreak, less than half of EVD-suspected cases were laboratory tested as Ebola virus (EBOV)-negative, but disease identity remained unknown. In this study we investigated the etiology of EVD-like illnesses in EBOV-negative cases. From November 13, 2014 to March 16, 2015, EVD-suspected patients were admitted to Jui Government Hospital and assessed for EBOV infection by real-time PCR. Of 278 EBOV negative patients, 223 (80.21%), 142 (51.08%), 123 (44.24%), 114 (41.01%), 59 (21.22%), 35 (12.59%), and 12 (4.32%) reported fever, headache, joint pain, fatigue, nausea/vomiting, diarrhea, hemorrhage, respectively. Furthermore, 121 (43.52%), 44 (15.83%), 36 (12.95%), 33 (11.87%), 23 (8.27%), 10 (3.60%) patients were diagnosed as infection with malaria, HIV, Lassa fever, tuberculosis, yellow fever, and pneumonia, respectively. No significant differences in clinical features and symptoms were found between non-EVD and EVD patients. To the best of our knowledge, the present study is the first to explore the etiology of EVD-like illnesses in uninfected patients in Sierra Leone, highlighting the importance of accurate diagnosis to EVD confirmation. PMID:27058894

  4. Alzheimer's disease and stigmatization

    Directory of Open Access Journals (Sweden)

    Dimitrios Kosmidis


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

  5. [Music therapy and Alzheimer disease]. (United States)

    Tromeur, Emilie


    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.

  6. The Danish Alzheimer intervention study

    DEFF Research Database (Denmark)

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


    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...

  7. Neuroinhibitory molecules in Alzheimer's disease. (United States)

    Larner, A J; Keynes, R J


    Aberrant neurite growth is one of the neuropathological signatures of the Alzheimer's disease brain, both around amyloid plaques and in the cortical neuropil. Disruption of neuroinhibitory or repulsive growth and guidance signals, as well as of neurotrophic or permissive signals, may contribute to this dystrophic growth. Hence, therapeutic efforts directed exclusively at restoring neurotrophic activity are unlikely to meet with success. The molecular species responsible for neuroinhibitory effects in the Alzheimer's disease brain are beginning to be elucidated.

  8. periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. (United States)

    Rios, Hector; Koushik, Shrinagesh V; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q; Conway, Simon J


    Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (peri(lacZ)) embryos are grossly normal. Postnatally, however, approximately 14% of the nulls die before weaning and all of the remaining peri(lacZ) nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the peri(lacZ) nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses.

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


    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.

  10. 18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy. (United States)

    Passamonti, Luca; Vázquez Rodríguez, Patricia; Hong, Young T; Allinson, Kieren S J; Williamson, David; Borchert, Robin J; Sami, Saber; Cope, Thomas E; Bevan-Jones, W Richard; Jones, P Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D; Aigbirhio, Franklin I; O'Brien, John T; Rowe, James B


    The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer (18)F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the (18)F-AV-1451 autoradiographic binding in post mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the (18)F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased (18)F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P Alzheimer's disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t's > 2.2, P's Alzheimer's disease, (18)F-AV-1451 binding was elevated in the midbrain (t = 2.1, P 2.7, P's Alzheimer's disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy.

  11. [A new definition for Alzheimer's disease]. (United States)

    Dubois, Bruno


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

  12. [Locomotor activity and learning and memory abilities in Alzheimer's disease induced by aluminum in an acid environment in zebrafish]. (United States)

    He, Xiong; Zhong, Zhao-Ming; Che, Yi


    We investigated the contribution of locomotor activity and learning and memory abilities to Alzheimer's disease induced by metal neurotoxicity. The metal neurotoxicity model was established by using locomotor activity tests and activity-avoidance conditioning paradigms, and observing changes in zebrafish behaviors after exposure to 50 μg/L of AlCl(3) with different pH values (pH 7.8, pH 6.8 and pH 5.8) for 24 hours and 96 hours. The results showed Alzheimer's disease-like behavior in locomotor activity tests and activity-avoidance conditioning paradigms by zebrafish receiving AlCl(3) in pH 5.8 significantly decreased compared to the control group and groups receiving AlCl(3) in pH 7.8 and pH 6.8 for 96 hours and 24 hours. These results provide evidences that exposure to AlCl( 3) in an acid environment can influence locomotor activity and learning and memory abilities in zebrafish. In addition, exposure time and concentration of Al induced neurotoxicity and damaged the brain area of memory, resulting in Alzheimer's disease-like behavior.

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

    Directory of Open Access Journals (Sweden)

    Antônio Lúcio Teixeira-Jr


    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.

  14. A conceptual framework and ethics analysis for prevention trials of Alzheimer Disease. (United States)

    Peters, Kevin R; Lynn Beattie, B; Feldman, Howard H; Illes, Judy


    As our understanding of the neurobiology of Alzheimer Disease deepens, it has become evident that early intervention is critical to achieving successful therapeutic impact. The availability of diagnostic criteria for preclinical Alzheimer Disease adds momentum to research directed at this goal and even to prevention. The landscape of therapeutic research is thus poised to undergo a dramatic shift in the next 5-10 years, with clinical trials involving subjects at risk for Alzheimer Disease who have few or no symptoms. These trials will also likely rely heavily on genetics, biomarkers, and or risk factor stratification to identify individuals at risk for Alzheimer Disease. Here, we propose a conceptual framework to guide this next generation of pharmacological and non-pharmacological clinical pursuit, and discuss some of the foreseeable ethical considerations that may accompany them.

  15. Immunotherapy against amyloid pathology in Alzheimer's disease. (United States)

    Galimberti, Daniela; Ghezzi, Laura; Scarpini, Elio


    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.

  16. Elder Care for Alzheimer's: Choosing a Provider (United States)

    ... elder care center for a loved one with Alzheimer's. What should I look for when considering a ... provide an opportunity for your loved one with Alzheimer's to receive assistance and therapeutic activities in a ...

  17. Grief and Loss as Alzheimer's Progresses (United States)

    ... or share your name. Grief and Loss as Alzheimer's Progresses Tweet Bookmark this page | Email | Print It ... and grief as their life is changed by Alzheimer's. You're entitled to these emotions and may ...

  18. Link Seen Between Concussions and Alzheimer's (United States)

    ... fullstory_163025.html Link Seen Between Concussions and Alzheimer's But study didn't prove head injuries cause ... mental decline of people already at risk for Alzheimer's disease? In a new study, researchers examined 160 ...

  19. Imagine stopping the progression of Alzheimer's (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 ...

  20. Alzheimer's May Hamper Ability to Perceive Pain (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. ...

  1. 10 Early Signs and Symptoms of Alzheimer's (United States)

    ... be a symptom of Alzheimer's or another dementia . Alzheimer's is a brain disease that causes a slow decline in memory, thinking and reasoning skills. There are 10 warning signs and symptoms. Every individual may experience one or more of ...

  2. Fewer Advanced Alzheimer's Patients on Feeding Tubes (United States)

    ... 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 ...

  3. A Bayesian network decision model for supporting the diagnosis of dementia, Alzheimer׳s disease and mild cognitive impairment. (United States)

    Seixas, Flávio Luiz; Zadrozny, Bianca; Laks, Jerson; Conci, Aura; Muchaluat Saade, Débora Christina


    Population aging has been occurring as a global phenomenon with heterogeneous consequences in both developed and developing countries. Neurodegenerative diseases, such as Alzheimer׳s Disease (AD), have high prevalence in the elderly population. Early diagnosis of this type of disease allows early treatment and improves patient quality of life. This paper proposes a Bayesian network decision model for supporting diagnosis of dementia, AD and Mild Cognitive Impairment (MCI). Bayesian networks are well-suited for representing uncertainty and causality, which are both present in clinical domains. The proposed Bayesian network was modeled using a combination of expert knowledge and data-oriented modeling. The network structure was built based on current diagnostic criteria and input from physicians who are experts in this domain. The network parameters were estimated using a supervised learning algorithm from a dataset of real clinical cases. The dataset contains data from patients and normal controls from the Duke University Medical Center (Washington, USA) and the Center for Alzheimer׳s Disease and Related Disorders (at the Institute of Psychiatry of the Federal University of Rio de Janeiro, Brazil). The dataset attributes consist of predisposal factors, neuropsychological test results, patient demographic data, symptoms and signs. The decision model was evaluated using quantitative methods and a sensitivity analysis. In conclusion, the proposed Bayesian network showed better results for diagnosis of dementia, AD and MCI when compared to most of the other well-known classifiers. Moreover, it provides additional useful information to physicians, such as the contribution of certain factors to diagnosis.

  4. Imaging markers for Alzheimer disease (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


    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

  5. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing


    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.

  6. Turning principles into practice in Alzheimer's disease


    Lindesay, James; Bullock, Roger; Daniels, Hugo; Emre, Murat; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus


    Abstract 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 Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most import...

  7. 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


    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.

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

    LENUS (Irish Health Repository)

    Hampel, Harald


    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: ( Identifier: ISRCTN72046462.

  9. Reduced miR-512 and the Elevated Expression of Its Targets cFLIP and MCL1 Localize to Neurons With Hyperphosphorylated Tau Protein in Alzheimer Disease. (United States)

    Mezache, Louisa; Mikhail, Madison; Garofalo, Michela; Nuovo, Gerard J


    The cause for the neurofibrillary tangles and plaques in Alzheimer disease likely relates to an abnormal accumulation of their key components, which include β-amyloid and hyperphosphorylated tau protein. We segregated Alzheimer brain sections from people with end-stage disease into those with abundant hyperphosphorylated tau protein and those without and compared each to normal brains for global microRNA patterns. A significant reduced expression of several microRNAs, including miR-512, was evident in the Alzheimer brain sections with abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and each colocalized to neurons with the abnormal tau protein. Analysis for apoptosis including activated caspase-3, increased caspase-4 and caspase-8, apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a marker of neuroprogenitor cells, was significantly reduced in the Alzheimer sections that contained the hyperphosphorylated tau. These results suggest that a basic defect in Alzheimer disease may be the reduced microRNA-driven increased expression of proteins that may alter the apoptotic/antiapoptotic balance of neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins such as hyperphosphorylated tau that ultimately prevent normal neuronal function and lead to disease symptomatology.

  10. [Aluminum, hypothetic cause of Alzheimer disease]. (United States)

    Pailler, F M; Bequet, D; Corbé, H; Giudicelli, C P


    A great deal of research has focused on aluminium as a putative causative factor in Alzheimer's disease. We measured by atomic absorption spectrophotometry aluminium levels in blood, urine and cerebrospinal fluid from 15 patients with Alzheimer's disease, compared with 20 control individuals. There were no statistically significant differences between the two groups. This suggests that aluminium is not a causative factor for Alzheimer's disease.

  11. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients (United States)

    Kälin, Andrea M.; Park, Min T. M.; Chakravarty, M. Mallar; Lerch, Jason P.; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D.; Kollias, Spyros; Nitsch, Roger M.; Gietl, Anton F.; Unschuld, Paul G.; Hock, Christoph; Leh, Sandra E.


