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Sample records for alzheimer disease-like clinical

  1. Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

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    Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

    2011-01-01

    Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiaochuan Wang

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

  4. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

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    Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

    2011-08-01

    Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline.

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    Vom Berg, Johannes; Prokop, Stefan; Miller, Kelly R; Obst, Juliane; Kälin, Roland E; Lopategui-Cabezas, Ileana; Wegner, Anja; Mair, Florian; Schipke, Carola G; Peters, Oliver; Winter, York; Becher, Burkhard; Heppner, Frank L

    2012-12-01

    The pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-β (Aβ). Using the APPPS1 Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in APPPS1 mice. Furthermore, intracerebroventricular delivery of antibodies to p40 significantly reduced the concentration of soluble Aβ species and reversed cognitive deficits in aged APPPS1 mice. The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits.

  6. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

    DEFF Research Database (Denmark)

    Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

    2017-01-01

    , but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild....... In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APPSWE/PS1δE9 genotype.......Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD...

  7. Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice.

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    Prokop, Stefan; Miller, Kelly R; Drost, Natalia; Handrick, Susann; Mathur, Vidhu; Luo, Jian; Wegner, Anja; Wyss-Coray, Tony; Heppner, Frank L

    2015-10-19

    Although central nervous system-resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer's disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell-based therapies for AD. © 2015 Prokop et al.

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

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

    2014-08-18

    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. Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.

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    Savas, Jeffrey N; Wang, Yi-Zhi; DeNardo, Laura A; Martinez-Bartolome, Salvador; McClatchy, Daniel B; Hark, Timothy J; Shanks, Natalie F; Cozzolino, Kira A; Lavallée-Adam, Mathieu; Smukowski, Samuel N; Park, Sung Kyu; Kelly, Jeffery W; Koo, Edward H; Nakagawa, Terunaga; Masliah, Eliezer; Ghosh, Anirvan; Yates, John R

    2017-11-28

    Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARPγ-2, a key AMPAR-trafficking protein. Expression of TARPγ-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Protective effects of different exercise modalities in an Alzheimer's disease-like model.

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    Özbeyli, Dilek; Sarı, Gülce; Özkan, Naziye; Karademir, Betül; Yüksel, Meral; Çilingir Kaya, Özlem Tuğçe; Kasımay Çakır, Özgür

    2017-06-15

    Our aim was to investigate the probable protective effects of aerobic, resistance and combined exercise methods on ovariectomy and d-galactose induced Alzheimer's Disease (AD)-like model. d-galactose (100mg/kg) or saline were administered intraperitoneally for 6 weeks to ovariectomized or sham-operated rats (n=8/group). Aerobic (AE), resistance (RE) and combined exercises (CE) (aerobic+resistance) were performed for 3 times a week for 6 weeks. Anxiety level and cognitive functions were evaluated via hole-board and object recognition tests. Brain myeloperoxidase, malondialdehyde, nitric oxide activity, lucigenin-enhanced chemiluminescence, glutathione and serum insulin like growth factor-I (IGF-I) assays were done. Hippocampal mRNA levels of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and amyloid precursor protein 695 (APP695) were measured. Amyloid Beta (Aβ), NGF, BDNF, IGF-I immunoreactive neurons were evaluated. Freezing time were increased in AD-like model and decreased back with AE (pexercise types (pexercises (pexercise types in cortex (pexercise models may have protective effects in development stage of AD via reducing oxidative stress and Aβ scores, and by improving antioxidant system and brain plasticity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Dani M Long

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

  13. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice.

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    Von Linstow, C U; Severino, M; Metaxas, A; Waider, J; Babcock, A A; Lesch, K P; Gramsbergen, J B; Finsen, B

    2017-09-01

    Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP SWE /PS1 ΔE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APP SWE /PS1 ΔE9 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Association of cerebrovascular dysfunction with the development of Alzheimer's disease-like pathology in OXYS rats.

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    Stefanova, Natalia A; Maksimova, Kseniya Yi; Rudnitskaya, Ekaterina A; Muraleva, Natalia A; Kolosova, Nataliya G

    2018-02-09

    Cerebrovascular dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD): the most common cause of dementia in the elderly. The involvement of neurovasculature disorders in the progression of AD is now increasingly appreciated, but whether they represent initial factors or late-stage pathological changes during the disease is unclear. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, we evaluated contributions of cerebrovascular alterations to the disease development. At preclinical, early, and advanced stages of AD-like pathology, in the hippocampus of OXYS and Wistar (control) rats, we evaluated (i) the blood vessel state by histological and electron-microscopic analyses; (ii) differences in gene expression according to RNA sequencing (RNA-Seq) to identify the metabolic processes and pathways associated with blood vessel function; (iii) the amount of vascular endothelial growth factor (VEGF) by western blot and immunohistochemical analysis. We observed a loss of hippocampal blood vessel density and ultrastructural changes of those blood vessels in OXYS rats at the early stage of AD-like pathology. There were significant alterations in the vessels and downregulation of VEGF with an increased amount of amyloid β 1-42 there at the advanced stage of the disease. According to RNA-Seq data analysis, major alterations in cerebrovascular processes of OXYS rats were associated with blood vessel development, circulatory system processes, the VEGF signaling pathway, and vascular smooth muscle contraction. At preclinical and early stages of the AD-like pathology, these processes were upregulated and then downregulated with age. At the advanced stage in OXYS rats, differentially expressed genes (DEGs) were associated with downregulation of cerebrovascular function as compared to Wistar rats. Among the 46 DEGs at the preclinical stage of the disease, 28 DEGs at the early stage, and among 85 DEGs at the advanced

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

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

    2016-05-01

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

  16. 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

    2010-01-01

    Full Text Available Down's syndrome (DS, trisomy 21 represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD. We compared two cases of DS with APOE 3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (A42 burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of A42 could relate to the cases' similar life-time accumulation of A due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP. The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of A42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary. Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis.

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

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    Guilherme Riccioppo Rodrigues

    2011-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Liana Lisboa Fernandez

    2005-03-01

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

  19. Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

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    Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

    2016-06-01

    Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

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

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

    2016-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice.

    Science.gov (United States)

    Liu, Hui-li; Zhao, Gang; Zhang, He; Shi, Li-de

    2013-11-01

    Previously our study has demonstrated that long-term treadmill exercise improved cognitive deficit in APP/PS1 transgenic mice of Alzheimer's disease (AD) paralleled by enhanced long-term potentiation (LTP). The present study was undertaken to further investigate whether the treadmill running could inhibit the progression of Alzheimer's disease (AD)-like neuropathology in hippocampus of the APP/PS1 mouse models of AD, and to define a potential molecular mechanism underlying the exercise-induced reduction in AD-like neuropathology. Five months of treadmill exercise resulted in a robust reduction in β-amyloid (Aβ) deposition and tau phosphorylation in the hippocampus of APP/PS1 mice. This was accompanied by a significant decrease in APP phosphorylation and PS1 expression. We also observed GSK3, rather than CDK5, was inhibited by treadmill exercise. These results indicate that treadmill exercise is sufficient to inhibit the progression of AD-like neuropathology in the hippocampus of APP/PS1 transgenic mouse model, and may mediate APP processing in favor of reduced Aβ deposition. In addition, we demonstrate that treadmill exercise attenuates AD-like neuropathology in AD transgenic mice via a GSK3 dependent signaling pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Alzheimer's Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory 'Wounding' to Anti-inflammatory 'Healing'.

    Science.gov (United States)

    He, Jiang; Liao, Tao; Zhong, Guo-Xin; Zhang, Ji-Da; Chen, Yan-Ping; Wang, Qi; Zeng, Qing-Ping

    2017-01-01

    The etiological initiators of neuroinflammation remain inconclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In contrast, electroacupuncture (EA) elevates TNF-α/IL-8 and declines IL-10/TH at first, but declines TNF-α/IL-8 and elevates IL-10/TH later. Upon impact on mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates but secondly attenuates CC-triggered signaling cascades leading to oxidation, nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises neurodegeneration by decreasing amyloid- β peptide (Aβ) and phosphorylated tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting biosynthetic enzyme choline acetyltransferase (ChAT). Conclusively, EA initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase brain pathogenesis via conversion from pro-inflammatory microglia to anti-inflammatory microglia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling.

    Science.gov (United States)

    Kang, Somang; Kim, Chul-Hoon; Jung, Hosung; Kim, Eosu; Song, Ho-Taek; Lee, Jong Eun

    2017-02-01

    The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

    Science.gov (United States)

    Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

    2014-08-01

    Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Wang, Bing; Tanaka, Kaoru; Ji, Bin

    2014-01-01

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

  7. Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis.

    Science.gov (United States)

    Briggs, Denise Isabelle; Defensor, Erwin; Memar Ardestani, Pooneh; Yi, Bitna; Halpain, Michelle; Seabrook, Guy; Shamloo, Mehrdad

    2017-01-01

    Emerging evidence suggests that endoplasmic reticulum (ER) stress may be involved in the pathogenesis of Alzheimer's disease (AD). Recently, pharmacological modulation of the eukaryotic translation initiation factor-2 (eIF2α) pathway was achieved using an integrated stress response inhibitor (ISRIB). While members of this signaling cascade have been suggested as potential therapeutic targets for neurodegeneration, the biological significance of this pathway has not been comprehensively assessed in animal models of AD. The present study investigated the ER stress pathway and its long-term modulation utilizing in vitro and in vivo experimental models of tauopathy (MAPT P301S)PS19 and amyloidosis (APP Swe ). We report that thapsigargin induces activating transcription factor-4 (ATF4) in primary cortical neurons (PCNs) derived from rat and APP Swe nontransgenic (nTg) and transgenic (Tg) mice. ISRIB mitigated the induction of ATF4 in PCNs generated from wild-type (WT) but not APP Swe mice despite partially restoring thapsigargin-induced translational repression in nTg PCNs. In vivo , C57BL/6J and PS19 mice received prolonged, once-daily administration of ISRIB. While the compound was well tolerated by PS19 and C57BL/6J mice, APP Swe mice treated per this schedule displayed significant mortality. Thus, the dose was reduced and administered only on behavioral test days. ISRIB did not improve learning and memory function in APP Swe Tg mice. While ISRIB did not reduce tau-related neuropathology in PS19 Tg mice, no evidence of ER stress-related dysfunction was observed in either of these Tg models. Taken together, the significance of ER stress and the relevance of these models to the etiology of AD require further investigation.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

    Knebl, Janice A; Patki, Deepti

    2010-09-01

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

  10. Globalization of Alzheimer's disease clinical trials

    Science.gov (United States)

    2011-01-01

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

  11. Globalization of Alzheimer's disease clinical trials.

    Science.gov (United States)

    Cummings, Jeffrey; Reynders, Robert; Zhong, Kate

    2011-08-17

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

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

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  13. Semantic Memory in the Clinical Progression of Alzheimer Disease.

    Science.gov (United States)

    Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

    2017-09-01

    Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

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

    Directory of Open Access Journals (Sweden)

    Meng-qiu LI

    2014-03-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  16. The clinical use of structural MRI in Alzheimer disease

    Science.gov (United States)

    Frisoni, Giovanni B.; Fox, Nick C.; Jack, Clifford R.; Scheltens, Philip; Thompson, Paul M.

    2010-01-01

    Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment. PMID:20139996

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

    Directory of Open Access Journals (Sweden)

    Martin R. Farlow

    2013-09-01

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

  18. Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

    Directory of Open Access Journals (Sweden)

    Adalberto Studart Neto

    Full Text Available ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD, when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

  19. Nutritional interventions for Alzheimer's prevention: a clinical precision medicine approach.

    Science.gov (United States)

    Schelke, Matthew W; Hackett, Katherine; Chen, Jaclyn L; Shih, Chiashin; Shum, Jessica; Montgomery, Mary E; Chiang, Gloria C; Berkowitz, Cara; Seifan, Alon; Krikorian, Robert; Isaacson, Richard Scott

    2016-03-01

    Alzheimer's disease (AD) is a major source of morbidity and mortality, with the disease burden expected to rise as the population ages. No disease-modifying agent is currently available, but recent research suggests that nutritional and lifestyle modifications can delay or prevent the onset of AD. However, preventive nutritional interventions are not universally applicable and depend on the clinical profile of the individual patient. This article reviews existing nutritional modalities for AD prevention that act through improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress, and discusses how they may be modified on the basis of individual biomarkers, genetics, and behavior. In addition, we report preliminary results of clinical application of these personalized interventions at the first AD prevention clinic in the United States. The use of these personalized interventions represents an important application of precision medicine techniques for the prevention of AD that can be adopted by clinicians across disciplines. © 2016 New York Academy of Sciences.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  2. Diagnosis of preclinical Alzheimer's disease in a clinical setting.