    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59–82, 47.8% female), future converters at baseline (n = 10, age range 66–84, 90% female) and at time of conversion (age range 68–87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61–81, 47.8% female; n = 10, age range 66–82, 80% female; n = 10, age range 68–82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced

  12. Nonliteral language in Alzheimer dementia: a review. (United States)

    Rapp, Alexander M; Wild, Barbara


    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.

  13. Alzheimer's disease under the mask of stroke

    Directory of Open Access Journals (Sweden)

    A. A. Naumenko


    Full Text Available Cognitive impairments (CIs are common in poststroke patients. The basis for this condition is frequently a neurodegenerative process and most often Alzheimer's disease (AD. Stroke may promote the manifestation of clinically asymptomatic AD, worsen prestroke cognitive deficit or merely manifest prestroke CIs.The paper discusses the epidemiology, risk factors, and pathogenesis of poststroke CIs, current methods for its diagnosis, as well as symptomatic and pathogenetic treatment. The most informative method for the diagnosis of poststroke CIs is neuropsychological examination that should be made in the early poststroke period (if the patient's consciousness is clear. The most common screening tests include mini-mental state examination (the most sensitive to evaluate cognitive dysfunction in Alzheimer type dementias and the Montreal cognitive assessment. Magnetic resonance imaging of the brain, positron emission tomography, cerebrospinal fluid examination, and genetic testing are used to reveal AD at its preclinical stages. Preventive measures include regular physical activity, a balanced diet, and sufficient mental workload. The prevention of stroke and other cardiovascular diseases are also important.The major groups of drugs used to treat AD and vascular CIs are acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. It is expedient to use glutamatergic and acetylcholinergic therapy earlier in patients with obvious CIs that are unassociated with emotional problems and disturbance of consciousness. Akatinol memantine is a drug that can be regarded not only as a symptomatic but also pathogenetic agent. 

  14. Distinguishing between vascular dementia and Alzheimer's disease by means of the WAIS: a meta-analysis. (United States)

    Oosterman, Joukje M; Scherder, Erik J A


    This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests that require executive functions, whereas inferior performance of the Alzheimer's disease patients was expected on memory tests. Two steps in the analysis were undertaken in an attempt to clarify this issue. The first step consisted of including all studies examining Wechsler Adult Intelligence Scale subtest performance in vascular dementia and Alzheimer's disease patients. Secondly, a subcortical vascular dementia subgroup was distinguished and performance of this subgroup was compared to that of the Alzheimer's disease group.Overall, the analyses showed that both the vascular dementia and, more strongly, the subcortical vascular dementia group revealed decreased executive functions on several subtests compared to the Alzheimer's disease group. The Alzheimer's disease group showed inferior performance on a single semantic memory test only compared to both the vascular dementia and the subcortical vascular dementia groups. These results indicate that several subtests of the Wechsler Adult Intelligence Scale can differentiate between these two clinical groups, and that most of these tests reveal more impaired performance in the vascular dementia group.

  15. Biological markers of Alzheimer?s disease

    Directory of Open Access Journals (Sweden)

    Leonardo Cruz de Souza


    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.

  16. A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study

    NARCIS (Netherlands)

    R.J. Jutten (Roos); Harrison, J. (John); F.J. De Jong (Frank J.); A. Aleman (André); Ritchie, C.W. (Craig W.); P. Scheltens (Philip); Sikkes, S.A.M. (Sietske A.M.)


    markdownabstract__Introduction__ Cognitive testing in Alzheimer's disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments t

  17. Demência de alzheimer


    Galvão, Ana Maria


    A doença de Alzheimer é considerada a demência mais comum no ser humano, sendo caraterizada como um distúrbio degenerativo do cérebro que leva à perda de memória (Alzheimer's Association, 2010). A notícia de um diagnóstico de demência causa um intenso impacto na vida de pacientes e familiares. Os principais motivos referem-se à impossibilidade de cura e à progressão por vezes rápida dos sintomas. São comumente evidenciadas reações emocionais negativas envolvendo impotência, medo e...

  18. Botanics: a potential source of new therapies for Alzheimer's disease?

    Directory of Open Access Journals (Sweden)

    Syad AN


    Full Text Available Arif Nisha Syad, Kasi Pandima Devi Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India Abstract: Alzheimer's disease is an age-related, complex neurodegenerative disorder characterized by loss of memory and impairment of multiple cognitive functions. Several factors contribute to the progression and development of the disease including amyloid beta accumulation, neurofibrillary tangle formation, cholinergic deficit, oxidative stress, neuroinflammation, and apoptosis. Numerous traditional and herbal medicinal plants have been used to treat several cognitive disorders including Alzheimer's disease. They act as excellent antioxidants, anti-inflammatory mediators, and cholinesterase and β-secretase inhibitors. In addition, these natural compounds also prevent the accumulation of amyloid beta and its fibril formation. Besides acting as core-molecules, these natural compounds act as a template for the production and synthesis of several drug leads with improved pharmacokinetic potentials and greater efficacies. Hence, herbal medicines that have interesting pharmacological effects with noticeable anti-Alzheimer's potential deserve increased attention for further development to drug entities. The present article reviews the botanical pharmacology with special reference to anti-Alzheimer activity of plants and plant-derived compounds. Keywords: neurodegeneration, medicinal plants, antioxidants, Aβ peptide, neuroprotective, clinical trials


    Institute of Scientific and Technical Information of China (English)


    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.

  20. Therapeutics for Alzheimer's disease based on the metal hypothesis. (United States)

    Bush, Ashley I; Tanzi, Rudolph E


    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."

  1. Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes (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.


    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

  2. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ


    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. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG


    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

  4. Gene Therapy Strategies for Alzheimer's Disease: An Overview. (United States)

    Alves, Sandro; Fol, Romain; Cartier, Nathalie


    Key neuropathological hallmarks of Alzheimer's disease (AD) are extracellular amyloid plaques and intracellular accumulation of hyperphosphorylated Tau protein. The mechanisms underlying these neuropathological changes remain unclear. So far, research on AD therapy has had limited success in terms of symptomatic treatments although it has also had several failures for disease-modifying drugs. Gene transfer strategies to the brain have contributed to evaluate in animal models many interesting tracks, some of which should deserve clinical applications in AD patients in the future.

  5. mNos2 deletion and human NOS2 replacement in Alzheimer disease models. (United States)

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


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

  6. Contact Heat Evoked Potentials (CHEPs) in Patients with Mild-Moderate Alzheimer's Disease and Matched Control

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Madsen, Caspar Skau; Waldemar, Gunhild


    OBJECTIVE: Clinical studies have found that patients with Alzheimer's disease report pain of less intensity and with a lower affective response, which has been thought to be due to altered pain processing. The authors wished to examine the cerebral processing of non-painful and painful stimuli...... using somatosensory evoked potentials and contact heat evoked potentials in patients with Alzheimer's disease and in healthy elderly controls. DESIGN: Case-control study SETTING AND SUBJECTS: Twenty outpatients with mild-moderate Alzheimer's disease and in 17 age- and gender-matched healthy controls...... threshold and heat pain threshold. Somatosensory evoked potentials, amplitude, and latency were within normal range and similar for the two groups. CONCLUSIONS: The findings suggest that the processing of non-painful and painful stimuli is preserved in patients with mild to moderate Alzheimer's disease....

  7. Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Nielsen, J.E.; Stokholm, J.


    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...

  8. Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia. (United States)

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


    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.

  9. Clinical Study on Cluster Needling of Scalp Point Therapy for Depression Caused by Alzheimer's Disease%头穴丛刺对阿尔茨海默病所致抑郁的临床研究

    Institute of Scientific and Technical Information of China (English)

    卢琰琰; 黄东挺; 廖炼炼; 黄洪


    目的:探讨头穴丛刺针法对阿尔茨海默病所致抑郁的影响及康复疗效。方法:选取100例阿尔茨海默病至抑郁患者随机分为两组,对照组口服盐酸氟西汀,每日1次,治疗组在对照组基础上加用头穴丛刺针法进行治疗。两组分别于治疗前、2周、4周及8周后,采用汉密尔顿抑郁量表( HAMD)和AD评估量表认知分量表( ADAS-cog)进行康复效果评定,并进行统计学分析。结果:治疗组的各项评分均优于对照组,差异均有统计学意义( P<0.05)。结论:头穴丛刺针法可以较好地改善阿尔茨海默病患者临床抑郁症状,其康复疗效优于单纯服用西药治疗。%Objective:To investigate the cluster needling of scalp point therapy for depression caused by Alzhe-imer's disease and the efficacy of rehabilitation.Methods:100 cases of Alzheimer's disease inducing depression were randomly divided into two groups.Patients in the control group took fluoxetine hydrochloride orally, with once daily;the treatment group was based on the therapy in the control group and received cluster needling of scalp point treatment.Two groups before treatment, after treatment respectively two weeks, four weeks and eight weeks later we used Hamilton Depression scale ( HAMD) and Alzheimer's disease cognize scale to assess the rehabilitation scores and make a statistical analysis.Results:The treatment group was superior to the control group according to the scores,and the differences were statistically significant (P<0.05).Conclusion:Cluster needling of scalp point therapy can better improve the symptoms of depression caused by Alzheimer's disease, and the rehabilitation efficacy is superior to simply taking western medicine.

  10. Genome instability in Alzheimer disease

    DEFF Research Database (Denmark)

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


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

  11. Context memory in Alzheimer's disease

    NARCIS (Netherlands)

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


    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.

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  13. The role of inflammasome in Alzheimer's disease. (United States)

    Liu, Li; Chan, Christina


    Alzheimer's disease (AD) is a chronic, progressive and irreversible neurodegenerative disease with clinical characteristics of memory loss, dementia and cognitive impairment. Although the pathophysiologic mechanism is not fully understood, inflammation has been shown to play a critical role in the pathogenesis of AD. Inflammation in the central nervous system (CNS) is characterized by the activation of glial cells and release of proinflammatory cytokines and chemokines. Accumulating evidence demonstrates that inflammasomes, which cleave precursors of interleukin-1β (IL-1β) and IL-18 to generate their active forms, play an important role in the inflammatory response in the CNS and in AD pathogenesis. Therefore, modulating inflammasome complex assembly and activation could be a potential strategy for suppressing inflammation in the CNS. This review aims to provide insight into the role of inflammasomes in the CNS, with respect to the pathogenesis of AD, and may provide possible clues for devising novel therapeutic strategies.

  14. Disturbed Copper Bioavailability in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Daniela Kaden


    Full Text Available Recent data from in vitro, animal, and human studies have shed new light on the positive roles of copper in many aspects of AD. Copper promotes the non-amyloidogenic processing of APP and thereby lowers the Aβ production in cell culture systems, and it increases lifetime and decreases soluble amyloid production in APP transgenic mice. In a clinical trial with Alzheimer patients, the decline of Aβ levels in CSF, which is a diagnostic marker, is diminished in the verum group (8 mg copper/day, indicating a beneficial effect of the copper treatment. These observations are in line with the benefit of treatment with compounds aimed at normalizing metal levels in the brain, such as PBT2. The data reviewed here demonstrate that there is an apparent disturbance in metal homeostasis in AD. More research is urgently needed to understand how this disturbance can be addressed therapeutically.

  15. ABC Transporters and the Alzheimer's Disease Enigma. (United States)

    Wolf, Andrea; Bauer, Björn; Hartz, Anika M S


    Alzheimer's disease (AD) is considered the "disease of the twenty-first century." With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P-glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets.

  16. Chemokines in CSF of Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa


    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.

  17. Domain adaptation for Alzheimer's disease diagnostics. (United States)

    Wachinger, Christian; Reuter, Martin


    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.

  18. Alzheimer disease and pre-emptive suicide. (United States)

    Davis, Dena S


    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.

  19. Presentation and stability of noncognitive symptom patterns in patients with Alzheimer disease. (United States)

    Haupt, M; Jänner, M; Ebeling, S; Stierstorfer, A; Kretschmar, C


    The purpose of this study was to investigate noncognitive symptoms in Alzheimer disease to identify symptom patterns and to study stability of such patterns prospectively. Furthermore, variables were examined that could be associated with certain types of symptom patterns or could be predictors of change of these patterns. Forty-eight patients with the clinical diagnosis of probable Alzheimer disease were included in this study and were assessed weekly over a 3-week period. Noncognitive symptoms were rated according to the Behavioral Abnormalities in Alzheimer's Disease Rating Scale and the Dementia Mood Assessment Scale and to a set of items that specifically assess misidentifications. By means of principal component factor analysis different noncognitive symptom patterns were obtained, yielding a four-factor solution. They mapped onto rational domains with respect to clinical experience: depression, apathy, psychotic symptoms/aggression, and misidentifications/agitation. Demographic and clinical variables were not associated with the factor solutions and did not predict change of the factor values. The results demonstrate that in Alzheimer disease there are distinct noncognitive symptom patterns that hold at least short-term prospective stability. None of the examined clinical variables, such as age at entry, the status of the patients (outpatient or inpatient), or dementia severity, exerted substantial influence on the noncognitive symptom patterns. Further investigations should concentrate on the pathological and prognostic correlates of noncognitive symptom patterns in Alzheimer disease.

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

  1. 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


    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

  2. Imaging the earliest stages of Alzheimer's disease. (United States)

    Wu, William; Small, Scott A


    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.

  3. Relation between nicotine intake and Alzheimer's disease.



    OBJECTIVE--To study the association between Alzheimer's disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer's disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer's disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative ris...

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

    KAUST Repository

    Demetrius, Lloyd A.


    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.

  5. In vivo quantitative susceptibility mapping (QSM in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Julio Acosta-Cabronero

    Full Text Available BACKGROUND: This study explores the magnetostatic properties of the Alzheimer's disease brain using a recently proposed, magnetic resonance imaging, postprocessed contrast mechanism. Quantitative susceptibility mapping (QSM has the potential to monitor in vivo iron levels by reconstructing magnetic susceptibility sources from field perturbations. However, with phase data acquired at a single head orientation, the technique relies on several theoretical approximations and requires fast-evolving regularisation strategies. METHODS: In this context, the present study describes a complete methodological framework for magnetic susceptibility measurements with a review of its theoretical foundations. FINDINGS AND SIGNIFICANCE: The regional and whole-brain cross-sectional comparisons between Alzheimer's disease subjects and matched controls indicate that there may be significant magnetic susceptibility differences for deep brain nuclei--particularly the putamen--as well as for posterior grey and white matter regions. The methodology and findings described suggest that the QSM method is ready for larger-scale clinical studies.

  6. New Perspectives on Alzheimer's Disease and Nutrition. (United States)

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


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

  7. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease. (United States)

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


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

  8. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease. (United States)

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


    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.

  9. Special Issue: "Molecules against Alzheimer". (United States)

    Decker, Michael; Muñoz-Torrero, Diego


    This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue.

  10. The neurologic examination in patients with probable Alzheimer's disease. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Jacqueline Machado


    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

  12. Recent progress of PET in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Na NIU


    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

  13. Alzheimer's Disease: Symptoms, Diagnosis and Treatment (United States)

    ... page please turn Javascript on. Feature: Alzheimer's Disease Symptoms, Diagnosis and Treatment Past Issues / Fall 2010 Table of Contents Symptoms Scientists believe that changes in the brain may ...

  14. Structural connectivity of the default mode network and cognition in Alzheimer׳s disease. (United States)

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


    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.

  15. 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)


    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)

  16. Alzheimer's disease | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available eeks prior to randomization.• other N-methyl-D-aspartate (NMDA) antagonists: amantadine, ketamine, and dextromethorphan...ated or not recommended in combination with memantine, as defined in the British National Formulary, including ketamine, dextromethor...phan, amantidine.• Written informed consent provided by the participant’s next of k

  17. A data-driven model of biomarker changes in sporadic Alzheimer's disease. (United States)

    Young, Alexandra L; Oxtoby, Neil P; Daga, Pankaj; Cash, David M; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M; Alexander, Daniel C


    We demonstrate the use of a probabilistic generative model to explore the biomarker changes occurring as Alzheimer's disease develops and progresses. We enhanced the recently introduced event-based model for use with a multi-modal sporadic disease data set. This allows us to determine the sequence in which Alzheimer's disease biomarkers become abnormal without reliance on a priori clinical diagnostic information or explicit biomarker cut points. The model also characterizes the uncertainty in the ordering and provides a natural patient staging system. Two hundred and eighty-five subjects (92 cognitively normal, 129 mild cognitive impairment, 64 Alzheimer's disease) were selected from the Alzheimer's Disease Neuroimaging Initiative with measurements of 14 Alzheimer's disease-related biomarkers including cerebrospinal fluid proteins, regional magnetic resonance imaging brain volume and rates of atrophy measures, and cognitive test scores. We used the event-based model to determine the sequence of biomarker abnormality and its uncertainty in various population subgroups. We used patient stages assigned by the event-based model to discriminate cognitively normal subjects from those with Alzheimer's disease, and predict conversion from mild cognitive impairment to Alzheimer's disease and cognitively normal to mild cognitive impairment. The model predicts that cerebrospinal fluid levels become abnormal first, followed by rates of atrophy, then cognitive test scores, and finally regional brain volumes. In amyloid-positive (cerebrospinal fluid amyloid-β1-42 Alzheimer's disease subjects (maximum classification accuracy of 99%), and predicts conversion from mild cognitive impairment to Alzheimer's disease (maximum balanced accuracy of 77% over 3 years), and from cognitively normal to mild cognitive impairment (maximum balanced accuracy of 76% over 5 years). By fitting Cox proportional hazards models, we find that baseline model stage is a significant risk factor for

  18. Drugs of Alzheimer's disease targeting amyloid beta-peptide in phase Ⅲ clinical trials%进入临床试验Ⅲ期以β淀粉样蛋白为靶标的抗阿尔采末病药物

    Institute of Scientific and Technical Information of China (English)

    史长城; 于锋


    Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder. To date, there is still no effective drug for it. With more understanding about the etiology and pathogenesis of AD, amyloid beta - peptide (Aβ) is considered to be an important factor. Therefore, results of these clinical trials with many drugs targeting Aβ were disappointed. Clinical trials of two drugs, tramiprosate and semagacestat have been terminated. The paper reviewed these drugs targeting Aβ in phase Ⅲ clinical trials, in order to provide reference services to researchers.%阿尔采末病(AD)是一种常见的神经退行性疾病,目前尚无有效的治疗药物.随着AD发病机制研究的深入,β淀粉样蛋白(amyloid beta-peptide,Aβ)被认为是AD发病重要因素之一.因此,很多药物设计选择以Aβ为靶标,但这类药物的临床研究却受到不同程度的挫折,tram1prosate和semagacestat的临床试验已经提前终止.本文对目前进入临床试验Ⅲ期以Aβ为靶标的药物进行综述,以期为研究者提供参考.

  19. 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


    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.

  20. Connected speech as a marker of disease progression in autopsy-proven Alzheimer's disease. (United States)

    Ahmed, Samrah; Haigh, Anne-Marie F; de Jager, Celeste A; Garrard, Peter


    Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer's disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer's disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer's disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer's disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer's disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer's disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer's disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the

  1. 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


    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

  2. Alzheimer's disease drug development: translational neuroscience strategies. (United States)

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


    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.

  3. Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease. (United States)

    Gonsalvez, Irene; Baror, Roey; Fried, Peter; Santarnecchi, Emiliano; Pascual-Leone, Alvaro


    Alzheimer's disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neurological and psychiatric conditions. The aim of this review is summarize data from therapeutic trials of NBS in AD and other dementing illnesses. Despite the potential of NBS, there is limited theoretical framework and a lack of guidelines for its applications to AD. Several published clinical trials failed to report key parameters of the interventions thus limiting the utility of the study to assess efficacy and safety. Our review concludes with some suggestions for future studies aimed to advance research into NBS as a potential treatment for the symptoms and disabilities caused by AD and to enable comparison of results across trials. Ultimately, appropriately powered, and controlled, multi-site randomized clinical trials will be needed to evaluate the therapeutic potential of NBS in AD.

  4. Toward precision medicine in Alzheimer's disease. (United States)

    Reitz, Christiane


    In Western societies, Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death. In recent years, the concept of precision medicine, an approach for disease prevention and treatment that is personalized to an individual's specific pattern of genetic variability, environment and lifestyle factors, has emerged. While for some diseases, in particular select cancers and a few monogenetic disorders such as cystic fibrosis, significant advances in precision medicine have been made over the past years, for most other diseases precision medicine is only in its beginning. To advance the application of precision medicine to a wider spectrum of disorders, governments around the world are starting to launch Precision Medicine Initiatives, major efforts to generate the extensive scientific knowledge needed to integrate the model of precision medicine into every day clinical practice. In this article we summarize the state of precision medicine in AD, review major obstacles in its development, and discuss its benefits in this highly prevalent, clinically and pathologically complex disease.

  5. Spatial Navigation in Preclinical Alzheimer's Disease (United States)

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


    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

  6. Turning principles into practice in Alzheimer's disease

    NARCIS (Netherlands)

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


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

  7. Gaps in Alzheimer's Knowledge among College Students (United States)

    Eshbaugh, Elaine M.


    Despite the prevalence of the disease, it appears that there may be a need for increased education for formal and family caregivers of those with Alzheimer's disease and related dementias. Today's college students will be asked to fill both of these roles in the future. This study examined the level of knowledge of Alzheimer's disease among…

  8. Fatty acids, lipid metabolism and Alzheimer pathology.

    NARCIS (Netherlands)

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


    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

  9. Sinp 2012: Alzheimer, aggiornamenti dalla ricerca

    Directory of Open Access Journals (Sweden)

    Giulia Canali


    Full Text Available Al congresso Sinp 2012 svoltosi a Roma a Novembre, E. Ferrari e colleghi hanno presentato uno studio sulla percezione sociale nella malattia di Alzheimer (AD e nella demenza lobare frontotemporale (DLFT. Dal canto loro L. Serra e colleghi hanno messo in luce i correlati neuroanatomici della aprassia costruttiva nei pazienti con Alzheimer.