    Science.gov (United States)

    Visser, P J; Verhey, F R; Ponds, R W; Jolles, J

    2001-12-01

    The aim of the study was to investigate whether the preclinical stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this end we investigated whether subjects with preclinical AD could be differentiated from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. Twenty-three subjects with preclinical AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects with very mild AD-type dementia were selected from a memory clinic population. Variables that were used to differentiate the groups were demographic variables, the Mini-Mental State Examination score, performance on cognitive tests, measures of functional impairment, and measures of noncognitive symptomatology. Age and the scores for the delayed recall task could best discriminate between subjects with preclinical AD and subjects with nonprogressive mild cognitive impairment. The overall accuracy was 87%. The score on the Global Deterioration Scale and a measure of intelligence could best discriminate between subjects with preclinical AD and subjects with very mild AD-type dementia. The overall accuracy was 85%. Subjects with preclinical AD can be distinguished from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. This means that preclinical AD is a diagnostic entity for which clinical criteria should be developed.

  3. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

    Science.gov (United States)

    Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos

    2017-11-01

    Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

  4. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

    Directory of Open Access Journals (Sweden)

    Maria Victoria Fernández

    2017-11-01

    Full Text Available Alzheimer disease (AD, Frontotemporal lobar degeneration (FTD, Amyotrophic lateral sclerosis (ALS and Parkinson disease (PD have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

  5. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010.

    Science.gov (United States)

    Beach, Thomas G; Monsell, Sarah E; Phillips, Leslie E; Kukull, Walter

    2012-04-01

    The neuropathologic examination is considered to provide the gold standard for Alzheimer disease (AD). To determine the accuracy of currently used clinical diagnostic methods, clinical and neuropathologic data from the National Alzheimer's Coordinating Center, which gathers information from the network of National Institute on Aging (NIA)-sponsored Alzheimer Disease Centers (ADCs), were collected as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) between 2005 and 2010. A database search initially included all 1198 subjects with at least one UDS clinical assessment and who had died and been autopsied; 279 were excluded as being not demented or because critical data fields were missing. The final subject number was 919. Sensitivity and specificity were determined based on "probable" and "possible" AD levels of clinical confidence and 4 levels of neuropathologic confidence based on varying neuritic plaque densities and Braak neurofibrillary stages. Sensitivity ranged from 70.9% to 87.3%; specificity ranged from 44.3% to 70.8%. Sensitivity was generally increased with more permissive clinical criteria and specificity was increased with more restrictive criteria, whereas the opposite was true for neuropathologic criteria. When a clinical diagnosis was not confirmed by minimum levels of AD histopathology, the most frequent primary neuropathologic diagnoses were tangle-only dementia or argyrophilic grain disease, frontotemporal lobar degeneration, cerebrovascular disease, Lewy body disease and hippocampal sclerosis. When dementia was not clinically diagnosed as AD, 39% of these cases met or exceeded minimum threshold levels of AD histopathology. Neurologists of the NIA-ADCs had higher predictive accuracy when they diagnosed AD in subjects with dementia than when they diagnosed dementing diseases other than AD. The misdiagnosis rate should be considered when estimating subject numbers for AD studies, including clinical trials and epidemiologic

  6. Neuroinflammation and Alzheimer disease: clinical and therapeutic implications

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-12-01

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

  9. TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia.

    Science.gov (United States)

    James, Bryan D; Wilson, Robert S; Boyle, Patricia A; Trojanowski, John Q; Bennett, David A; Schneider, Julie A

    2016-11-01

    Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP ) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n = 398) and without dementia ( n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer's disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Clinical diagnosis by computed tomography on Alzheimer type dementia

    International Nuclear Information System (INIS)

    Imai, Yukimichi

    1983-01-01

    The relationships of CT findings, intellectual impairment by psychological assessment and severity of dementia by clinical evaluation were studied on 109 patients with clinical diagnosis of Alzheimer type dementia (AD) and 43 controls. CT examinations were carried out on three tomographic sections, that is, a section through anterior and posterior horns of lateral ventricles, a section through cellae mediae of lateral ventricles and a section through cortex with intracranial space of 60-80 cm 2 . In the three tomographic sections, CSF space percent and half width full max (HWFM) in the histogram corresponding to brain tissue were employed as indexes of brain atrophy by CT. Psychological evaluation of dementia was made by using Hasegawa's dementia scale (HDS). The present study revealed the following findings. though CSF% in the sections through lateral ventricles significantly correlated with age, it was more significantly correlated with HDS and CDR(clinical dementia rating) scores, respectively. This finding seems to mean that the effect of dementia is so great as to override the effect of dementia. In the cortex slice, the correlations between CSF% and HDS and CDR scores were very low, though they were significant. HWFM in the same slice, showed the moderate and significant correlations with HDS and CDR scores, respectively, comparing with no relationship between HWFM and age. Concerning mean CSF% and HWFM of each group according to CDR staging, they increased with advancement of dementia. The significant differences between the groups by CDR, however, were not always obtained. According to CT indexes as independent variable, the normal subject were discriminated from the demented subjects in 82.6% of the total by discriminat analysis. (J.P.N.)

  12. Clinical evaluation of patients with moderate to severe Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Paulo Rogério Borges Rosmaninho Varandas

    Full Text Available Abstract Today, Alzheimer disease has become a serious risk to individual and public health, due to the significant incapacity it causes patients, its influence on family members and caregivers, along with the ensuing direct and indirect costs. Objectives: To build the profile of patients with moderate/severe AD, in the Geriatric Clinic Service of Cognitive Alterations of the Medical School at Universidade de São Paulo, by studying demential and comorbidity conditions and the degree of effectiveness of the therapies applied. Methods: 30 patients with moderate or severe AD were selected, (77.8±7.29 years. Age, sex, schooling, prevalent comorbidities/treatments and respective clinical-laboratorial effectiveness were analyzed. Instruments were applied to evaluate the cognitive and behavioral condition and dementia control therapies. Results: Most frequent comorbidities were arterial hypertension (80% and diabetes (43.3%. A maximum dose of rivastigmine was observed in 43% of the patients, where 76% experienced adverse effects. Severe patients presented more cases of uncontrolled comorbidities, such as hypertension (P<0.001, as well as more behavioral alterations (P<0.001 and functional loss (P=0.004. Patients with greater behavioral alterations proved to be more functionally dependent (P=0.002, having less comorbidity control (P=0.004. Conclusions: In this population, a high incidence of comorbidities, frequent behavioral alterations and difficulties in therapy management were noted due to the severity of the dementia condition. New therapies for more adequate control of severe dementia should be studied.

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

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

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

  14. Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

    OpenAIRE

    Forlenza,Orestes V.; Diniz,Breno S.; Talib,Leda L.; Radanovic,Marcia; Yassuda,Monica S.; Ojopi,Elida B.; Gattaz,Wagner F.

    2010-01-01

    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...

  15. Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer?s Disease: Determinants and Level of Change Observed

    OpenAIRE

    Lacey, Loretto; Bobula, Joel; Niecko, Timothy; Leibman, Christopher

    2016-01-01

    Introduction We evaluate the association between caregiver (informal) time/cost and illness severity from two recently completed clinical trials of an investigational drug for Alzheimer?s disease (AD). Methods Changes from baseline caregiver time were calculated and treatment effects analyzed using a restricted maximum likelihood-based mixed model for repeated measures. Four separate models were then estimated to examine the association between caregiver time costs and the clinical endpoints ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-12-15

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

  17. Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice

    DEFF Research Database (Denmark)

    Slats, Diane; Spies, Petra E; Sjögren, Magnus J C

    2010-01-01

    Analysis of the brain specific biomarkers amyloid beta(42) (Abeta(42)) and total tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and specificity of more than 85% for differentiating Alzheimer's Disease (AD) from non-demented controls. International guidelines are contradictory...

  18. Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

    Science.gov (United States)

    Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

    2017-09-01

    Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

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

    International Nuclear Information System (INIS)

    Golebiowski, M.; Barcikowska, M.; Pfeffer-Baczuk, A.; Luczywek, E.

    1994-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guoyan Yang

    Full Text Available 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.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: CRD42012003249.20 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.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 included trials.

  1. Determinants of global clinical change assessment in patients with early Alzheimer's disease

    NARCIS (Netherlands)

    Claus, J. J.; Teunisse, S.; Walstra, G. J.; van Gool, W. A.

    1998-01-01

    Global clinical impression (GCI) of change is assumed to integrate aspects of both cognitive and noncognitive functioning. We evaluated 140 consecutive patients with probable (n = 90) and possible (n = 50) early Alzheimer's disease at baseline and after 6 months with measurements of global cognitive

  2. Early-onset Alzheimer disease clinical variants: Multivariate analyses of cortical thickness

    NARCIS (Netherlands)

    Ridgway, G.R.; Lehmann, M.; Barnes, J.; Rohrer, J.D.; Warren, J.D.; Crutch, S.J.; Fox, N.C.

    2012-01-01

    Objective: To assess patterns of reduced cortical thickness in different clinically defined variants of early-onset Alzheimer disease (AD) and to explore the hypothesis that these variants span a phenotypic continuum rather than represent distinct subtypes. Methods: The case-control study included

  3. [Clinical stages of patients with Alzheimer disease treated in specialist clinics in Spain. The EACE study].

    Science.gov (United States)

    Alom Poveda, J; Baquero, M; González-Adalid Guerreiro, M

    2013-10-01

    The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSEde Neurología. Published by Elsevier Espana. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sei J Lee

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

  5. Alzheimer's Disease: Lessons Learned from Amyloidocentric Clinical Trials.

    Science.gov (United States)

    Soejitno, Andreas; Tjan, Anastasia; Purwata, Thomas Eko

    2015-06-01

    Alzheimer's disease (AD) is one of the most debilitating neurodegenerative diseases and is predicted to affect 1 in 85 people by 2050. Despite much effort to discover a therapeutic strategy to prevent progression or to cure AD, to date no effective disease-modifying agent is available that can prevent, halt, or reverse the cognitive and functional decline of patients with AD. Several underlying etiologies to this failure are proposed. First, accumulating evidence from past trials suggests a preventive as opposed to therapeutic paradigm, and the precise temporal and mechanistic relationship of β-amyloid (Aβ) and tau protein should be elucidated to confirm this hypothesis. Second, we are in urgent need of revised diagnostic criteria to support future trials. Third, various technical and methodological improvements are required, based on the lessons learned from previous failed trials.

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

    Science.gov (United States)

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

    2013-04-01

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

  7. The ADAS-cog and clinically meaningful change in the VISTA clinical trial of galantamine for Alzheimer's disease.

    Science.gov (United States)

    Rockwood, Kenneth; Fay, Sherri; Gorman, Mary

    2010-02-01

    A minimum 4-point change at 6 months on the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) is deemed clinically important, but this cut-point has been little studied in relation to clinical meaningfulness. In an investigator-initiated, clinical trial of galantamine, we investigated the extent to which a 4-point change classifies goal attainment by individual patients. Secondary analysis of the video imaging synthesis of treating Alzheimer's disease (VISTA) study: a 4-month, multi-centre, parallel-group, double-blind, placebo-controlled, trial of galantamine in 130 mild-moderate Alzheimer's disease patients (4-month open-label follow-up). ADAS-cog responses at 6 months were compared with outcomes on three clinical measures: clinician's interview based impression of change-plus caregiver input (CIBIC+), patient/carer-goal attainment scaling (PGAS) and clinician-GAS (CGAS). Thirty-seven of 99 patients improved by > or = 4 points on the ADAS-cog at 6 months, and 16/99 showed > or = 4-point worsening. ADAS-cog change scores correlated notionally to modestly with changes on the CGAS (r = -0.31), the PGAS (r = -0.29) and the CIBIC+ (r = 0.31). As a group, patients with ADAS-cog improvement were significantly more likely to improve on the clinical measures; those who worsened showed non-significant clinical decline. Individually, about half were misclassified in relation to each clinical measure; often when the ADAS-Cog detected 'no change', clinically meaningful effects could be detected. Even so, no ADAS-Cog cut-point optimally classified patients' clinical responses. A 4-point ADAS-cog change at 6 months is clinically meaningful for groups. Substantial individual misclassification between the ADAS-cog and clinical measures suggests no inherent meaning to a 4-point ADAS-cog change for a given patient.

  8. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

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

    Science.gov (United States)

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

    2015-01-01

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

  10. The contribution of single photon emission computed tomography in the clinical assessment of Alzheimer type dementia

    International Nuclear Information System (INIS)

    Boudousq, V.; Collombier, L.; Kotzki, P.O.

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-05

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

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

    International Nuclear Information System (INIS)

    Song Hua

    2009-01-01

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

  13. Clinical Trial of a Home Safety Toolkit for Alzheimer's Disease

    OpenAIRE

    Horvath, Kathy J.; Trudeau, Scott A.; Rudolph, James L.; Trudeau, Paulette A.; Duffy, Mary E.; Berlowitz, Dan

    2013-01-01

    This randomized clinical trial tested a new self-directed educational intervention to improve caregiver competence to create a safer home environment for persons with dementia living in the community. The sample included 108 patient/caregiver dyads: the intervention group (n = 60) received the Home Safety Toolkit (HST), including a new booklet based on health literacy principles, and sample safety items to enhance self-efficacy to make home safety modifications. The control group (n = 48) rec...

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

    Science.gov (United States)

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

    2017-05-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  16. Impact of cerebro-spinal fluid biomarkers of Alzheimer's disease in clinical practice: a multicentric study.

    Science.gov (United States)

    Mouton-Liger, François; Wallon, David; Troussière, Anne-Cécile; Yatimi, Rachida; Dumurgier, Julien; Magnin, Eloi; de la Sayette, Vincent; Duron, Emannuelle; Philippi, Nathalie; Beaufils, Emilie; Gabelle, Audrey; Croisile, Bernard; Robert, Philippe; Pasquier, Florence; Hannequin, Didier; Hugon, Jacques; Paquet, Claire

    2014-01-01

    CSF biomarkers of Alzheimer's disease are well validated in clinical research; however, their pragmatic utility in daily practice is still unappreciated. These biomarkers are used in routine practice according to Health Authority Recommendations. In 604 consecutive patients explored for cognitive disorders, questionnaires were prospectively proposed and filled. Before and after CSF biomarker results, clinicians provided a diagnosis and an estimate of their diagnostic confidence. Analysis has compared the frequency of diagnosis before and after CSF biomarker results using the net reclassification improvement (NRI) method. We have evaluated external validity comparing with data of French Bank National of AD (BNA). A total of 561 patients [Alzheimer's disease (AD), n = 253; non-AD, n = 308] were included (mean age, 68.6 years; women, 52 %). Clinically suspected diagnosis and CSF results were concordant in 65.2 % of cases. When clinical hypothesis and biological results were discordant, a reclassification occurred in favour of CSF biomarkers results in 76.9 %. The NRI was 39.5 %. In addition, the results show a statistically significant improvement in clinician confidence for their diagnosis. In comparison with BNA data, patients were younger and more frequently diagnosed with AD. Clinicians tend to heavily rely on the CSF AD biomarkers results and are more confident in their diagnoses using CSF AD biomarkers. Thus, these biomarkers appear as a key tool in clinical practice.

  17. Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

    Directory of Open Access Journals (Sweden)

    Matej Mihelčić

    Full Text Available Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD. We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A, which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01 were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP in the non-amyloidogenic pathway

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

  20. Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

    Science.gov (United States)

    Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

    2014-12-01

    To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Tacrine for Alzheimer's disease.

    Science.gov (United States)

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

    2000-01-01

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

  3. 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.

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

    Science.gov (United States)

    Auclair, Ursula; Epstein, Cynthia; Mittelman, Mary

    2009-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Pedro Andre Kowacs

    2013-07-01

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

  6. [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].

    Science.gov (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

    2017-04-01

    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. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials.

    Science.gov (United States)

    Grill, Joshua D; Raman, Rema; Ernstrom, Karin; Aisen, Paul; Dowsett, Sherie A; Chen, Yun-Fei; Liu-Seifert, Hong; Hake, Ann Marie; Miller, David S; Doody, Rachelle S; Henley, David B; Cummings, Jeffrey L

    2015-01-01

    Most Alzheimer's disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region. We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). We assigned 31 participating nations to 7 geographic regions: North America, South America/Mexico, Western Europe/Israel, Eastern Europe/Russia, Australia/South Africa, Asia, and Japan. North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ε4 carriers, and participants with spouse study partners, whereas Asia, Eastern Europe/Russia, and South America/Mexico had lower proportions for these variables. North America and South America/Mexico enrolled older subjects, whereas Asia and South America/Mexico enrolled less-educated participants than the remaining regions. Approved AD therapy use differed among regions (range: 73% to 92%) and was highest in North America, Western Europe/Israel, and Japan. Dual therapy was most frequent in North America (48%). On the MMSE, North America, Western Europe/Israel, Japan, and Australia/South Africa had higher (better) scores, and Asia, South America/Mexico, and Eastern Europe/Russia had lower scores. Eastern Europe/Russia had more impaired ADAS-cog11 scores than all other regions. Eastern Europe/Russia and South America/Mexico had more impaired scores for the ADCS-ADL and the CDR-SB. Mean scores for

  8. [Mindfulness-based stimulation in advanced Alzheimer's disease: A comparative, non-inferiority, clinical pilot study].

    Science.gov (United States)

    Quintana Hernández, Domingo Jesús; Miró Barrachina, María Teresa; Ibáñez Fernández, Ignacio; Santana del Pino, Angelo; Rojas Hernández, Jaime; Rodríguez García, Javier; Quintana Montesdeoca, María del Pino

    2015-01-01

    A longitudinal study was conducted in order to analyze the feasibility, safety, and effects of the practice of mindfulness, relaxation and cognitive stimulation on the evolution of Alzheimer's disease, with the aim of testing the equivalence of these interventions. There were a total of 168 participants with probable Alzheimer's disease (AD) treated with donepezil. In the present article, the 21 participants with advanced AD who completed a follow-up period of 24 months are presented. The participants were grouped into three experimental groups (mindfulness, relaxation, and cognitive stimulation) and one control group. Each group carried out three weekly sessions with bi-annual follow-up measurements (cognition: CAMCOG and MMSE; functionality: RDRS; psychopathology: NPI). Non-parametric analyses were performed. The cognitive function and functionality scores showed no significant differences between the groups. However, the scores in cognitive function of the mindfulness group and the cognitive stimulation group did not decrease in an intra-group analysis. In NPI, there were significant differences between the mindfulness group and the control group by the end of the study (P<.017). The data showed that the treatment with donepezil in combination with mindfulness or cognitive stimulation presented a better clinical evolution than the pharmacological treatment alone or combined with relaxation. These data suggest that these therapeutic alternatives should be investigated further, and that the non-pharmacological treatments should be recommended in clinical practice in order to control the evolution of AD in the long term. In order to confirm these findings, a larger study is necessary. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

  9. Clinical and functional assessment of dysautonomia and its correlation in Alzheimer's disease.

    Science.gov (United States)

    Zakrzewska-Pniewska, Beata; Gawel, Malgorzata; Szmidt-Salkowska, Elzbieta; Kepczynska, Katarzyna; Nojszewska, Monika

    2012-12-01

    The aims were to assess dysautonomia in Alzheimer's Disease (AD), clinically and electrophysiologically, using sympathetic skin response (SSR) test and R-R interval variation (RRIV) test and to analyze the relationship between symptoms of dysautonomia and SSR/RRIV results. A tota of 54 patients with AD and 37 controls were evaluated using Autonomic Symptoms Questionnaire and SSR/RRIV test. Clinical dysautonomia was observed in 66% of patients (eg, orthostatic hypotension in 34.5%, constipation in 17.2%, urinary incontinence in 13.8%). The SSR test was abnormal in 26%, but the RRIV test was abnormal in 97.7% of cases; there was significant difference in RRIV test results between AD and controls (R mean 8.05% and 14.6%, respectively). In AD, clinical dysautonomia occurs at a various degree, and the abnormal SSR and RRIV test results were not always related to the presence of clinical dysautonomia; this observation points that the tests could be used as a useful tool in the assessment of subclinical dysautonomia.

  10. Alzheimer's disease.

    Science.gov (United States)

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

    2016-07-30

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

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

    International Nuclear Information System (INIS)

    Maruyama, Keiko; Ikeda, Shu-ichi; Yanagisawa, Nobuo.

    1995-01-01

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

  12. Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration.

    Science.gov (United States)

    Brenowitz, Willa D; Monsell, Sarah E; Schmitt, Frederick A; Kukull, Walter A; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively "pure" HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials.

  13. APOEε2 is associated with milder clinical and pathological Alzheimer's disease

    Science.gov (United States)

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

    2015-01-01

    Objective The Alzheimer disease (AD) APOEε4 risk allele associates with an earlier age of onset and increased amyloid-β deposition, whereas the protective APOEε2 allele delays the onset and appears to prevent amyloid-β deposition. Yet the clinical and pathological effects of APOEε2 remain uncertain because of its relative rarity. We investigated the effects of APOE ε2 and ε4 alleles on AD pathology and cognition in a large US dataset of well characterized AD patients. Methods We studied individuals from the National Alzheimer's Coordinating Center (NACC) autopsy cohort across the entire clinico-pathological continuum of AD. Multivariable models were built to examine the associations between APOE alleles and AD neuropathological changes, using the APOEε3/ε3 group as comparator. Mediation analysis was used to estimate the direct and indirect effects of APOE alleles on AD pathology and cognition (CDR-SOB and MMSE). Results Compared to APOEε3/ε3, APOEε2 is independently associated with lower Braak NFT stages and, possibly, fewer neuritic plaques, but has no direct effect on CAA severity, whereas APOEε4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage. Unadjusted analyses showed marked differences among APOE genotypes with respect to cognitive performance (ε2>ε3>ε4). Mediation analysis suggests that this is largely explained through effects on pathology. Interpretation Even when adjusted for age of onset, symptom duration and other demographic variables, APOEε2 is associated with milder AD pathology and less severe antemortem cognitive impairment compared to APOE ε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD. PMID:25623662

  14. Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults.

    Science.gov (United States)

    Gold, Brian T; Brown, Christopher A; Hakun, Jonathan G; Shaw, Leslie M; Trojanowski, John Q; Smith, Charles D

    2017-10-01

    Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer's disease (AD) pathology and cerebral white-matter hyperintensities (WMHs). Twenty-nine younger adults and 34 cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging was performed. Older adults further underwent lumbar cerebrospinal fluid draw for the assessment of AD pathology and FLAIR imaging for the assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked with lower levels of clinically silent AD pathology. In addition, AD pathology and WMHs were each independently related to increased functional magnetic resonance imaging response in the left dorsolateral prefrontal cortex, a pattern associated with slower task performance. Our results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance. Further, our findings suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Jagust, W.J.; Reed, B.R.; Seab, J.P.; Kramer, J.H.; Budinger, T.F.

    1989-01-01

    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer [ 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

  16. Stem Cell Therapy for Alzheimer's Disease: A Review of Recent Clinical Trials.

    Science.gov (United States)

    Kang, Jae Myeong; Yeon, Byeong Kil; Cho, Seong-Jin; Suh, Yoo-Hun

    2016-10-04

    Stem cell therapy has been noted to be a disease-modifying treatment for Alzheimer's disease (AD). After the failure to develop new drugs for AD, the number of studies on stem cells, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs), has increased from the early 2000 s. Issues pertaining to stem cells have been investigated in many animal studies in terms of stem cell origin, differentiation potency, method of culture, tumor formation, injection route, and mobility. Since 2010, mainly in East Asia, researchers began clinical trials investigating the use of stem cells for AD. Two phase I trials on moderate AD have been completed; though they revealed no severe acute or long-term side effects, no significant clinical efficacy was observed. Several studies, which involve more sophisticated study designs using different injection routes, well-established scales, and biomarkers such as amyloid positron emission tomography, are planned for mild to moderate AD patients. Here, we review the concept of stem cell therapy for AD and the progress of recent clinical trials.