  10. Alzheimer's Disease - Multiple Languages: MedlinePlus (United States)

    ... d'Alzheimer - français (French) Bilingual PDF Health Information Translations Inside the Brain: An Interactive Tour English Exploration Interactive de l'Intérieur du Cerveau - français (French) Alzheimer's Association German (Deutsch) Inside the Brain: An Interactive Tour English Im ...

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


    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


    Directory of Open Access Journals (Sweden)

    Ana Comesaña


    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.

  13. Insight into the Molecular Imaging of Alzheimer's Disease (United States)

    Bhagat, Neeta


    Alzheimer's disease is a complex neurodegenerative disease affecting millions of individuals worldwide. Earlier it was diagnosed only via clinical assessments and confirmed by postmortem brain histopathology. The development of validated biomarkers for Alzheimer's disease has given impetus to improve diagnostics and accelerate the development of new therapies. Functional imaging like positron emission tomography (PET), single photon emission computed tomography (SPECT), functional magnetic resonance imaging (fMRI), and proton magnetic resonance spectroscopy provides a means of detecting and characterising the regional changes in brain blood flow, metabolism, and receptor binding sites that are associated with Alzheimer's disease. Multimodal neuroimaging techniques have indicated changes in brain structure and metabolic activity, and an array of neurochemical variations that are associated with neurodegenerative diseases. Radiotracer-based PET and SPECT potentially provide sensitive, accurate methods for the early detection of disease. This paper presents a review of neuroimaging modalities like PET, SPECT, and selected imaging biomarkers/tracers used for the early diagnosis of AD. Neuroimaging with such biomarkers and tracers could achieve a much higher diagnostic accuracy for AD and related disorders in the future. PMID:26880871

  14. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs]. (United States)

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


    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.

  15. Role of melatonin in Alzheimer-like neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Jian-zhi WANG; Ze-fen WANG


    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.

  16. The Importance of Adipokines in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seyid Ahmet Ay


    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

  17. Cohort profile: the Finnish Medication and Alzheimer's disease (MEDALZ) study (United States)

    Tolppanen, Anna-Maija; Taipale, Heidi; Koponen, Marjaana; Lavikainen, Piia; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa


    Purpose The aim of the Medicine use and Alzheimer's disease (MEDALZ) study is to investigate the changes in medication and healthcare service use among persons with Alzheimer's disease (AD) and to evaluate the safety and effectiveness of medications in this group. This is important, because the number of persons with AD is rapidly growing and even though they are a particularly vulnerable patient group, the number of representative, large-scale studies with adequate follow-up time is limited. Participants MEDALZ contains all residents of Finland who received a clinically verified diagnosis of AD between 2005 and 2011 and were community-dwelling at the time of diagnosis (N=70 719). The diagnosis is based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA) and Diagnostic and Statistical Manual Fourth Edition (DSM-IV) criteria for Alzheimer's disease. The cohort contains socioeconomic data (education, occupational status and taxable income, 1972–2012) and causes of death (2005–2012), data from the prescription register (1995–2012), the special reimbursement register (1972–2012) and the hospital discharge register (1972–2012). Future updates are planned. The average age was 80.1 years (range 34.5–104.6 years). The majority of cohort (65.2%) was women. Currently, the average length of follow-up after AD diagnosis is 3.1 years and altogether 26 045 (36.8%) persons have died during the follow-up. Findings Altogether 53% of the cohort had used psychotropic drugs within 1 year after AD diagnoses. The initiation rate of for example, benzodiazepines and related drugs and antidepressants began to increase already before AD diagnosis. Future plans We are currently assessing if these, and other commonly used medications are related to adverse events such as death, hip fractures, head injuries and pneumonia. PMID:27412109

  18. Cellular basis of Alzheimer's disease. (United States)

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence


    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  19. 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.


    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)

  20. Preclinical Alzheimer disease —the challenges ahead (United States)

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


    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

  1. Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging. (United States)

    Hamelin, Lorraine; Lagarde, Julien; Dorothée, Guillaume; Leroy, Claire; Labit, Mickael; Comley, Robert A; de Souza, Leonardo Cruz; Corne, Helene; Dauphinot, Luce; Bertoux, Maxime; Dubois, Bruno; Gervais, Philippe; Colliot, Olivier; Potier, Marie Claude; Bottlaender, Michel; Sarazin, Marie


    While emerging evidence suggests that neuroinflammation plays a crucial role in Alzheimer's disease, the impact of the microglia response in Alzheimer's disease remains a matter of debate. We aimed to study microglial activation in early Alzheimer's disease and its impact on clinical progression using a second-generation 18-kDa translocator protein positron emission tomography radiotracer together with amyloid imaging using Pittsburgh compound B positron emission tomography. We enrolled 96 subjects, 64 patients with Alzheimer's disease and 32 controls, from the IMABio3 study, who had both (11)C-Pittsburgh compound B and (18)F-DPA-714 positron emission tomography imaging. Patients with Alzheimer's disease were classified as prodromal Alzheimer's disease (n = 38) and Alzheimer's disease dementia (n = 26). Translocator protein-binding was measured using a simple ratio method with cerebellar grey matter as reference tissue, taking into account regional atrophy. Images were analysed at the regional (volume of interest) and at the voxel level. Translocator protein genotyping allowed the classification of all subjects in high, mixed and low affinity binders. Thirty high+mixed affinity binders patients with Alzheimer's disease were dichotomized into slow decliners (n = 10) or fast decliners (n = 20) after 2 years of follow-up. All patients with Alzheimer's disease had an amyloid positive Pittsburgh compound B positron emission tomography. Among controls, eight had positive amyloid scans (n = 6 high+mixed affinity binders), defined as amyloidosis controls, and were analysed separately. By both volumes of interest and voxel-wise comparison, 18-kDa translocator protein-binding was higher in high affinity binders, mixed affinity binders and high+mixed affinity binders Alzheimer's disease groups compared to controls, especially at the prodromal stage, involving the temporo-parietal cortex. Translocator protein-binding was positively correlated with Mini-Mental State Examination

  2. Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease. (United States)

    Shinohara, Mitsuru; Fujioka, Shinsuke; Murray, Melissa E; Wojtas, Aleksandra; Baker, Matthew; Rovelet-Lecrux, Anne; Rademakers, Rosa; Das, Pritam; Parisi, Joseph E; Graff-Radford, Neill R; Petersen, Ronald C; Dickson, Dennis W; Bu, Guojun


    regional distribution of APP as well as β-C-terminal fragment of APP were strongly associated with the regional pattern of amyloid-β₄₂ accumulation in familial Alzheimer's disease. Apolipoprotein E and GFAP showed negative regional association with amyloid-β (especially amyloid-β₄₀) accumulation in both sporadic and familial Alzheimer's disease. Familial Alzheimer's disease had greater striatal tau pathology than sporadic Alzheimer's disease. In a retrospective medical record review, atypical signs and symptoms were more frequent in familial Alzheimer's disease compared with sporadic Alzheimer's disease. These results suggest that disproportionate amyloid-β₄₂ accumulation in cortical areas in sporadic Alzheimer's disease may be mediated by synaptic processes, whereas disproportionate amyloid-β₄₂ accumulation in subcortical areas in familial Alzheimer's disease may be driven by APP and its processing. Region-specific amyloid-β₄₂ accumulation might account for differences in the relative amounts of tau pathology and clinical symptoms in familial and sporadic Alzheimer's disease.

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

    DEFF Research Database (Denmark)

    Waldemar, G; Bruhn, P; Schmidt, E


    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...

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


    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…

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

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta


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

  6. 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.


    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 sam...

  7. 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


    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

  8. 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)


    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

  9. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update

    NARCIS (Netherlands)

    Del Campo, M.; Mollenhauer, B.; Bertolotto, A.; Engelborghs, S.; Hampel, H.; Simonsen, A.H.; Kapaki, E.; Kruse, N.; Bastard, N. le; Lehmann, S.; Molinuevo, J.L.; Parnetti, L.; Perret-Liaudet, A.; Saez-Valero, J.; Saka, E.; Urbani, A.; Vanmechelen, E.; Verbeek, M.M.; Visser, P.J.; Teunissen, C.


    Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging du

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

    Directory of Open Access Journals (Sweden)

    Orestes V. Forlenza


    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

  11. 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


    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.

  12. 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

    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.

  13. Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation? (United States)

    Mantovani, E; Costa, I P; Gauditano, G; Bonoldi, V L N; Higuchi, M L; Yoshinari, N H


    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.

  14. [BACE1 inhibitors for the treatment of Alzheimer disease]. (United States)

    Tomita, Taisuke


    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.

  15. Dementia in the movies: the clinical picture

    NARCIS (Netherlands)

    Gerritsen, D.; Kuin, Y.; Nijboer, J.


    Objectives: Visual media influence the general public's perceptions and attitudes regarding people with mental conditions. This qualitative study investigates the depiction accuracy of dementia's clinical features in motion pictures.Method: Using the search terms dementia', Alzheimer's disease' and

  16. Dementia in the movies: The clinical picture

    NARCIS (Netherlands)

    Gerritsen, D.L.; Kuin, Y.; Nijboer, J.


    Objectives: Visual media influence the general public's perceptions and attitudes regarding people with mental conditions. This qualitative study investigates the depiction accuracy of dementia's clinical features in motion pictures.Method: Using the search terms 'dementia', 'Alzheimer's disease' an

  17. 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)


    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.

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

    Directory of Open Access Journals (Sweden)

    Zella Davide


    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.

  19. Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: Role of quercetin


    Dilip Dodda; Ruchi Chhajed; Jitendriya Mishra; Monalisa Padhy


    Objective: This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats. Materials and Methods: Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), contro...

  20. Targeting synaptic dysfunction in Alzheimer's disease therapy. (United States)

    Nisticò, Robert; Pignatelli, Marco; Piccinin, Sonia; Mercuri, Nicola B; Collingridge, Graham


    In the past years, major efforts have been made to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been translated into extensive experimental approaches aimed at slowing down or halting disease progression. Advances in transgenic (Tg) technologies allowed the engineering of different mouse models of AD recapitulating a range of AD-like features. These Tg models provided excellent opportunities to analyze the bases for the temporal evolution of the disease. Several lines of evidence point to synaptic dysfunction as a cause of AD and that synapse loss is a pathological correlate associated with cognitive decline. Therefore, the phenotypic characterization of these animals has included electrophysiological studies to analyze hippocampal synaptic transmission and long-term potentiation, a widely recognized cellular model for learning and memory. Transgenic mice, along with non-Tg models derived mainly from exogenous application of Aβ, have also been useful experimental tools to test the various therapeutic approaches. As a result, numerous pharmacological interventions have been reported to attenuate synaptic dysfunction and improve behavior in the different AD models. To date, however, very few of these findings have resulted in target validation or successful translation into disease-modifying compounds in humans. Here, we will briefly review the synaptic alterations across the different animal models and we will recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. Finally, we will highlight intrinsic limitations in the use of experimental systems and related challenges in translating preclinical studies into human clinical trials.