  17. Deep Brain Stimulation for Alzheimer's Disease: Ethical Challenges for Clinical Research.

    Science.gov (United States)

    Siegel, Andrew M; Barrett, Marna S; Bhati, Mahendra T

    2017-01-01

    Deep brain stimulation (DBS) is an invasive neuromodulation modality that has shown early promise as a novel treatment of Alzheimer's disease (AD). Further clinical research is warranted on the basis of positive results from animal and human studies, as well as the inadequacy of existing treatments in reducing the enormous medical and financial costs of untreated AD. Nevertheless, unique ethical challenges require particular attention to elements of subject enrollment and informed consent. Study protocols should specify robust assessment and regular monitoring of subject decision-making capacity to consent to trial participation. Investigators should also assess for and mitigate therapeutic misconception (the phenomenon whereby a research participant conflates the goals of research with those of clinical treatment) and ensure that all prospective trial participants have adequate post-trial access to treatment and DBS device maintenance. In the following discussion, each issue is summarized and followed by recommendations for proper ethical procedure. We conclude by assimilating relevant ethical considerations into a decision-making algorithm designed to aid future clinical investigators of DBS for AD with the task of ethical subject enrollment.

  18. Re-Engineering Alzheimer Clinical Trials: Global Alzheimer’s Platform Network

    Science.gov (United States)

    Cummings, J.; Aisen, P.; Barton, R.; Bork, J.; Doody, R.; Dwyer, J.; Egan, J.C.; Feldman, H.; Lappin, D.; Truyen, L.; Salloway, S.; Sperling, R.; Vradenburg, G.

    2017-01-01

    Alzheimer’s disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer’s Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD. PMID:28459045

  19. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    Science.gov (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

    2015-11-01

    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. © 2015 Wiley Periodicals, Inc.

  20. Alzheimer's or Depression: Could It Be Both?

    Science.gov (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 ...

  1. Alzheimers sygdom

    DEFF Research Database (Denmark)

    Høgh, Peter

    2017-01-01

    Alzheimer's disease is a neurodegenerative disorder with insidious onset and slow progression. Prevalence is increasing, although not as fast as previously believed. The clinical diagnosis may be difficult, but diagnostic methods have been introduced and proven to be accurate in supporting...

  2. Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples.

    Science.gov (United States)

    Brenowitz, Willa D; Keene, C Dirk; Hawes, Stephen E; Hubbard, Rebecca A; Longstreth, W T; Woltjer, Randy L; Crane, Paul K; Larson, Eric B; Kukull, Walter A

    2017-05-01

    We examined the relationships between Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) in 2 large autopsy samples. Because findings may differ between study populations, data came from U.S. Alzheimer's Disease Centers contributing to the National Alzheimer's Coordinating Center (n = 2742) and from the population-based Adult Changes in Thought study (n = 499). Regardless of study population, over 50% of participants with ADNC had co-occurring LBD or VBI; the majority of whom had a clinical AD dementia diagnosis prior to death. Overlap of pathologies was similar between studies, especially after standardizing to the distribution of age and dementia status in the Adult Changes in Thought population. LBD, but not VBI, was positively associated with ADNC in both studies. Interestingly, cortical LBD was more common in those with intermediate ADNC compared to low or high ADNC, especially in the National Alzheimer's Coordinating Center (p < 0.001). High prevalence of co-occurring neuropathologies among older adults with dementia has implications for accurate diagnosis of dementia etiologies and development of disease-modifying strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. PREDICTORS OF PHYSICIAN REFERRAL FOR PATIENT RECRUITMENT TO ALZHEIMER DISEASE CLINICAL TRIALS

    Science.gov (United States)

    Galvin, James E.; Meuser, Thomas M.; Boise, Linda; Connell, Cathleen M

    2009-01-01

    Background Inadequate recruitment into Alzheimer disease (AD) clinical trials is an important threat to the validity and generalizability of the studies. The majority of dementia patients are first evaluated by community-based physicians; however, physician perceptions of clinical research are largely unknown. Methods A survey was distributed to 3,123 physicians in three states; 370 were returned. Survey items assessed attitudes, perceived benefits of and barriers to referral to clinical research and physicians use of the internet for medical information. Results The mean age of the respondents was 50.6 ± 10.8y; 70% were male, 78% Caucasian, 61% were primary care providers; 63% used the internet ≥3 times/week. No demographic or medical specialty differences existed between those who were likely (n=193) and unlikely (n=162) to refer patients to clinical trials. Differences were discovered in perceived benefits reported by physicians who were more likely to refer, while differences in perceived barriers existed in primary care compared with specialists. Referral to clinical trials is predicted by close proximity to a research center (OR:4.0,95%CI:1.1–15.6) and availability of internet information regarding diagnostic evaluation (OR:2.3,95%CI:1.1–4.7). Primary barriers included concerns about exposure of patients to uncomfortable procedures (OR:4.7,95%CI:1.2–18.7) and lack of time to discuss research participation (OR:6.8,95%CI:1.4–32.3). Conclusions Proximity to a research center and availability of diagnostic clinical tools are strong predictors of clinical trial referral. Concern over risks to patients and lack of time are strong barriers. These results suggest that dementia outreach education targeted to physicians should emphasize the importance of clinical trials with a focus on discussing research participation in a time-efficient manner and increasing awareness of risk reduction and the safety of research protocols. Providing easy access to up

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

    Science.gov (United States)

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

    2016-02-14

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

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

    Science.gov (United States)

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

    2014-03-01

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

  6. Alzheimer disease

    Science.gov (United States)

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

  7. Alzheimer's Association

    Science.gov (United States)

    ... will not share your information. * Required. View archives. Alzheimer's impact is growing Alzheimer's disease is the sixth- ... Last Updated: Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association advances research ...

  8. The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts.

    Science.gov (United States)

    Cano, Stefan J; Posner, Holly B; Moline, Margaret L; Hurt, Stephen W; Swartz, Jina; Hsu, Tim; Hobart, Jeremy C

    2010-12-01

    The Alzheimer's Disease Assessment Scale Cognitive Behavior Section (ADAS-cog), a measure of cognitive performance, has been used widely in Alzheimer's disease trials. Its key role in clinical trials should be supported by evidence that it is both clinically meaningful and scientifically sound. Its conceptual and neuropsychological underpinnings are well-considered, but its performance as an instrument of measurement has received less attention. Objective To examine the traditional psychometric properties of the ADAS-cog in a large sample of people with Alzheimer's disease. Data from three clinical trials of donepezil (Aricept) in mild-to-moderate Alzheimer's disease (n=1421; MMSE 10-26) were analysed at both the scale and component level. Five psychometric properties were examined using traditional psychometric methods. These methods of examination underpin upcoming Food and Drug Administration recommendations for patient rating scale evaluation. At the scale-level, criteria tested for data completeness, scaling assumptions (eg, component total correlations: 0.39-0.67), targeting (no floor or ceiling effects), reliability (eg, Cronbach's α: = 0.84; test-retest intraclass correlations: 0.93) and validity (correlation with MMSE: -0.63) were satisfied. At the component level, 7 of 11 ADAS-cog components had substantial ceiling effects (range 40-64%). Performance was satisfactory at the scale level, but most ADAS-cog components were too easy for many patients in this sample and did not reflect the expected depth and range of cognitive performance. The clinical implication of this finding is that the ADAS-cog's estimate of cognitive ability, and its potential ability to detect differences in cognitive performance under treatment, could be improved. However, because of the limitations of traditional psychometric methods, further evaluations would be desirable using additional rating scale analysis techniques to pinpoint specific improvements.

  9. A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease

    OpenAIRE

    Nascimento,Carla M. C.; Teixeira,Camila V. L.; Gobbi,Lilian T. B.; Gobbi,Sebastião; Stella,Florindo

    2012-01-01

    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 pati...

  10. [Effects of a neuropsychology program based on mindfulness on Alzheimer's disease: randomized double-blind clinical study].

    Science.gov (United States)

    Quintana Hernández, Domingo Jesús; Miró Barrachina, María Teresa; Ibáñez Fernández, Ignacio; del Pino, Angelo Santana; García Rodríguez, Javie r; Hernández, Jaime Rojas

    2014-01-01

    The purpose of this research was to assess effects of a mindfulness based neuropsychological intervention on the clinical course of Alzheimer's disease. A two year randomized and double blind clinical trial was conducted on 127 probable Alzheimer's disease patients, according to NINCDS-ADRDA scale. Patients were grouped into three experimental groups (cognitive stimulation, progressive muscular relaxation, and mindfulness) plus a control group. All participants were receiving donepezil. Cognitive skills were assessed with CAMCOG and MMSE, functional area with RDRS-2, and NPI was used for psychopathology screening. Three treatment sessions per week were carried out for two years, and follow up measurements were taken every six months. The global cognitive function, functionality and behavioral disorders measurements indicated that patients from the experimental group based on mindfulness were stable during the two years, while patients from the control group, as well as the other experimental groups, showed a mild but significant worsening of their mental capacities. The mindfulness based neuropsychological program showed better cognitive and functional stability, as well as significant improvement in the psychopathological condition of mild to moderate Alzheimer' patients. These results support the idea that a mindfulness based intervention can produce a clinically relevant improvement in the treatment of dementia. More research is needed to confirm these data. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

  11. Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Fernández-Matarrubia, Marta; Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Moreno-Ramos, Teresa; Valles-Salgado, María; Carreras, José Luis; Matías-Guiu, Jorge

    2018-01-01

    Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18 F fluorodeoxyglucose (FDG-PET). Forty-two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG-PET brain scan to provide data for voxel-based morphometric analysis. Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self-awareness in comparison with AD sample. Additionally, FDG-PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD. These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG-PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia.

    Science.gov (United States)

    Rajan, Kumar B; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Evans, Denis A

    2015-09-08

    To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1-0.9, 1.0-3.9, 4.0-6.9, 7.0-9.9, 10.0-12.9, and 13.0-17.9 years. Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0-17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1-0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established. © 2015 American Academy of Neurology.

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

    Directory of Open Access Journals (Sweden)

    Luísa eAlves

    2012-04-01

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

  14. Donepezil across the spectrum of Alzheimer's disease: dose optimization and clinical relevance.

    Science.gov (United States)

    Lee, J-H; Jeong, S-K; Kim, B C; Park, K W; Dash, A

    2015-05-01

    Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. AD is the most common cause of dementia worldwide, and its incidence is increasing in line with population aging. The primary feature of AD is progressive cognitive decline, and severe AD is characterized by reduced communication skills and mobility. However, successful treatment can substantially improve quality of life. Donepezil is an acetylcholinesterase inhibitor approved for use across the full spectrum of mild, moderate, and severe AD. Donepezil has been available at doses of 5 or 10 mg once daily for more than a decade and, more recently, a single high once-daily sustained-release 23-mg dose has been approved for treatment of patients with moderate to severe AD. The rationale for the higher dose formulation was the expected increase in acetylcholinesterase inhibition given the dose-response relationship of donepezil, with the benefits of the higher dose being most apparent in patients with more advanced AD. Donepezil 5 and 10 mg/day have been well studied in mild-to-moderate AD, and a clinical trial has confirmed the benefits of donepezil 23 mg/day in patients with moderate to severe AD, particularly for language and visuospatial ability. This review presents an overview of the evidence for donepezil across the spectrum of AD, with a focus on dose optimization for disease progression. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia

    Directory of Open Access Journals (Sweden)

    Florindo Stella

    Full Text Available Abstract In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD. Aims: To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods: This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years, with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain. Other psychopathological manifestations such as depression were also considered. Results: Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01, and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01. Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02, and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01. Conclusions: Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

  16. Mindfulness in the Maintenance of Cognitive Capacities in Alzheimer's Disease: A Randomized Clinical Trial.

    Science.gov (United States)

    Quintana-Hernández, Domingo J; Miró-Barrachina, María T; Ibáñez-Fernández, Ignacio J; Pino, Angelo Santana-Del; Quintana-Montesdeoca, María P; Rodríguez-de Vera, Bienvenida; Morales-Casanova, David; Pérez-Vieitez, María Del Carmen; Rodríguez-García, Javier; Bravo-Caraduje, Noelia

    2016-01-01

    The Canary Islands longitudinal study on non-pharmacological treatments showed the overall effectiveness of mindfulness in Alzheimer's disease (AD). However, no specific data on the maintenance of cognitive capacities were presented. To determine whether the practice of mindfulness modifies the course of cognitive impairment in AD. Longitudinal, non-inferiority and equivalence, randomized clinical trial, repeated-measures design, with three experimental groups and one control group. Patients with AD who voluntarily attended the Lidia García Foundation (n = 502). Only those who were treated with donepezil and MMSE ≥18 were included (n = 120). Over a two-year period, each group carried out three weekly sessions of stimulation based on mindfulness, cognitive stimulation therapy, and progressive muscle relaxation. Cognitive assessment CAMDEX-R (MMSE and CAMCOG). Repeated-measures ANOVA (p mindfulness group showed significant scores compared with the control and muscle relaxation groups (p mindfulness and cognitive stimulation therapy were equivalent (p≥0.05). Group cognitive stimulation evolved better than the control (p mindfulness group (p≥0.80), moderate for the relaxation group (p≥0.50), and low for the cognitive stimulation group (p≥0.20). The practice of mindfulness maintained cognitive function over a period of two years. This longitudinal study suggests that mindfulness can be used as a non-pharmacological treatment to slow cognitive impairment in AD.

  17. Huntington's disease and Huntington's disease-like syndromes: an overview.

    Science.gov (United States)

    Gövert, Felix; Schneider, Susanne A

    2013-08-01

    The differential diagnosis of chorea syndromes may be complex and includes various genetic disorders such as Huntington's disease and mimicking disorders called Huntington's disease-like (HDL) phenotypes. To familiarize clinicians with these (in some cases very rare) conditions we will summarize the main characteristics. HDL disorders are rare and account for about 1% of cases presenting with a Huntington's disease phenotype. They share overlapping clinical features, so making the diagnosis purely on clinical grounds may be challenging, however presence of certain characteristics may be a clue (e.g. prominent orofacial involvement in neuroferritinopathy etc.), Information of ethnic descent will also guide genetic work-up [HDL2 in Black Africans; dentatorubral-pallidoluysian atrophy (DRPLA) in Japanese etc.], Huntington's disease, the classical HDL disorders (except HDL3) and DRPLA are repeat disorders with anticipation effect and age-dependent phenotype in some, but genetic underpinnings may be more complicated in the other chorea syndromes. With advances in genetics more and more rare diseases are disentangled, allowing molecular diagnoses in a growing number of choreic patients. Hopefully, with better understanding of their pathophysiology we are moving towards mechanistic therapies.

  18. Predictors of placebo group decline in the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) in 24 week clinical trials of Alzheimer's disease.

    Science.gov (United States)

    Irizarry, Michael C; Webb, David J; Bains, Chanchal; Barrett, Steven J; Lai, Robert Y; Laroche, Janette P; Hosford, David; Maher-Edwards, Gareth; Weil, John G

    2008-07-01

    One limitation of several recent 24 week Alzheimer's disease (AD) clinical trials was the lack of cognitive decline detected by the AD Assessment Scale-cognitive subscale (ADAS-cog) in the placebo groups, possibly obscuring true medication effects. Data from 733 individuals in the placebo arms of six AD clinical trials performed 1996-1997 were pooled to examine the relationship of clinical, demographic, and genetic characteristics with the 24 week change in ADAS-cog. Baseline cognitive and functional status and the screening-to-baseline change in ADAS-cog were the strongest independent predictors of the 24 week change in ADAS-cog. The ADAS-cog did not detect progression in patients with mild dementia (screening Mini-Mental State Exam, MMSE, >or=20). The change in ADAS-cog from screening to baseline was inversely correlated with the 24 week change score; it was more difficult to detect cognitive decline at 24 weeks if individuals markedly worsened from screening to baseline. The effects of baseline MMSE and screening-to-baseline change in ADAS-cog generalized to the placebo group (N=106) of another AD study performed in 2004-2005. Overcoming lack of placebo decline in AD clinical trials will require scales more sensitive to cognitive decline in mild AD and strategies to reduce within-person variability in outcome measures.

  19. Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

    Science.gov (United States)

    Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih

    2015-11-25

    Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

  20. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  1. Advancing frontiers in Alzheimer's disease research

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  2. Low Prevalence and Clinical Effect of Vascular Risk Factors in Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Chen, Yaohua; Sillaire, Adeline Rollin; Dallongeville, Jean; Skrobala, Emilie; Wallon, David; Dubois, Bruno; Hannequin, Didier; Pasquier, Florence

    2017-01-01

    Determinants of early-onset Alzheimer's disease (EOAD) are not well known. In late-onset AD, vascular risk factors (VRFs) are associated with earlier clinical manifestation. The objective of this study was to assess the putative association between VRFs and EOAD. We studied participants with dementia meeting criteria for EOAD (recruited into the French CoMAJ prospective cohort study from 1 June 2009 to 28 February 2014) and age-, gender-matched controls (ratio 1:3, drawn randomly from the French MONA-LISA population-based survey between 2005 and 2007). Demographic data, VRFs, comorbidities, treatments, and APOE genotypes were compared in multivariable logistic regression analyses. We studied 102 participants with dementia (mean±standard deviation age: 59.5±3.8; women: 59.8%) and 306 controls. Compared with controls, EOAD participants had spent less time in formal education (9.9±2.9 versus 11.7±3.8 y; p < 0.0001), were less likely to be regular alcohol consumers (p < 0.0001), had a lower body mass index (-2 kg/m2; p < 0.0004), and a lower mean systolic blood pressure (-6.2 mmHg; p = 0.0036). The prevalence of APOE ɛ4 allele was higher in participants with dementia than in controls (50% versus 29.4%; p = 0.0002), as was the prevalence of depression (48% versus 32%; p < 0.001). Similar results were observed in multivariable analysis. Compared with EOAD participants lacking VRFs, EOAD participants with at least one VRF had a higher prevalence of depression (29.6% versus 53.3%, respectively; p = 0.03). The prevalence of VRFs is not elevated in EOAD patients (in contrast to older AD patients). Extensive genetic testing should be considered more frequently in the context of EOAD.

  3. Clinical Evaluation of Brain Perfusion SPECT with Brodmann Areas Mapping in Early Diagnosis of Alzheimer's Disease.

    Science.gov (United States)

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Fezoulidis, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2015-01-01

    Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

  4. A prospective study on the use of rivastigmine transdermal patch in Alzheimer's dementia in a routine clinical setting

    Directory of Open Access Journals (Sweden)

    Ejaz Nazir

    Full Text Available Abstract There is not much published literature on the use of rivastigmine patch in a "routine" clinical setting. Objectives: In this naturalistic longitudinal observational study we sought to evaluate the safety, tolerability and efficacy of the rivastigmine patch in patients with early and late onset moderate Alzheimer's disease in a routine clinical setting. Methods: Out of all routine clinical referrals, the first 30 patients with diagnosis of moderate Alzheimer's dementia who were started on rivastigmine patch were included in the study. Rivastigmine patch dose was titrated from 4.6 to 9.5 mg/ 24 hours as appropriate. The primary outcome measure was safety and tolerability, measured by the incidence of adverse events and discontinuation due to any reason. The secondary outcome measure was to examine improvement on global, functional and behavioral domains as demonstrated by the MMSE (Mini Mental State Examination score, BADLS (Bristol Activities of Daily Living Skills score, patient and carer feedback and clinical judgment. Results: Adverse events were reported in 20% of patients and 10% of total patients needed discontinuation of treatment. Improvement on global, functional and behavioral domains was observed in two thirds of patients whereas one third showed a relative decline. The most common side effect was skin irritation or erythema. Conclusions: The rivastigmine transdermal patch may provide a treatment option for those patients who require a change in their current oral cholinesterase inhibitor therapy due to safety or tolerability concerns.

  5. Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial.

    Science.gov (United States)

    Cummings, Jeffrey L; Lyketsos, Constantine G; Peskind, Elaine R; Porsteinsson, Anton P; Mintzer, Jacobo E; Scharre, Douglas W; De La Gandara, Jose E; Agronin, Marc; Davis, Charles S; Nguyen, Uyen; Shin, Paul; Tariot, Pierre N; Siffert, João

    Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking. To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation. Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed. In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60). The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]). A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo (ordinary least squares z statistic, -3.95; P Serious adverse events occurred in 7.9% with dextromethorphan-quinidine vs 4.7% with placebo. Dextromethorphan-quinidine was not associated with cognitive impairment, sedation, or clinically significant QTc prolongation. In this preliminary

  6. Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages

    NARCIS (Netherlands)

    Wu, Ying-Hui; Feenstra, Matthijs G. P.; Zhou, Jiang-Ning; Liu, Rong-Yu; Toranõ, Javier Sastre; van Kan, Hendrikus J. M.; Fischer, David F.; Ravid, Rivka; Swaab, Dick F.

    2003-01-01

    A disturbed sleep-wake rhythm is common in Alzheimer disease (AD) patients and correlated with decreased melatonin levels and a disrupted circadian melatonin rhythm. Melatonin levels in the cerebrospinal fluid are decreased during the progression of AD neuropathology (as determined by the Braak

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Alzheimer's Myths

    Science.gov (United States)

    ... home. Myth 3: Only older people can get Alzheimer's Reality: Alzheimer's can strike people in their 30s, ... Myth 7: Silver dental fillings increase risk of Alzheimer's disease Reality: According to the best available scientific ...

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

    Science.gov (United States)

    Cohen, Gene D.

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

  11. Selegiline for Alzheimer's disease.

    Science.gov (United States)

    Birks, J; Flicker, L

    2003-01-01

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

  12. Detecting Treatment Group Differences in Alzheimer's Disease Clinical Trials: A Comparison of Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating - Sum of Boxes (CDR-SB).

    Science.gov (United States)

    Wessels, A M; Dowsett, S A; Sims, J R

    2018-01-01

    The Alzheimer's Disease Assessment Scale's cognitive subscale (ADAS-Cog) has been widely used as an outcome measure in Alzheimer's Disease (AD) clinical trials. In its original form (ADAS-Cog11), the scale has been used successfully in mild-to-moderate AD dementia populations, but its use is more limited in the study of earlier disease (mild cognitive impairment [MCI] or mild dementia due to AD) owing to lack of appropriate sensitivity of some items. With recent focus on earlier treatment, efforts have focused on the development of more sensitive tools, including the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a global assessment tool to evaluate both cognition and function. The ability of the ADAS-Cog and CDR-SB to detect treatment group differences in the clinical trial environment has not been systematically studied. The aim of this analysis was to compare the utility of these tools in detecting treatment group differences, by reviewing study findings identified through advanced searches of clinicaltrials.gov and Ovid, and press releases and scientific presentations. Findings from placebo-controlled studies of ≥ 6m duration and enrolling >100 participants were included; reporting of both the ADAS-Cog and CDR-SB at endpoint was also a requirement. Of the >300 records identified, 34 studies fulfilled the criteria. There were significant placebo versus active drug group differences based on findings from at least one measure for 14 studies. The ADAS-Cog detected treatment differences more frequently than the CDR-SB. Based on these and previously published findings, the ADAS-Cog appears more useful than the CDR-SB in detecting treatment group differences.

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

    Directory of Open Access Journals (Sweden)

    Jones Roy

    2011-10-01

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

  14. Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design.

    Science.gov (United States)

    Qian, Jing; Hyman, Bradley T; Betensky, Rebecca A

    2017-05-01

    The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging's Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = -0.19; P trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89% power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage

  15. Knowledge on Alzheimer's Disease among Public Hospitals and Health Clinics Pharmacists in the State of Selangor, Malaysia.