  1. Explorative and targeted neuroproteomics in Alzheimer's disease. (United States)

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


    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.

  2. Does insulin therapy for type 1 diabetes mellitus protect against Alzheimer's disease? (United States)

    Rdzak, Grzegorz M; Abdelghany, Osama


    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.

  3. A test of lens opacity as an indicator of preclinical Alzheimer Disease. (United States)

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


    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.

  4. Peripheral Vitamin C Levels in Alzheimer's Disease: A Cross-Sectional Study. (United States)

    Ide, Kazuki; Yamada, Hiroshi; Kawasaki, Yohei; Yamanaka, Mie; Kawakami, Nobuko; Katsuyama, Yusuke; Yoshida, Hidefumi; Kim, Kang; Shiosaki, Emi; Sonoda, Akihiro; Umegaki, Keizo; Harada, Kiyoshi


    We previously reported lower lymphocyte vitamin C levels in individuals with type 2 diabetes mellitus and in individuals with severe Parkinson's disease. Oxidative stress has been proposed to play a key role in the progression of Alzheimer's disease. Thus, the objective of this study was to investigate the association between peripheral levels of vitamin C and the progression of cognitive dysfunction in Alzheimer's disease. Fifty individuals with Alzheimer's disease being treated at Shizuoka General Hospital were consecutively enrolled in this study from December 2009 to March 2015 (76.0±9.7 y of age [mean±SD]; 32 men and 18 women; Mini-Mental State Examination Japanese version (MMSE-J) score range, 8-27). Plasma and lymphocyte vitamin C levels in fasting blood samples were measured. The association between the MMSE-J scores and vitamin C levels was estimated using Spearman's rank correlation coefficient (ρ) and the criteria defined by Swinscow. Spearman's ρ for the relationship between peripheral vitamin C levels and the MMSE-J score was ρ=0.17 for plasma vitamin C and ρ=0.26 for lymphocyte vitamin C. Thus, the associations were relatively weak based on the criteria. In contrast with type 2 diabetes mellitus and Parkinson's disease, lymphocyte vitamin C levels in the peripheral blood may not directly reflect the progression of cognitive dysfunction in Alzheimer's disease. Additional longitudinal studies are needed to evaluate the clinical importance of changes of peripheral vitamin C status in Alzheimer's disease.

  5. BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease. (United States)

    Lim, Yen Ying; Hassenstab, Jason; Cruchaga, Carlos; Goate, Alison; Fagan, Anne M; Benzinger, Tammie L S; Maruff, Paul; Snyder, Peter J; Masters, Colin L; Allegri, Ricardo; Chhatwal, Jasmeer; Farlow, Martin R; Graff-Radford, Neill R; Laske, Christoph; Levin, Johannes; McDade, Eric; Ringman, John M; Rossor, Martin; Salloway, Stephen; Schofield, Peter R; Holtzman, David M; Morris, John C; Bateman, Randall J


    SEE ROGAEVA AND SCHMITT-ULMS DOI101093/AWW201 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ε4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val66 homozygotes, 48 Met66 carriers). Among preclinical mutation carriers, Met66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val66 homozygotes. Cortical amyloid-β and cerebrospinal fluid amyloid-β42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val66 homozygotes and Met66 carriers. There was an effect of APOE on amyloid-β levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-β on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-β in autosomal dominant Alzheimer's disease.

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

    Directory of Open Access Journals (Sweden)

    Licastro Federico


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

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

    Directory of Open Access Journals (Sweden)

    Enrico Mossello


    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.

  8. Education and the risk for Alzheimer's disease

    DEFF Research Database (Denmark)

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


    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...

  9. Lithium May Fend off Alzheimer's Disease

    Institute of Scientific and Technical Information of China (English)

    Helen Pilcher; 夏红


    @@ 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.

  10. Alzheimer's and Dementia Testing for Earlier Diagnosis (United States)

    ... Today Major Milestones Treatment Horizon Earlier Diagnosis Prevention Alzheimer’s and Dementia Testing for Earlier Diagnosis What if we could diagnose Alzheimer's before symptoms started? The hope is, future treatments ...

  11. 2016 Alzheimer's disease facts and figures. (United States)


    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

  12. Fisher Center for Alzheimer's Research Foundation (United States)

    ... a Cure Read More Together we can make Alzheimer's nothing but a memory Scroll to see how ... cure We are making a major impact on Alzheimer’s research. Our scientific discoveries are featured in top ...

  13. Can Air Pollution Heighten Alzheimer's Risk? (United States)

    ... Can Air Pollution Heighten Alzheimer's Risk? Fine particles from power plants ... 1, 2017 WEDNESDAY, Feb. 1, 2017 (HealthDay News) -- Air pollution may cause more than just lung disease: New ...

  14. APP processing in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Zhang Yun-wu


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

  15. Lipofuscin hypothesis of Alzheimer's disease. (United States)

    Giaccone, Giorgio; Orsi, Laura; Cupidi, Chiara; Tagliavini, Fabrizio


    The primary culprit responsible for Alzheimer's disease (AD) remains unknown. Aβ protein has been identified as the main component of amyloid of senile plaques, the hallmark lesion of AD, but it is not definitively established whether the formation of extracellular Aβ deposits is the absolute harbinger of the series of pathological events that hit the brain in the course of sporadic AD. The aim of this paper is to draw attention to a relatively overlooked age-related product, lipofuscin, and advance the hypothesis that its release into the extracellular space following the death of neurons may substantially contribute to the formation of senile plaques. The presence of intraneuronal Aβ, similarities between AD and age-related macular degeneration, and the possible explanation of some of the unknown issues in AD suggest that this hypothesis should not be discarded out of hand.

  16. Brain Imaging in Alzheimer Disease (United States)

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


    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

  17. Circulating Biomarker Panels in Alzheimer's Disease. (United States)

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


    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.

  18. Biomarkers in Alzheimer's Disease-Recent Update. (United States)

    Sharma, Sushil; Lipincott, Walter


    Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage. Biomarker(s) with high sensitivity and specificity would facilitate AD diagnosis at early stages. Currently, CSF amyloid β 1-42, total tau, and phosphorylated tau181 are used as AD biomarkers. This report describes conventional and potential in-vitro and in-vivo biomarkers of AD. Particularly, in-vitro transcriptomic, proteomic, lipidomic, and metabolomic; body fluid biomarkers (C-reactive proteins, homocysteine, α-sunuclein index, and dehydroepiandrosterone sulphate) from blood, serum, plasma, CSF, and saliva; and neuronal, platelets, and lymphocyte microRNA, mtDNA, and Charnoly body are detected. In-vivo physiological and neurobehavioral biomarkers are evaluated by analyzing computerized EEG, event-related potentials, circadian rhythm, and multimodality fusion imaging including: CT, MRI, SPECT, and PET. More specifically, PET imaging biomarkers representing reduced fronto-temporal 18FdG uptake, increased 11C or 18F-PIB uptake, 11C-PBR28 to measure 18 kDa translocator protein (TSPO), a biomarker for inflammation; and 3-D MRI (ventriculomegaly)/MRS are performed for early and effective clinical management of AD.

  19. Advances in the study of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Angue Nkoghe Francoise; Yunman Li


    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.

  20. Does prevention for Alzheimer's disease exist?


    Sonia Maria Dozzi Brucki


    Abstract The prevention of Alzheimer's disease is a growing public health concern amidst an ageing population. Meanwhile, there is no effective or curative treatment available where prevention could greatly reduce health costs. This review was based on reports of potential preventive factors, including modifiable lifestyle factors, as well as preventive pharmacological strategies. Although the present review was not systematic, the reports selected from PubMed using "Alzheimer's disease" and ...

  1. The economic costs of Alzheimer's disease. (United States)

    Hay, J W; Ernst, R L


    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.

  2. Ferric cycle activity and Alzheimer disease. (United States)

    Dwyer, Barney E; Takeda, Atsushi; Zhu, Xiongwei; Perry, George; Smith, Mark A


    Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.

  3. 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.

  4. Periodontitis and Cognitive Decline in Alzheimer's Disease. (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


    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.

  5. Estrógenos, envejecimiento y enfermedad de Alzheimer Estrogens, aging and Alzheimer's dosiase

    Directory of Open Access Journals (Sweden)

    Fabio Sánchez E.


    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

  6. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies. (United States)

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


    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.

  7. Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders. (United States)

    Cai, Huan; Cong, Wei-na; Ji, Sunggoan; Rothman, Sarah; Maudsley, Stuart; Martin, Bronwen


    Alzheimer's disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer's disease, Huntington's disease, and Parkinson's disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies.

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

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    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.

  9. Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

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    François-B. Vialatte


    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.

  10. Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways (United States)

    Hof, P. R.; Vogt, B. A.; Bouras, C.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)


    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.

  11. Frontal variant of Alzheimer's disease and typical Alzheimer's disease: a comparative study

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    Bernardino Fernández-Calvo


    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.

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

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


    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: Sev...

  13. Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal Nonsteroidal Anti-Inflammatory Drugs? (United States)

    Lehrer, Steven; Rheinstein, Peter H


    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally.

  14. Progressive cholinergic decline in Alzheimer's Disease: consideration for treatment with donepezil 23 mg in patients with moderate to severe symptomatology

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    Cummings Jeffrey


    Full Text Available Abstract Of the estimated 5.3 million people with Alzheimer's disease in the United States, more than half would be classified as having moderate or severe disease. Alzheimer's disease is a progressive disorder with the moderate to severe stages generally characterized by significant cognitive, functional, and behavioral dysfunction. Unsurprisingly, these advanced stages are often the most challenging for both patients and their caregivers/families. Symptomatic treatments for moderate to severe Alzheimer's disease are approved in the United States and include the acetylcholinesterase inhibitor donepezil and the glutamate receptor antagonist memantine. Progressive symptomatic decline is nevertheless inevitable even with the available therapies, and therefore additional treatment options are urgently needed for this segment of the Alzheimer's disease population. An immediate-release formulation of donepezil has been available at an approved dose of 5-10 mg/d for the past decade. Recently, the United States Food and Drug Administration approved a higher-dose (23 mg/d donepezil formulation, which provides more gradual systemic absorption, a longer time to maximum concentration (8 hours versus the immediate-release formulation (3 hours, and higher daily concentrations. Herein, we review (1 the scientific data on the importance of cholinergic deficits in Alzheimer's disease treatment strategies, (2 the rationale for the use of higher-dose acetylcholinesterase inhibitors in patients with advanced disease, and (3 recent clinical evidence supporting the use of higher-dose donepezil in patients with moderate to severe Alzheimer's disease.

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

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    Tjaard U. Hoogenraad


    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.

  16. Common Alzheimer's Disease Research Ontology: National Institute on Aging and Alzheimer's Association collaborative project. (United States)

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


    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.

  17. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

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    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.