    Science.gov (United States)

    Mat Nuri, Thimarul Huda; Hong, Yet Hoi; Ming, Long Chiau; Mohd Joffry, Suhaidah; Othman, Muhamad Faiz; Neoh, Chin Fen

    2017-01-01

    The prevalence of Alzheimer's disease (AD) has increased with the fast growing of aging population, thereby posing great challenges to provision of care for AD patients. Pharmacists play a vital role in the management of AD; this includes recognizing early symptoms of AD, providing medication counseling to AD patients and their caretakers, and identifying potential adverse drug reactions. A comprehensive understanding of the disease progression, as well as the pharmacological therapy, is essential to provide effective care to AD patients. The level of knowledge about AD among the pharmacists, however, remains unknown. Hence, this study aimed to assess the knowledge on AD among the pharmacists in public hospitals and health clinics and its correlates. A clear picture of the characteristics associated with different levels of knowledge could facilitate the targeted re-training of pharmacists. The 30-item validated Alzheimer disease knowledge scale (ADKS) tool was pilot-tested and used in this cross-sectional study. All pharmacists, from nine public hospitals and seven public health clinics in the State of Selangor, Malaysia, were invited to participate in this cross-sectional survey. The ADKS score was computed and compared across demographics characteristics. A total of 445 pharmacists responded to the survey. These pharmacists had a moderate overall score in ADKS; nevertheless, high scores were recorded in the domains of treatment management and care giving. No difference in AD knowledge was found among pharmacists worked in public hospitals and health clinics, except for the domain of care giving ( p = 0.033). Ethnicity and age group were independent predictors of ADKS score in the current study. The pharmacists in the current study had moderate AD knowledge. On-going education and training programme on AD, in particular the domains other than treatment management and care giving, should be provided to the pharmacists to ensure delivery of quality care to AD

  16. Knowledge on Alzheimer's Disease among Public Hospitals and Health Clinics Pharmacists in the State of Selangor, Malaysia

    Directory of Open Access Journals (Sweden)

    Thimarul Huda Mat Nuri

    2017-10-01

    Full Text Available The prevalence of Alzheimer's disease (AD has increased with the fast growing of aging population, thereby posing great challenges to provision of care for AD patients. Pharmacists play a vital role in the management of AD; this includes recognizing early symptoms of AD, providing medication counseling to AD patients and their caretakers, and identifying potential adverse drug reactions. A comprehensive understanding of the disease progression, as well as the pharmacological therapy, is essential to provide effective care to AD patients. The level of knowledge about AD among the pharmacists, however, remains unknown. Hence, this study aimed to assess the knowledge on AD among the pharmacists in public hospitals and health clinics and its correlates. A clear picture of the characteristics associated with different levels of knowledge could facilitate the targeted re-training of pharmacists. The 30-item validated Alzheimer disease knowledge scale (ADKS tool was pilot-tested and used in this cross-sectional study. All pharmacists, from nine public hospitals and seven public health clinics in the State of Selangor, Malaysia, were invited to participate in this cross-sectional survey. The ADKS score was computed and compared across demographics characteristics. A total of 445 pharmacists responded to the survey. These pharmacists had a moderate overall score in ADKS; nevertheless, high scores were recorded in the domains of treatment management and care giving. No difference in AD knowledge was found among pharmacists worked in public hospitals and health clinics, except for the domain of care giving (p = 0.033. Ethnicity and age group were independent predictors of ADKS score in the current study. The pharmacists in the current study had moderate AD knowledge. On-going education and training programme on AD, in particular the domains other than treatment management and care giving, should be provided to the pharmacists to ensure delivery of quality

  17. Iterative Image Processing for Early Diagnostic of Beta-Amyloid Plaque Deposition in Pre-Clinical Alzheimer's Disease Studies.

    Science.gov (United States)

    Slavine, Nikolai V; Kulkarni, Padmakar V; McColl, Roderick W

    2017-08-01

    To test and evaluate an efficient iterative image processing strategy to improve the quality of sub-optimal pre-clinical PET images. A novel iterative resolution subsets-based method to reduce noise and enhance resolution (RSEMD) has been demonstrated on examples of PET imaging studies of Alzheimer's disease (AD) plaques deposition in mice brains. The RSEMD method was applied to imaging studies of non-invasive detection of beta-amyloid plaque in transgenic mouse models of AD. Data acquisition utilized a Siemens Inveon® micro PET/CT device. Quantitative uptake of the tracer in control and AD mice brains was determined by counting the extent of plaque deposition by histological staining. The pre-clinical imaging software inviCRO ® was used for fitting the recovery PET images to the mouse brain atlas and obtaining the time activity curves (TAC) from different brain areas. In all of the AD studies the post-processed images proved to have higher resolution and lower noise as compared with images reconstructed by conventional OSEM method. In general, the values of SNR reached a plateau at around 10 iterations with an improvement factor of about 2 over sub-optimal PET brain images. A rapidly converging, iterative deconvolution image processing algorithm with a resolution subsets-based approach RSEMD has been used for quantitative studies of changes in Alzheimer's pathology over time. The RSEMD method can be applied to sub-optimal clinical PET brain images to improve image quality to diagnostically acceptable levels and will be crucial in order to facilitate diagnosis of AD progression at the earliest stages.

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

    Science.gov (United States)

    Poncet, Michel

    2011-09-01

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

  19. Does the Interplay Between Aging and Neuroinflammation Modulate Alzheimer's Disease Clinical Phenotypes? A Clinico-Pathological Perspective.

    Science.gov (United States)

    Taipa, Ricardo; Sousa, Ana Luísa; Melo Pires, Manuel; Sousa, Nuno

    2016-05-11

    Alzheimer's disease (AD) is a chronic neurodegenerative disorder and is the most common cause of dementia worldwide. Cumulative data suggests that neuroinflammation plays a prominent and early role in AD, and there is compelling data from different research groups of age-associated dysregulation of the neuroimmune system. From the clinical point of view, despite clinical resemblance and neuropathological findings, there are important differences between the group of patients with sporadic early-onset (65 years old). Thus, it seems important to understand the age-dependent relationship between neuroinflammation and the underlying biology of AD in order to identify potential explanations for clinical heterogeneity, interpret biomarkers, and promote the best treatment to different clinical AD phenotypes. The study of the delicate balance between pro-inflammatory or anti-inflammatory sides of immune players in the different ages of onset of AD would be important to understand treatment efficacy in clinical trials and eventually, not only direct treatment to early disease stages, but also the possibility of establishing different treatment approaches depending on the age of the patient. In this review, we would like to summarize what is currently known about the interplay between "normal" age associated inflammatory changes and AD pathological mechanisms, and also the potential differences between early-onset and late-onset AD taking into account the age-related neuroimmune background at disease onset.

  20. The association between APOE ε4 and Alzheimer-type dementia among memory clinic patients is confined to those with a higher education. The DESCRIPA Study.

    Science.gov (United States)

    Vermeiren, Angelique P A; Bosma, Hans; Visser, Pieter-Jelle; Zeegers, Maurice P; Graff, Caroline; Ewers, Michael; Frisoni, Giovanni B; Frölich, Lutz; Hampel, Harald; Jones, Roy W; Kehoe, Patrick G; Lenoir, Hermine; Minthon, Lennart; Nobili, Flavio M; Olde Rikkert, Marcel; Rigaud, Anne-Sophie; Scheltens, Philip; Soininen, Hilkka; Spiru, Luiza; Tsolaki, Magda; Wahlund, Lars-Olof; Vellas, Bruno; Wilcock, Gordon; Elias-Sonnenschein, Lyzel S; Verhey, Frans R J

    2013-01-01

    We assessed the interaction between the APOE ε4 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 age, gender, and center. APOE ε4 predicted the onset of AD-type dementia in middle (HR 3.45 95% CI 1.79-6.65, n = 222) and high (HR 3.67 95% CI 1.36-9.89, n = 139) but not in low educated subjects (HR 0.81, 95% CI 0.38-1.72, n = 183). This suggests that mechanisms in developing Alzheimer-type dementia may differ between educational groups that raises questions related to Alzheimer-type dementia prevention.

  1. Clinical significance of determination of plasma ET and serum folic acid, vitamin B12 levels in patients with alzheimer diseases (AD)

    International Nuclear Information System (INIS)

    Shi Hongchao; Wang Jun; Jiang Jiandong

    2007-01-01

    Objective: To explore the clinical significance of changes of plasma endothelin(ET) and folic acid and Vitamin B 12 (VitB 12 ) levels in patients with Alzheimer diseases. Methods: Plasma levels of ET was determined with RIA and serum levels of Folic acid. VitaminB 12 were measured by automated chemiluminescence system in 41 patients with Alzheimer disease and 35 controls. Results: The plasma ET levels in the patients were significantly higher than those in controls (P 12 levels were significantly lower (P 12 levels were mutually negatively correlated (r=-0.6018, -0.7124, P 12 levels was helpful for the prediction of treatment efficacy in patients with Alzheimer disease. (authors)

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

    Science.gov (United States)

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

  3. Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF biomarkers.

    Science.gov (United States)

    Vercruysse, Olivier; Paquet, Claire; Gabelle, Audrey; Delbeuck, Xavier; Blanc, Frederic; Wallon, David; Dumurgier, Julien; Magnin, Eloi; Martinaud, Olivier; Jung, Barbara; Bousiges, Olivier; Lehmann, Sylvain; Delaby, Constance; Quillard-Murain, Muriel; Peoc'h, Katell; Laplanche, Jean-Louis; Bouaziz-Amar, Elodie; Hannequin, Didier; Sablonniere, Bernard; Buee, Luc; Hugon, Jacques; Schraen, Susanna; Pasquier, Florence; Bombois, Stephanie

    2018-01-09

    Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). The aim of this study was to test the hypothesis of misdiagnoses for these patients. Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF A1-42, T-tau and P-tau biomarkers and clinical follow-up, were included. Clinical and imaging data were reviewed by an independent board, from baseline (visit with clinical evaluation and CSF analysis) to the end of the follow-up, for a final diagnosis. In the e-PLM cohort of 1098 AD patients with CSF analysis, 37 (3.3%) patients (20 with AD dementia core clinical criteria and 17 with AD-MCI core clinical criteria) had normal CSF biomarker profile and a clinical follow-up. All patients presented with episodic memory impairment and 27 (73%) had medial temporal lobe atrophy on MRI-scan. After a median follow-up of 36 months (range 7-74), the final diagnosis was AD MCI or dementia for 9 (24%) patients, and unlikely due to AD for 28 (76%) patients. A misdiagnosis was corrected in 18 (49%) patients (mood disorders, non-AD degenerative dementia, vascular cognitive impairment, alcohol cognitive disorders, temporal epilepsy and hippocampal sclerosis), and 10 (27%) patients had cognitive disorders of undetermined etiology. AD diagnosis (MCI or dementia) with normal CSF biomarkers is a rare condition. A clinical follow-up is particularly recommended to consider an alternative diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Igor O Korolev

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

  6. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

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

    2011-01-01

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

  7. Neuroinflammation in Alzheimer's disease wanes with age

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Bowen, D.M.; Neary, D.; Sims, N.R.; Snowden, J.S.

    1986-01-01

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

  9. Biomarkers in clinical trials of Alzheimer disease (AD): what is expected from regulatory agencies?

    Science.gov (United States)

    Sampaio, C

    2009-04-01

    Biomarkers are key for the different phases of drug development in Alzheimer Disease and in other fields. Traditionally the process of biomarker qualification has been slow, mostly exclusively academic. Regulators were mostly passive spectators. The Pharmaceutical innovation crisis of the end of XX century prompted the regulatory agencies and the governments from both sides of the Atlantic to initiate a number of programs to foster renovation, creativity and new paradigms. This created the opportunity for regulators to move from a passive position to a more active role, as facilitators. However, it is becoming apparent that there is room for even more central roles for regulators in the interactive consortia that are now in place. It is also becoming apparent that regulatory agencies are expected to become highly specialized hubs holding expert "know-how" not easily available elsewhere.

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

    Directory of Open Access Journals (Sweden)

    Angela Altomare

    2014-11-01

    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.

  11. New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials.

    Science.gov (United States)

    Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

    2015-11-12

    As currently used, the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer's disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity. Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect. The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect. The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer's disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.

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

    Directory of Open Access Journals (Sweden)

    Farid Fadaei

    2007-04-01

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

  13. Alzheimer's: Glossary

    Science.gov (United States)

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

  14. Understanding Alzheimer's

    Science.gov (United States)

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

  15. Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease.

    Science.gov (United States)

    Qian, Winnie; Fischer, Corinne E; Schweizer, Tom A; Munoz, David G

    2018-01-01

    Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis. Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction. Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the

  16. Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.

    Science.gov (United States)

    Yang, Wen-Ting; Zheng, Xia-Wei; Chen, Shuang; Shan, Chun-Shuo; Xu, Qing-Qing; Zhu, Jia-Zhen; Bao, Xiao-Yi; Lin, Yan; Zheng, Guo-Qing; Wang, Yan

    2017-10-01

    Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Science.gov (United States)

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

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

    DEFF Research Database (Denmark)

    Carrasco, J; Adlard, P; Cotman, C

    2006-01-01

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

  19. Clinical psychological tests useful for differentiating depressive state with Alzheimer's disease from major depression of the elderly.

    Science.gov (United States)

    Hattori, Hideyuki; Yoshiyama, Kenji; Miura, Rina; Fujie, Sachiko

    2010-03-01

    A depressive state with Alzheimer's disease (AD) is difficult to differentiate from major depression (MD) in many cases. The purpose of this study was to identify differences between the two disorders using a battery of clinically available psychological tests. We evaluated depression and apathy using the Geriatric Depression Scale consisting of 30 items (GDS30) and Apathy Scale in 38 patients with AD and 31 with MD who were diagnosed based on clinical symptoms and radiological findings. In addition, the Cornel Medical Index (CMI) was employed to compare the psychological features of the two disorders. In AD patients, the Apathy Scale score was greater than the GDS30 score, suggesting a strong tendency toward apathy. There was a significant difference in the GDS30/Apathy Scale score ratio between the two groups (P depression-category parameters were significantly higher in MD patients. In individual patients, we compared the scores for the two categories, and there was a marked difference (P < 0.001, OR: 10.6). These results suggest that the GDS30, Apathy Scale, and CMI are useful for differentiating MD from AD and evaluating their psychological features.

  20. Clinical Trials for Disease-Modifying Therapies in Alzheimer's Disease: A Primer, Lessons Learned, and a Blueprint for the Future.

    Science.gov (United States)

    Cummings, Jeffrey; Ritter, Aaron; Zhong, Kate

    2018-03-16

    Alzheimer's disease (AD) has no currently approved disease-modifying therapies (DMTs), and treatments to prevent, delay the onset, or slow the progression are urgently needed. A delay of 5 years if available by 2025 would decrease the total number of patients with AD by 50% in 2050. To meet the definition of DMT, an agent must produce an enduring change in the course of AD; clinical trials of DMTs have the goal of demonstrating this effect. AD drug discovery entails target identification followed by high throughput screening and lead optimization of drug-like compounds. Once an optimized agent is available and has been assessed for efficacy and toxicity in animals, it progresses through Phase I testing with healthy volunteers, Phase II learning trials to establish proof-of-mechanism and dose, and Phase III confirmatory trials to demonstrate efficacy and safety in larger populations. Phase III is followed by Food and Drug Administration review and, if appropriate, market access. Trial populations include cognitively normal at-risk participants in prevention trials, mildly impaired participants with biomarker evidence of AD in prodromal AD trials, and subjects with cognitive and functional impairment in AD dementia trials. Biomarkers are critical in trials of DMTs, assisting in participant characterization and diagnosis, target engagement and proof-of-pharmacology, demonstration of disease-modification, and monitoring side effects. Clinical trial designs include randomized, parallel group; delayed start; staggered withdrawal; and adaptive. Lessons learned from completed trials inform future trials and increase the likelihood of success.

  1. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

    Science.gov (United States)

    Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

    2012-04-01

    We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Clock drawing test in screening for Alzheimer's dementia and mild cognitive impairment in clinical practice.

    Science.gov (United States)

    Vyhnálek, Martin; Rubínová, Eva; Marková, Hana; Nikolai, Tomáš; Laczó, Jan; Andel, Ross; Hort, Jakub

    2017-09-01

    The clock drawing test (CDT) is a commonly used brief cognitive measure. We evaluated diagnostic accuracy of subjective ratings of CDT by physicians (with/without specialty in cognitive neurology) and neuropsychologists in discriminating amnestic mild cognitive impairment (aMCI), Alzheimer's dementia (AD) and cognitively healthy older adults. We further compared the diagnostic accuracy of subjective categorical ratings with complex scoring of CDT. Three cognitive neurologists, three neuropsychologists and six neurology residents without experience in cognitive neurology blinded to the diagnosis rated 187 CDTs (50 mild AD, 49 aMCI and 88 cognitively healthy older adults) using a "yes" (abnormal) versus "suspected" versus "no" (normal) classification. The rating suspected was combined with yes or no to obtain two sets of sensitivity estimates. We also used a 17-point CDT rating system. When using the categorical rating, neuropsychologists had highest sensitivity (89%) in differentiating patients with mild AD (yes/suspected versus no), followed by neurologic residents (80%) and cognitive neurologists (79%). When differentiating patients with aMCI (yes/suspected versus no), the sensitivity was 84% for neuropsychologists, 64% for cognitive neurologists and 62% for residents. The sensitivity using the complex scoring system was 92% in patients with mild AD and 69% in patients with aMCI. A categorical rating of CDT shows high sensitivity for mild AD even in non-experienced raters. Neuropsychologists outperformed physicians in differentiating patients with aMCI from cognitively healthy older adults (specificity), which was counterbalanced by the lower specificity of their ratings. The diagnostic accuracy was not substantially improved by using complex scoring system. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Methodological challenges in assessing the impact of comorbidities on costs in Alzheimer's disease clinical trials.

    Science.gov (United States)

    Kahle-Wrobleski, Kristin; Fillit, Howard; Kurlander, Jonathan; Reed, Catherine; Belger, Mark

    2015-12-01

    Alzheimer's disease (AD) is associated with considerable costs and has a significant impact on health and social care systems. This study assessed whether baseline comorbidities present in 2,594 patients with AD participating in two semagacestat randomized placebo-controlled trials (RCTs) would significantly impact overall costs. Resource utilization was captured using the Resource Utilization in Dementia Scale-Lite. Comorbidities and concomitant medications were tabulated via patient and caregiver reports. Only baseline data were analyzed. Direct and indirect costs per month were calculated per patient. The relationship between cost and explanatory variables was explored in a regression model. The baseline monthly cost of care in this RCT population was £1,147 ± 2,483, with informal care costs accounting for 75% of costs. Gender, age, and functional status were significant predictors of costs (p ≤ 0.0001). The cost ratio was not impacted when the number of comorbidities was added to the model (cost ratio = 0.95; 95% CI 0.91-0.99) or when combined with the number of concomitant medications (cost ratio = 0.97; 95% CI 0.95-1.00). Inconsistent findings related to the impact of individual comorbidities on costs were noted in sensitivity analyses. The number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because RCTs often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for AD.

  4. [Calcium hypothesis of Alzheimer disease].

    Science.gov (United States)

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

    2012-01-01

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

  5. Comparisons of clinical symptoms in biomarker-confirmed Alzheimer's disease, dementia with Lewy bodies, and frontotemporal dementia patients in a local memory clinic.

    Science.gov (United States)

    Shea, Yat Fung; Ha, Joyce; Chu, Leung-Wing

    2015-12-01

    There has been no previous Chinese study that differentiated the clinical symptoms among biomarker-confirmed Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). The objective of this study was to compare the cognitive, behavioural, and neuropsychiatric symptoms in biomarker-confirmed AD, DLB, and FTD patients. We recruited 30 patients (14 AD, 7 DLB, 9 FTD) who presented to the memory clinic at Queen Mary Hospital from 1 January 2007 to 31 December 2013. AD was diagnosed according to the National Institution of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria with cerebrospinal fluid biomarkers (tau, phosphorylated tau, and amyloid β-42) fulfilling locally determined cut-off values for AD. DLB was diagnosed based on the McKeith diagnostic criteria. The behavioural variant of FTD was diagnosed based on the revised diagnostic criteria proposed by the International bvFTD Criteria Consortium, and language variant FTD was diagnosed based on the latest published criteria. In addition, patients with DLB and FTD had typical imaging features on single-photon emission computed tomography or (18) fludeoxyglucose-positron emission tomography, either with or without Pittsburgh Compound B imaging, which supported their diagnoses. Data on patient characteristics including demographics, presenting clinical features, Mini-Mental State Examination, clinical dementia ratings, and neuropsychiatry inventory scores were collected. There were no differences in age, education level, dementia severity, and duration of symptoms before presentation among the three subgroups of patients. All patients had amnesia symptoms, which were not statistically significant. Apraxia was most common in AD. While 83% of the patients were affected by behavioural and neuropsychiatric symptoms of dementia, behavioural disinhibition and decline in executive function were most common in FTD

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

    NARCIS (Netherlands)

    J.J. Claus (Jules Johan)

    1993-01-01

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

  7. CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts.

    Science.gov (United States)

    Hansson, Oskar; Seibyl, John; Stomrud, Erik; Zetterberg, Henrik; Trojanowski, John Q; Bittner, Tobias; Lifke, Valeria; Corradini, Veronika; Eichenlaub, Udo; Batrla, Richard; Buck, Katharina; Zink, Katharina; Rabe, Christina; Blennow, Kaj; Shaw, Leslie M

    2018-03-01

    We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Cutoffs for Elecsys amyloid-β 1-42 (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [ 18 F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [ 18 F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. CSF total tau/Aβ(1-42) and phosphorylated tau/Aβ(1-42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%-90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read-based outcomes. Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

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

  9. WITHDRAWN: Tacrine for Alzheimer's disease.

    Science.gov (United States)

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

    2007-07-18

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

  10. Efficacy of Memantine, Donepezil, or Their Association in Moderate-Severe Alzheimer's Disease: A Review of Clinical Trials

    Science.gov (United States)

    Molino, Ivana; Colucci, Luisa; Fasanaro, Angiola M.

    2013-01-01

    Background. Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage. Objectives. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD. Method. Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007–2012. Results and Conclusion. Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of “adequacy and representativeness.” Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials. PMID:24288512

  11. High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment.

    Science.gov (United States)

    Eckerström, Marie; Berg, Anne Ingeborg; Nordlund, Arto; Rolstad, Sindre; Sacuiu, Simona; Wallin, Anders

    2016-01-01

    Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI. © 2016 S. Karger AG, Basel.

  12. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China: A multicenter survey from 2011 to 2014.

    Science.gov (United States)

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

    2016-06-01

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

  13. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan.

    Science.gov (United States)

    Montgomery, William; Ueda, Kaname; Jorgensen, Margaret; Stathis, Shari; Cheng, Yuanyuan; Nakamura, Tomomi

    2018-01-01

    The burden of dementia in Japan is large and growing. With the world's fastest aging population, it is estimated that one in five elderly people will be living with dementia in Japan by 2025. The most common form of dementia is Alzheimer's disease (AD), accounting for around two-thirds of dementia cases. A systematic review was conducted to examine the epidemiology and associated burden of AD in Japan and to identify how AD is diagnosed and managed in Japan. English and Japanese language databases were searched for articles published between January 2000 and November 2015. Relevant Japanese sources, clinical practice guideline registers, and reference lists were also searched. Systematic reviews and cohort and case-control studies were eligible for inclusion, with a total of 60 studies included. The most recent national survey conducted in six regions of Japan reported the mean prevalence of dementia in people aged ≥65 years to be 15.75% (95% CI: 12.4, 22.2%), which is much higher than the previous estimated rate of 10% in 2010. AD was confirmed as the predominant type of dementia, accounting for 65.8% of all cases. Advancing age and low education were the most consistently reported risk factors for AD dementia. Japanese guidelines for the management of dementia were released in 2010 providing specific guidance for AD about clinical signs, image findings, biochemical markers, and treatment approaches. Pharmacotherapies and non-pharmacotherapies to relieve cognitive symptoms were introduced, as were recommendations to achieve better patient care. No studies reporting treatment patterns were identified. Due to population aging and growing awareness of AD in Japan, health care expenditure and associated burden are expected to soar. This review highlights the importance of early detection, diagnosis, and treatment of AD as strategies to minimize the impact of AD on society in Japan.