    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  18. Effect of Huanglian Jiedu Decoction on pitavastatin treatment of Alzheimer's disease

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    Hong-Lin Chen; Fang Guan


    Objective:To explore the effect of Huanglian Jiedu Decoction on pitavastatin treatment of Alzheimer's disease.Methods:A total of 200 cases of Alzheimer's disease of our department and department of geriatrics medicine of Harbin fifth hospital were selected, patients were divided into observation group and control group according to the random number table method by half. The control group was treated with pitavastatin, and the observation group was given the Huanglian Jiedu Decoction based on the control group. Before and after treatment, levels of cerebrospinal fluid Aβ-1-42 protein, phosphorylated tau protein, inflammation related factors IL-1β, IL-6, TNF-α, liver and renal function indexes of the two group patients with Alzheimer's disease were detected.Results:Compared with before treatment, levels of cerebrospinal fluid Aβ-1-42 protein and phosphorylated tau protein of the two groups were significantly decreased after treatment (P<0.05); after treatment, levels of cerebrospinal fluid Aβ-1-42 protein and phosphorylated tau protein of the observation group were significantly lower than those of the control group, (P<0.05); compared with before treatment, levels of inflammation related factors IL-1β, IL-6 and TNF-α of the two groups were significantly decreased after treatment (P<0.05); compared with the control group after treatment, after medication, levels of inflammation related factors IL-1β, IL-6 and TNF-α of the observation group were significantly decreased (P<0.05); compared with the control group after treatment, after combined treatment, levels of liver and renal function indexes of the observation group were significantly decreased (P<0.05).Conclusions:Huanglian Jiedu Decoction can decrease the level of inflammatory factors in patients with Alzheimer's disease, while reduce toxic side-effects of pitavastatin, and improve treatment efficiency of pitavastatin on Alzheimer's disease, which is of important clinical significance to improve

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

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    Luciane F. Viola


    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. Alzheimer neuropathology in non-Down's syndrome mentally retarded adults. (United States)

    Popovitch, E R; Wisniewski, H M; Barcikowska, M; Silverman, W; Bancher, C; Sersen, E; Wen, G Y


    We examined the brains of 385 mentally retarded adults aged 23-90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended age-specific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097-1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm2 consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Novel potential for the management of Alzheimer disease. (United States)

    Ginter, E; Simko, V; Weinrebova, D; Ladecka, Z


    Pathologic characteristics of Alzheimer disease (AD) are β-amyloid (Aβ) plaques, neurofibrillary tangles (NFT) and neurodegeneration. Currently, there is no cure for AD. Cilostazol, a selective inhibitor of type 3 phosphodiesterase, is likely to be a promising agent for AD. In the brain of the experimental animals it significantly reduced the Aβ amyloid plaques. Initial clinical reports on the effect of Cilostazol in AD patients are promising. In mice, stem cells favourably influence the pathogenetic process critical in AD, by reducing deposits of Aβ plaques. Clinical trials of the drug, called Betablock, are already underway in Britain. Successful management and resolution of AD in man will still require further intensive research (Fig. 4, Ref. 11).

  2. Bilingual People May Have an Edge Against Alzheimer's (United States)

    ... html Bilingual People May Have an Edge Against Alzheimer's Study found they did better on memory tests ... more languages appear to weather the ravages of Alzheimer's disease better than people who have only mastered ...

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

  4. Poor Sense of Smell May Signal Alzheimer's Risk (United States)

    ... 162068.html Poor Sense of Smell May Signal Alzheimer's Risk Testing looks for decreased olfactory sense, combined ... of smell may help predict their risk for Alzheimer's disease, a new study suggests. The researchers included ...

  5. Alzheimer's Protein Plaques May Also Harm the Heart (United States)

    ... page: Alzheimer's Protein Plaques May Also Harm the Heart Deposits ... fragments that form plaques in the brains of Alzheimer's patients might also stiffen their heart muscle and ...

  6. Test Predicting Alzheimer's Would Be Welcome, Survey Finds (United States)

    ... Test Predicting Alzheimer's Would Be Welcome, Survey Finds 3 out of ... could tell them they were going to develop Alzheimer's disease, most American seniors would take it, a ...

  7. Healthy Diet, Exercise May Help Keep Alzheimer's At Bay (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 ...

  8. Alzheimer's Patients' Use of Painkilling Patches Cause for Concern (United States)

    ... page: Alzheimer's Patients' Use of Painkilling Patches Cause for Concern ... of powerful opioid painkillers may be common among Alzheimer's disease patients and could be a cause for ...

  9. ANÁLISIS DEL DESEMPEÑO DEL LENGUAJE EN SUJETOS CON DEMENCIA TIPO ALZHEIMER (DTA Analysis of the language performance in subjects with Alzheimer type dementia (ATD

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    Catalina Malagón M


    Full Text Available Antecedentes: la demencia tipo Alzheimer representa un 50-70% de las enfermedades demenciales. Su prevalencia es del 3-5% en personas mayores de 65 años y su incidencia de 1-2% al año en la población general; se caracteriza por alteraciones progresivas en la memoria, el lenguaje, la atención, el comportamiento y la presencia de déficit visoespaciales. Objetivo: hacer un análisis descriptivo-comparativo de una muestra poblacional con demencia tipo Alzheimer, en especial una descripción fenomenológica de las alteraciones del lenguaje presentes en esa población. Métodos: como criterios de inclusión se usaron: diagnóstico de demencia tipo Alzheimer, dominancia manual derecha, escolaridad superior a quinto de primaria y capacidad para rendir las pruebas propuestas. Se comparó el rendimiento en las subpruebas de lenguaje del examen mínimo del estado mental (MMSE; en denominación y fluidez semántica y fonológica y se analizó el deterioro lingüístico en dos estadios de la demencia tipo Alzheimer. Resultados: en el estadio leve se evidencian déficit ligeros en todas las pruebas. Sin embargo los dominios con rendimiento más bajo fueron la fluidez fonológica y semántica. En el estadio moderado se evidenciaron diferencias en el rendimiento;las tareas de denominación, fluidez semántica y fluidez fonológica tuvieron rendimiento más bajo. Conclusiones: el lenguaje es un dominio que suele comprometerse en la demencia tipo Alzheimer. Los resultados reflejan el deterioro progresivo de la habilidad lingüística, manifiesto en un amplio rango de frecuencia entre el estadio leve y el moderado de la demencia. Existe un perfil similar de deterioro para los estadios leve y moderado con patrones independientes en las pruebas específicas.Background: Alzheimer disease explains near 70% of all instances of dementia and its prevalence in 65 years old population is 3-5% while incidence is near 1-2 % per year in general population. The clinical

  10. The Search for Biomarkers in Alzheimer's Disease

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    Anna Meiliana


    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.

  11. Biomedicine and Informatics Model of Alzheimer's Disease

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    Kang Cheng


    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

  12. Ethical issues in Alzheimer's disease: an overview. (United States)

    Leuzy, Antoine; Gauthier, Serge


    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.

  13. Desintegración de las praxias en la enfermedad de Alzheimer Disintegration of praxias in Alzheimer's disease: a case report

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    Carlos A. Bardeci


    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

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

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    Gross Hyman


    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

  15. Clinical study of deep brain magnetic stimulation technique in the treatment of Alzheimer's disease%深部脑磁刺激技术治疗阿尔茨海默病的临床研究

    Institute of Scientific and Technical Information of China (English)

    彭丹涛; 朱瑞; 袁欣瑞; 张筱


    Objective To explore the effectiveness and safety of deep brain magnetic stimulation technique (dTMS) for treatment of Alzheimer's disease (AD).Methods Totally 116 patients with AD were randomly divided into 4 groups:(1) dTMS:given dTMS really stimulation therapy,(2)medication group:treatment with donepezil 5 mg/d,(3) combination treatment group:given dTMS and donepezil therapy,(4) blank control group:given pseudorandom stimulation treatment.33 healthy control cases were given dTMS's stimulation treatment.The treatment course was 6 months.Application of mini mental state examination scale (MMSE),the Montreal cognitive assessment scale (MoCA),Hamilton Depression Scale (HAMD),ischemic scale (HIS),Boston naming test,activity of daily living(ADL) and neuropsychological questionnaire (NPI) were used to evaluate the cognitive function.All the participants received blood tests and ECG in order to evaluate the safety of dTMS.Results After 6 months treatment,compair with the blank control group,all scale scoresof dTMS group,medication group and combined treatment group were improved significantly in MMSE (t=2.49,2.46,2.20),MoCA(t=2.59,2.39,2.87),ADL(t=2.35,2.17,2.83),NPI(t=3.05,2.40,2.65) and sub-cognitive scale score (all P<0.05).All scale scores of combination treatment group were better than dTMS group and medication group (P<0.05).There's no significant difference between drug treatment groups and dTMS group (P>0.05).After 6 months treatment,compared with healthy control group,the scale scores were aggravated in 4 groups of AD (P<0.05)Conclusions dTMS can be effective and safe in the treatment of AD patients with cognitive and noncognitive symptoms.%目的 探讨深部脑磁刺激技术(dTMS)治疗阿尔茨海默病患者(AD)的有效性及安全性. 方法 AD患者116例和年龄相匹配的健康对照组33例,AD患者随机分为(1)dTMS组dTMS真刺激治疗;(2)药物组给予盐酸多奈哌齐5 mg/d治疗;(3)联合治疗组同时给予dTMS和盐

  16. Inductive reasoning in Alzheimer's disease. (United States)

    Smith, E E; Rhee, J; Dennis, K; Grossman, M


    We evaluated knowledge of basic level and superordinate semantic relations and the role of cognitive resources during inductive reasoning in probable Alzheimer's disease (AD). Nineteen mildly demented AD patients and 17 healthy control subjects judged the truthfulness of arguments with a premise and a conclusion that contain familiar concepts coupled with "blank" predicates, such as "Spiders contain phosphatidylcholine; therefore all insects contain phosphatidylcholine." Like healthy control subjects, AD patients were relatively insensitive to the typicality of the premise category when judging the strength of arguments with a conclusion containing a basic-level concept, but were relatively sensitive to typicality during judgments of arguments containing a superordinate in the conclusion. Moreover, AD patients resembled control subjects in judging arguments with an immediate superordinate in the conclusion compared to arguments with a distant superordinate. AD patients differed from control subjects because they could not take advantage of two premises in an argument containing basic-level concepts. We conclude that semantic knowledge is sufficiently preserved in AD to support inductive reasoning, but that limited cognitive resources may interfere with AD patients' ability to consider the entire spectrum of information available during semantic challenges.

  17. [Western diet and Alzheimer's disease]. (United States)

    Berrino, Franco


    Alzheimer Disease, characterised by a global impairment of cognitive functions, is more and more common in Western societies, both because of longer life expectancy and, probably, because of increasing incidence. Several hints suggest that this degenerative disease is linked to western diet, characterised by excessive dietary intake of sugar, refined carbohydrates (with high glycaemic index), and animal product (with high content of saturated fats), and decreased intake of unrefined seeds--cereals, legumes, and oleaginous seeds--and other vegetables (with high content of fibres, vitamins, polyphenols and other antioxidant substances, phytoestrogens) and, in several populations, of sea food (rich in n-3 fatty acids). It has been hypothesised, in fact, that AD, may be promoted by insulin resistance, decreased endothelial production of nitric oxide, free radical excess, inflammatory metabolites, homocysteine, and oestrogen deficiency. AD, therefore, could theoretically be prevented (or delayed) by relatively simple dietary measures aimed at increasing insulin sensitivity (trough reduction of refined sugars and saturated fats from meat and dairy products), the ratio between n-3 and n-6 fatty acids (e.g. from fish and respectively seed oils), antioxidant vitamins, folic acid, vitamin B6, phytoestrogens (vegetables, whole cereals, and legumes, including soy products), vitamin B12 (bivalve molluscs, liver), and Cr, K, Mg, and Si salts. This comprehensive improvement of diet would fit with all the mechanistic hypotheses cited above. Several studies, on the contrary, are presently exploring monofactorial preventive strategies with specific vitamin supplementation or hormonal drugs, without, however, appreciable results.

  18. Geriatric Dentistry and the Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Marcelo Coelho GOIATO


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

  19. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease (United States)


    ... 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...

  20. 75 FR 67899 - National Alzheimer's Disease Awareness Month, 2010 (United States)


    ... 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,...

  1. 77 FR 66519 - National Alzheimer's Disease Awareness Month, 2012 (United States)


    ... 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...

  2. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011 (United States)


    ... 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...

  3. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013 (United States)


    ... 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...

  4. 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

  5. Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET. (United States)

    Okamura, Nobuyuki; Furumoto, Shozo; Fodero-Tavoletti, Michelle T; Mulligan, Rachel S; Harada, Ryuichi; Yates, Paul; Pejoska, Svetlana; Kudo, Yukitsuka; Masters, Colin L; Yanai, Kazuhiko; Rowe, Christopher C; Villemagne, Victor L


    Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating the treatment efficacy of disease-specific therapeutics. In this study, we evaluated the clinical usefulness of a novel tau-imaging positron emission tomography tracer 18F-THK5105 in 16 human subjects including eight patients with Alzheimer's disease (three male and five females, 66-82 years) and eight healthy elderly controls (three male and five females, 63-76 years). All participants underwent neuropsychological examination and 3D magnetic resonance imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron emission tomography scans. Standard uptake value ratios at 90-100 min and 40-70 min post-injection were calculated for 18F-THK5105 and 11C-Pittsburgh compound B, respectively, using the cerebellar cortex as the reference region. As a result, significantly higher 18F-THK5105 retention was observed in the temporal, parietal, posterior cingulate, frontal and mesial temporal cortices of patients with Alzheimer's disease compared with healthy control subjects. In patients with Alzheimer's disease, the inferior temporal cortex, which is an area known to contain high densities of neurofibrillary tangles in the Alzheimer's disease brain, showed prominent 18F-THK5105 retention. Compared with high frequency (100%) of 18F-THK5105 retention in the temporal cortex of patients with Alzheimer's disease, frontal 18F-THK5105 retention was less frequent (37.5%) and was only observed in cases with moderate-to-severe Alzheimer's disease. In contrast, 11C-Pittsburgh compound B retention was highest in the posterior cingulate cortex, followed by the ventrolateral prefrontal, anterior cingulate, and superior temporal cortices, and did not correlate with 18F-THK5105 retention in the neocortex. In healthy control subjects, 18F-THK5105 retention was ∼10% higher in the mesial temporal cortex than in the

  6. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. (United States)

    Scheltens, P; Leys, D; Barkhof, F; Huglo, D; Weinstein, H C; Vermersch, P; Kuiper, M; Steinling, M; Wolters, E C; Valk, J


    Magnetic resonance imaging (MRI) has shown a great reduction in medial temporal lobe and hippocampal volume of patients with Alzheimer's disease as compared to controls. Quantitative volumetric measurements are not yet available for routine clinical use. We investigated whether visual assessment of medial temporal lobe atrophy (MTA) on plain MRI films could distinguish patients with Alzheimer's disease (n = 21) from age matched controls (n = 21). The degree of MTA was ascertained with a ranking procedure and validated by linear measurements of the medial temporal lobe including the hippocampal formation and surrounding spaces occupied by cerebrospinal fluid. Patients with Alzheimer's disease showed a significantly higher degree of subjectively assessed MTA than controls (p = 0.0005). Linear measurements correlated highly with subjective assessment of MTA and also showed significant differences between groups. Ventricular indices did not differ significantly between groups. In Alzheimer's disease patients the degree of MTA correlated significantly with scores on the mini-mental state examination and memory tests, but poorly with mental speed tests. This study shows that MTA may be assessed quickly and easily with plain MRI films. MTA shown on MRI strongly supports the clinical diagnosis of Alzheimer's disease, is related to memory function, and seems to occur earlier in the disease process than does generalised brain atrophy.

  7. 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)


    The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

  8. Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian network. (United States)

    Jin, Yan; Su, Yi; Zhou, Xiao-Hua; Huang, Shuai


    By 2050, it is estimated that the number of worldwide Alzheimer's disease (AD) patients will quadruple from the current number of 36 million, while no proven disease-modifying treatments are available. At present, the underlying disease mechanisms remain under investigation, and recent studies suggest that the disease involves multiple etiological pathways. To better understand the disease and develop treatment strategies, a number of ongoing studies including the Alzheimer's Disease Neuroimaging Initiative (ADNI) enroll many study participants and acquire a large number of biomarkers from various modalities including demographic, genotyping, fluid biomarkers, neuroimaging, neuropsychometric test, and clinical assessments. However, a systematic approach that can integrate all the collected data is lacking. The overarching goal of our study is to use machine learning techniques to understand the relationships among different biomarkers and to establish a system-level model that can better describe the interactions among biomarkers and provide superior diagnostic and prognostic information. In this pilot study, we use Bayesian network (BN) to analyze multimodal data from ADNI, including demographics, volumetric MRI, PET, genotypes, and neuropsychometric measurements and demonstrate our approach to have superior prediction accuracy.

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

    Directory of Open Access Journals (Sweden)

    Catricala Silvia


    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.

  10. La alimentación del enfermo de Alzheimer en el ámbito familiar Alzheimer`s disease patients nutrition in the domestic environment

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    J. J. Botella Trelis


    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

  11. Early Detection of Alzheimer's - A Crucial Requirement

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    Bukhari, Ijaz


    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.

  12. Current treatments for patients with Alzheimer disease. (United States)

    Osborn, Gerald G; Saunders, Amanda Vaughn


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

  13. Glycation in Parkinson's disease and Alzheimer's disease. (United States)

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


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

  14. 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


    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.

  15. Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

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    Fellmann Jere


    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.

  16. Stem cell treatment for Alzheimer's disease. (United States)

    Li, Ming; Guo, Kequan; Ikehara, Susumu


    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.

  17. Oxidative stress and Alzheimer disease. (United States)

    Christen, Y


    Research in the field of molecular biology has helped to provide a better understanding of both the cascade of biochemical events that occurs with Alzheimer disease (AD) and the heterogeneous nature of the disease. One hypothesis that accounts for both the heterogeneous nature of AD and the fact that aging is the most obvious risk factor is that free radicals are involved. The probability of this involvement is supported by the fact that neurons are extremely sensitive to attacks by destructive free radicals. Furthermore, lesions are present in the brains of AD patients that are typically associated with attacks by free radicals (eg, damage to DNA, protein oxidation, lipid peroxidation, and advanced glycosylation end products), and metals (eg, iron, copper, zinc, and aluminum) are present that have catalytic activity that produce free radicals. beta-Amyloid is aggregated and produces more free radicals in the presence of free radicals; beta-amyloid toxicity is eliminated by free radical scavengers. Apolipoprotein E is subject to attacks by free radicals, and apolipoprotein E peroxidation has been correlated with AD. In contrast, apolipoprotein E can act as a free radical scavenger and this behavior is isoform dependent. AD has been linked to mitochondrial anomalies affecting cytochrome-c oxidase, and these anomalies may contribute to the abnormal production of free radicals. Finally, many free radical scavengers (eg, vitamin E, selegeline, and Ginkgo biloba extract EGb 761) have produced promising results in relation to AD, as has desferrioxamine-an iron-chelating agent-and antiinflammatory drugs and estrogens, which also have an antioxidant effect.

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

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    G. Macchi


    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.

  19. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease. (United States)

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I


    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); PHypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; Phypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production.

  20. Diagnosis of Alzheimer's disease with [18F]PET in mild and asymptomatic stages. (United States)

    Drzezga, Alexander


    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.

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

  2. 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;


    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...... importance in the clinical decision making. We propose a method for computing automatically the volume of hippocampus using a modified multi-atlas segmentation framework, including an improved initialization of the framework and the correction of partial volume effect. The method produced a high similarity...... 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...

  3. The Use of Auditory Event-Related Potentials in Alzheimer's Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    Fabrizio Vecchio


    Full Text Available Event-related potentials (ERPs are important clinical and research instruments in neuropsychiatry, particularly due to their strategic role for the investigation of brain function. These techniques are often underutilized in the evaluation of neurological and psychiatric disorders, but ERPs are noninvasive instruments that directly reflect cortical neuronal activity. Previous studies using the P300, P3a, and MMN components of the ERP to study dementing illness are reviewed. The results suggest that particularly the P300 brain potential is sensitive to Alzheimer's disease processes during its early stages, and that easily performed stimulus discrimination tasks are the clinically most useful. Finally, these data suggest that the P300 ERP can aid in the diagnosis of dementia and may help in the assessment of early Alzheimer's disease.

  4. Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study

    NARCIS (Netherlands)

    Damian, M.; Hausner, L.; Jekel, K.; Richter, M.; Froelich, L.; Almkvist, O.; Boada, M.; Bullock, R.; Deyn, P.P. de; Frisoni, G.B.; Hampel, H.; Jones, R.W.; Kehoe, P.; Lenoir, H.; Minthon, L.; Olde Rikkert, M.G.M.; Rodriguez, G.; Scheltens, P.; Soininen, H.; Spiru, L.; Touchon, J.; Tsolaki, M.; Vellas, B.; Verhey, F.R.J.; Winblad, B.; Wahlund, L.O.; Wilcock, G.; Visser, P.J.


    Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures includ

  5. 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


    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

  6. 阿尔茨海默病新诊断标准的临床研究价值%Clinical and research value of the new diagnositc criteria for Alzheimer ’s disease

    Institute of Scientific and Technical Information of China (English)



    概述:在阿尔茨海默氏病(Alzheimer’s disease, AD)的诊断中采用生物标志物已日益得到重视,但在临床实践中使用生物标志物的可行性和价值仍然是有限的。然而,AD临床和制药研究中生物标志物的使用也许可以证明对明确AD的病理基础是非常有用的,并有助于提高在有效预防和治疗措施下的早期识别。此外,新诊断标准的广泛采用将提高不同研究结果之间的可比性,并为使用meta 分析方法合并和比较不同研究的结果创造了可能性—— 这种分析能够明确回答关于 AD 的病因、病程、预防和治疗等基本问题。%Summary:The use of biomarkers in the diagnosis of Alzheimer’s disease (AD) has been increasingly emphasized, but the feasibility and value of using biomarkers in clinical pracitce remain limited. However, the use of biomarkers in clinical and pharmaceutical research about AD may prove quite useful in clarifying the pathology underlying AD and, thus, help in the early identification of effective preventive and therapeutic interventions. Moreover, wide adoption of the new diagnostic criteria will improve comparability of research results across studies, and, thus, allow for the combination and comparison of study results using meta-analytic techniques–the types of analyses needed to definitively answer fundamental quesitons about the eitology, course, preveniton, and treatment of AD.

  7. Synchrotron FTIR microspectroscopy of Alzheimer's diseased brain tissue at the SRC beamline (United States)

    Bromberg, Pam S.; Gough, Kathleen M.; Ogg, Mandy; Del Bigio, M. R.; Julian, Robert


    Alzheimer's Disease is a neurodegenerative disorder marked by progressive cognitive decline. AD presents with many of the same clinical symptoms as senile dementia, but the diagnosis of AD must be confirmed by post-mortem examination of the morphological and histopathological features of the brain. The two classical lesions found in the cortical and hippocampal regions of the brain are the (beta) -amyloid- bearing neuritic plaques and the intraneuronal neurofibrillary tangles.

  8. 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


    We explored diffraction enhanced imaging (DEI) in both planar and computed tomography (CT) modes for early detection of beta amyloid deposition, a hallmark feature in Alzheimer's disease (AD). Since amyloid plaques precede clinical symptoms by years, their early detection is of great interest. These findings were correlated with results from synchrotron infrared microspectroscopic imaging and X-ray fluorescence microscopy, to determine the secondary structure of the amyloid beta protein and metal concentration in the amyloid plaques, respectively.

  9. Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease. (United States)

    Gao, Jie; Adam, Bao-Ling; Terry, Alvin V


    The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies.

  10. Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.


    McShane, R.; Gedling, K; Reading, M.; McDonald, B.; Esiri, M M; Hope, T


    The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Po...

  11. Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease. (United States)

    McShane, R; Gedling, K; Reading, M; McDonald, B; Esiri, M M; Hope, T


    The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

  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


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

    Sun, Fei; Hodge, David R


    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.

  14. Early diagnosis of Alzheimer's via PET probe

    Institute of Scientific and Technical Information of China (English)


    @@ 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.

  15. Structural Neuroimaging in Aging and Alzheimer's Disease

    NARCIS (Netherlands)

    Vernooij, Meike W.; Smits, Marion


    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

  16. Therapeutic potential of resveratrol in Alzheimer's disease


    Vingtdeux, Valérie; Dreses-Werringloer, Ute; Zhao, Haitian; Davies, Peter; Marambaud, Philippe


    Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent...

  17. Verbal Repetitions and Echolalia in Alzheimer's Discourse (United States)

    Da Cruz, Fernanda Miranda


    This article reports on an investigation of echolalic repetition in Alzheimer's disease (AD). A qualitative analysis of data from spontaneous conversations with MHI, a woman with AD, is presented. The data come from the DALI Corpus, a corpus of spontaneous conversations involving subjects with AD. This study argues that echolalic effects can be…

  18. 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


    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.

  19. Looking for Signs of Alzheimer's Disease (United States)

    Hodgson, Lynne Gershenson; Cutler, Stephen J.


    This study examined the correlates of symptom-seeking behavior for Alzheimer's disease (AD) among middle-aged persons. Symptom seeking, the tendency to search for signs of disease, is one manifestation of an individual's concern about developing AD. The data were obtained from a survey of two subsamples of 40-60 year old adults: 1) 108 adult…

  20. Alzheimer's disease: analyzing the missing heritability.

    Directory of Open Access Journals (Sweden)

    Perry G Ridge

    Full Text Available Alzheimer's disease (AD is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

  1. Aripiprazole in the treatment of Alzheimer's disease

    NARCIS (Netherlands)

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


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

  2. 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


    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

  3. Alzheimer disease : presenilin springs a leak

    NARCIS (Netherlands)

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


    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. 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.


    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

  5. Atorvastatin attenuates oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Cai Zhiyou; Yan Yong; Wang Yonglong


    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.

  6. Llama VHH as immunotherapeutics in Alzheimer's disease

    NARCIS (Netherlands)

    Dorresteijn, B.


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

  7. S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration. (United States)

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


    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.

  8. 78 FR 46590 - Office of the Assistant Secretary for Planning and Evaluation; Advisory Council on Alzheimer's... (United States)


    ... 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...

  9. Alzheimer and vascular brain diseases: Focal and diffuse subforms

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Alois Alzheimer is best known for his description of the pre-senile neurodegenerative disease named after him. However, his previous interest in vascular brain diseases, underlying cognitive and behavioral changes, was very strong. Besides describing the Arteriosclerotic atrophy of the brain and the arteriosclerotic subtype of Senile dementia which he viewed as main forms of vascular brain diseases, he also identified and described a series of conditions he considered subforms. These may be divided, as suggested by the authors of the present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and apoplectic. The subforms of the three groups present characteristic neuropathological features and clinical, cognitive and behavioral manifestations. These provide the basis, together with part of the main forms, for the contemporary condition known as Vascular Cognitive Impairment.

  10. Semantic memory impairment in the earliest phases of Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Gade, Anders; Stokholm, Jette


    The presence and the nature of semantic memory dysfunction in Alzheimer's disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD....... Five short neuropsychological tests sensitive to semantic memory and easily applicable in routine practice were administered to 102 patients with mild AD (Mini-Mental State Examination score above 19), 22 predementia AD patients and 58 healthy subjects. 'Category fluency' and 'naming of famous faces......' were the most frequently impaired tests in both patient groups. The study demonstrated that impairments on semantically related tests are common in mild AD and may exist prior to the clinical diagnosis. The results imply that assessment of semantic memory is relevant in the evaluation of patients...

  11. Art therapy for Alzheimer's disease and other dementias. (United States)

    Chancellor, Bree; Duncan, Angel; Chatterjee, Anjan


    Patients with dementias commonly experience neuropsychiatric symptoms that diminish their quality of life. Pharmacologic treatments for these symptoms are limited in their efficacy. In the absence of near-future prospects for a cure for degenerative dementias, treatments that improve neuropsychiatric symptoms and quality of life are needed. We explore the hypothesis that art therapy is useful in dementia by reviewing the extant literature. With appropriate structure, patients with dementia can produce and appreciate visual art. Case studies and several small trials suggest that art therapy engages attention, provides pleasure, and improves neuropsychiatric symptoms, social behavior, and self-esteem. Whether these benefits generalize beyond the studio remains unknown. We offer a theoretical framework that motivates the use of art therapy and propose that clinical enquiry to establish methods, assess efficacy, and define optimal conditions for the use of art therapy in Alzheimer's and other dementing disorders is timely.

  12. Insulin resistance: an emerging link in Alzheimer's disease. (United States)

    Medhi, Bikash; Chakrabarty, Mrinmoy


    Relentless progression of Alzheimer's disease (AD) poses a grave situation for the biomedical community to tackle. Agents starting as hot favorites in clinical trials have failed in later stages and it is time we reconsidered our approaches to intervene the disease. Quite some interesting work in the last decade has introduced a new school of thought which factors in neuronal glycemic imbalance as a major component for the development of AD. Insulin resistance in the brain has brought forward subsequent sequelae which might work towards amyloid accretion and/or tau hyperphosphorylation. It is also pointed out that insulin works by distributing iron to neuronal tissue and an insulin resistant state throws it off gear leading to iron overloading of neurons which is ultimately detrimental. A relatively recent investigation finds the role of c-Jun-N-terminal kinase (JNK3) in AD which also seems to bear a link with insulin resistance.

  13. Dependence as a unifying construct in defining Alzheimer's disease severity. (United States)

    McLaughlin, Trent; Feldman, Howard; Fillit, Howard; Sano, Mary; Schmitt, Frederick; Aisen, Paul; Leibman, Christopher; Mucha, Lisa; Ryan, J Michael; Sullivan, Sean D; Spackman, D Eldon; Neumann, Peter J; Cohen, Joshua; Stern, Yaakov


    This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.

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

    CERN Document Server

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


    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. Using biomarkers to improve detection of Alzheimer's disease. (United States)

    Biagioni, Milton C; Galvin, James E


    Disease-modifying approaches for Alzheimer's disease (AD) might be most effective when initiated very early in the course, before the pathologic burden and neuronal and synaptic degeneration make it unlikely that halting disease progression would have a significant impact on patient outcomes. Biomarkers of disease may provide important avenues of research to enhance the diagnosis of individuals with early AD and could assist in the identification of those individuals at risk for developing AD. However, for such biomarkers to become clinically useful, long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes to the longitudinal course of the disease. The objective of this article is to review recent progress in AD biomarkers for the early diagnosis, classification, progression and prediction of AD and their usefulness in new treatment trials.

  16. Diagnostic Tests for Alzheimer's Disease: Rationale, Methodology, and Challenges

    Directory of Open Access Journals (Sweden)

    S. E. Mason


    Full Text Available There has been a large increase in the amount of research seeking to define or diagnose Alzheimer's disease before patients develop dementia. If successful, this would principally have clinical benefits both in terms of treatment as well as risk modification. Moreover, a better method for diagnosing predementia disease would assist research which seeks to develop such treatments and risk modification strategies. The evidence-based definition of a diagnostic test's accuracy is fundamental to achieve the above goals and to address this, the Cochrane Collaboration has established a Diagnostic Test Accuracy group dedicated to examining the utility and accuracy of proposed tests in dementia and cognitive impairment. We present here the assumptions and observations underpinning the chosen methodology as well as the initial methodological approach decided upon.

  17. Neuropeptides in Alzheimer's disease: from pathophysiological mechanisms to therapeutic opportunities. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Pasquale Scarnera


    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.

  19. Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer's disease. (United States)

    Yan, Riqiang; Fan, Qingyuan; Zhou, John; Vassar, Robert


    Over the past two decades, many studies have identified significant contributions of toxic β-amyloid peptides (Aβ) to the etiology of Alzheimer's disease (AD), which is the most common age-dependent neurodegenerative disease. AD is also recognized as a disease of synaptic failure. Aβ, generated by sequential proteolytic cleavages of amyloid precursor protein (APP) by BACE1 and γ-secretase, is one of major culprits that cause this failure. In this review, we summarize current findings on how BACE1-cleaved APP products impact learning and memory through proteins localized on glutamatergic, GABAergic, and dopaminergic synapses. Considering the broad effects of Aβ on all three types of synapses, BACE1 inhibition emerges as a practical approach for ameliorating Aβ-mediated synaptic dysfunctions. Since BACE1 inhibitory drugs are currently in clinical trials, this review also discusses potential complications arising from BACE1 inhibition. We emphasize that the benefits of BACE1 inhibitory drugs will outweigh the concerns.

  20. 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.