  14. The Effect of Participation in Support Groups on Depression, Anxiety and Stress in Family Caregivers of People with Alzheimers: Randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Fahimeh Taati

    2016-07-01

    Full Text Available This study sought to determine the effect of participation in support groups on the depression, anxiety and stress level of caregivers of patients with Alzheimer. This study was a single blind randomized clinical controlled trial (RCT with 80 family caregivers of people with Alzheimer’s (per group=40. The intervention group participated in eight sessions 1.5- 2 hours in support groups. The tool used in this study was the DASS-21 questionnaire for measuring depression, anxiety and stress level of the caregivers, analysis of parametric data, using SPSS version 21. Findings showed, participation in support groups showed no significant difference on depression, anxiety and stress in family caregivers of Alzheimer patients in the control group and the intervention group. Given that caring for these patients by their family members are very sensitive and costly issues for policy makers and health service providers, community and families of these patients.

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

    DEFF Research Database (Denmark)

    Wilkinson, David; Schindler, Rachel; Schwam, Elias

    2009-01-01

    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...

  16. Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: implications for clinical trials in Alzheimer's disease.

    Science.gov (United States)

    Savory, J; Huang, Y; Wills, M R; Herman, M M

    1998-04-01

    A clinical trial in patients with Alzheimer's disease has indicated that frequent intramuscular (i.m.) treatment with desferrioxamine (DFO) slows progression of the disease. Confirmatory trials have not been carried out, partly because of the rigors of twice daily intramuscular injections over a period of 2 years, even though the initial report gave promising results. The aim of the present study was to determine an optimal DFO treatment protocol in an animal model exhibiting Alzheimer's-like intraneuronal protein aggregates, previously shown to be partially reversed by such treatment. New Zealand white rabbits were injected intracisternally with either aluminum (Al) maltolate or with saline on day 0. Intramuscular injections of DFO were given to selected rabbits for 2 days prior to sacrifice on days 4, 6 or 8. Bielschowsky's silver impregnation demonstrated widespread neurofibrillary degeneration (NFD) in neuronal cell bodies and neurites of brain and spinal cord from Al-treated rabbits. Monoclonal antibodies Tau-2, AT8, PHF-1 and Alz-50, all of which characteristically stain neurofibrillary tangles associated with Alzheimer's disease, strongly labeled the Al-induced NFD. The number of positive neurons and staining intensities were much less in rabbits treated with Al and subsequently with DFO, than in animals only given Al. Control rabbit receiving intracisternal saline were negative for NFD. The results of quantitative immunohistochemistry using image analysis confirmed that immunostaining densities with all tau mAbs were higher in Al-treated than in Al-DFO-treated or in saline-treated controls. Furthermore, it appears that hyperphosphorylation of tau does not make this protein resistant to degradation once Al has been removed by DFO treatment. The effectiveness of only two days of DFO treatment in reversing Al-induced neurofibrillary degeneration suggests that further clinical trials of DFO for treatment of Alzheimer's disease should be attempted using much

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

    OpenAIRE

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

    2016-01-01

    Detecting at-risk individuals within a healthy population is critical for preventing or delaying Alzheimer?s disease. The systems biology integration of brain and body metabolism enables peripheral metabolic biomarkers to serve as reporters of brain bioenergetic status. Using clinical metabolic data derived from healthy postmenopausal women in the ELITE trial, we conducted principal components and k-means clustering analyses of nine biomarkers to define metabolic phenotypes. Metabolic cluster...

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

    Directory of Open Access Journals (Sweden)

    Mateus Rocha de Paula

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

  19. The clinical utility of informants' appraisals on prospective and retrospective memory in patients with early Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Yen-Hsuan Hsu

    Full Text Available Increasing studies suggest the importance of including prospective memory measures in clinical evaluation of dementia due to its sensitivity and functional relevance. The Prospective and Retrospective Memory Questionnaire (PRQM is originally a self-rated memory inventory that offers a direct comparison between prospective and episodic memory. However, the informant's report has been recognized as a more valid source of cognitive complaints. We thus aimed to examine the validity of the informant-rated form of the PRMQ in assessing memory function of the patients and in detecting individuals with early dementia. The informants of 140 neurological outpatients with memory complaints completed the Taiwan version of the PRMQ. Tests of prospective memory, short-term memory, and general cognitive ability were also administered to non-demented participants and patients with early stages of Alzheimer's disease (AD. Results showed significant relationships between the PRMQ ratings and objective cognitive measures, and showed that higher ratings on the PRMQ were associated with increasing odds of greater dementia severity. Receiver operative characteristic (ROC curves showed an adequate ability of the PRMQ to identify patients with dementia (93% sensitivity and 84% specificity. Hierarchical regression revealed that the PRMQ has additional explanatory power for dementia status after controlling for age, education and objective memory test results, and that the prospective memory subscale owns predictive value for dementia beyond the retrospective memory subscale. The present study demonstrated the external validity and diagnostic value of informants' evaluation of their respective patients' prospective and retrospective memory functioning, and highlighted the important role of prospective memory in early dementia detection. The proxy-version of the PRMQ is a useful tool that captures prospective and episodic memory problems in patients with early AD, in

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

    Science.gov (United States)

    Rocha de Paula, Mateus; Gómez Ravetti, Martín; Berretta, Regina; Moscato, Pablo

    2011-03-24

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  2. Immunterapi mod Alzheimers sygdom

    DEFF Research Database (Denmark)

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-01

    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...

  3. Urinary incontinence in Alzheimer's disease is associated with Clinical Dementia Rating-Sum of Boxes and Barthel Activities of Daily Living.

    Science.gov (United States)

    Na, Hae Ri; Park, Moon Ho; Cho, Sung Tae; Lee, Byung Chul; Park, Suyeol; Kim, Khae Hawn; Choi, Jong Bo

    2015-03-01

    Urinary incontinence (UI) and Alzheimer's disease (AD) are common in the elderly population and have increased rapidly in recent decades. This study aimed to evaluate the prevalence of UI and determine the neuropsychological characteristics of patients with AD and UI. A total of 464 patients with probable AD were recruited, and the prevalence and type of UI were evaluated. Neuropsychological evaluation was assessed using the Mini-Mental Status Examination, Clinical Dementia Rating, Clinical Dementia Rating-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living and Instrumental Activities of Daily Living. The prevalence of UI in patients with AD was 24.8% (men 29.6%, women 23.0%). The two most common types of UI were urge incontinence (44.3%) and functional incontinence (25.3%). UI in patients with Alzheimer's disease was statistically significantly associated with Clinical Dementia Rating-Sum of Boxes (OR 1.56, 95% CI 1.21-2.01) and Barthel Activities of Daily Living (OR 1.34, 95%CI 1.22-1.47) after adjustment for different covariates. UI commonly occurred in patients with AD. The Clinical Dementia Rating-Sum of Boxes and Barthel Activities of Daily Living could be potential predictors for UI in patients with AD. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

  4. Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of Change Observed.

    Science.gov (United States)

    Lacey, Loretto; Bobula, Joel; Niecko, Timothy; Leibman, Christopher

    2017-06-01

    We evaluate the association between caregiver (informal) time/cost and illness severity from two recently completed clinical trials of an investigational drug for Alzheimer's disease (AD). Changes from baseline caregiver time were calculated and treatment effects analyzed using a restricted maximum likelihood-based mixed model for repeated measures. Four separate models were then estimated to examine the association between caregiver time costs and the clinical endpoints measured during the trials, including cognition (MMSE), function (DAD), behavior (NPI), global disability (CDR) and dependence (DS). Caregiver time cost was significantly associated with all clinical measures of illness severity with a 1-unit change in MMSE, DAD, NPI, CDR and DS associated with a 11.57%, 4.81-4.97%, 3.58-3.67%, 42.52% and 71.05% change, respectively, in primary caregiver time cost. The association between caregiver time cost and DS was the strongest of all the associations examined. Caregiver time costs increase with increasing AD severity in all key domains of AD (cognition, function, behavior, global disability and dependence on others). Our analysis demonstrated that patient dependence is a particularly important predictor of caregiver time costs and should be considered as a potential outcome measure in intervention clinical trials in AD. Pfizer Inc. and Janssen Alzheimer Immunotherapy Research and Development.

  5. Regional variation on the presentation of Alzheimer's disease patients in memory clinics within Europe: data from the ICTUS study.

    Science.gov (United States)

    Hausner, Lucrezia; Frölich, Lutz; Gardette, Virginie; Reynish, Emma; Ousset, Pierre-Jean; Andrieu, Sandrine; Vellas, Bruno; On Behalf Of The Ictus-Eadc Study Group

    2010-01-01

    This study set out to describe the variations within Europe for Alzheimer's disease (AD) patients with regards to clinical and socio-demographic features, co-morbidities, drug treatment, and psychosocial care. 1,379 mild to moderate AD subjects from the ICTUS study were clustered into four geographic regions according to WHO-classification of European countries. Northern patients showed the mildest severity of dementia (MMSE: 21.6 +/- 3.7, p< 0.001), received the lowest rate of concomitant psychotropic drug treatment (24.3%, p< 0.001), and appeared to be healthier than patients in the rest of Europe. Western subjects were diagnosed earliest (0.5 +/- 0.9 month, p< 0.001), received the highest rate of formal care (45.0%, p< 0.001), and had the highest rates of antidementia drug treatment (60.4%, p< 0.001). Southern subjects had the shortest education period (5.6 +/- 4.0, p< 0.001), the most severe cognitive decline in MMSE: 19.8 +/- 4.0, $p<$ 0.001 and ADAScog: 24.2 9.6, p< 0.001 and received less antidementia drug treatment (37.6%; p< 0.001), lived more often with their caregivers (74.4%, p< 0.001), and had the highest caregiver burden (22.6 +/- 15.2, p=0.049). Eastern AD subjects received more concomitant psychopharmacological drugs (68.6%, p< 0.001), caregivers were more often different (18.6%, p< 0.001) from spouse or offspring, caregiver burden was lowest (18.7 +/- 12.4, p=0.049), nearly all subjects received only informal care (95.7%, p< 0.001) and were affected more by co-morbidities. Overall, these data show differences in socio-demographic and clinical characteristics between AD patients from four European geographical regions. The presentation and management of AD in Europe appears to differ according to European regions and likely reflects differences in cultural factors and health politics.

  6. Clinical management and associated costs for moderate and severe Alzheimer's disease in urban China: a Delphi panel study.

    Science.gov (United States)

    Yu, Xin; Chen, Shengdi; Chen, Xiaochun; Jia, Jianjun; Li, Chunhou; Liu, Cong; Toumi, Mondher; Milea, Dominique

    2015-01-01

    Healthcare resource utilisation for Alzheimer's disease (AD) in China is not well understood. This Delphi panel study aimed to describe the clinical management pathways for moderate and severe AD patients in urban China and to define the amount and cost of healthcare resources used. A panel of 11 experts was recruited from urban China to participate in two rounds of preparatory interviews. In the first round, 9 physicians specialised in dementia gave a qualitative description of the clinical management of AD patients. In the second round, 2 hospital administrators were asked about the cost of AD management and care. Results from the interviews were discussed by the experts in a Delphi panel meeting, where consensus was reached on quantitative aspects of AD management, including the rate of healthcare resource utilisation, the respective unit costs and caregiving time. Interviewees reported that mild AD is under-recognised in China; most patients are diagnosed with moderate to severe AD. Loss of independence and agitation/aggression are the main drivers for healthcare resource utilisation and contribute to a heavier caregiver burden. It was estimated that 70 % moderate AD patients are independent/non-aggressive at the time of diagnosis, 15 % are independent/aggressive, 10 % are dependent/non-aggressive, and 5 % are dependent/aggressive. Dependent/aggressive AD patients are more likely to be hospitalised (70-90 %) than accepted in a nursing home (0-20 %), while the opposite is true for dependent/non-aggressive patients (5-35 % for hospitalisation vs. 80 % for nursing home). Independent AD patients require 1-3 hours/day of caregiver time, while dependent patients can require up to 12-15 hours/day. Experts agreed that AD complicates the management of age-related comorbidities, found in 70-80 % of all AD patients, increasing the frequency and cost of hospitalisation. The Delphi panel approach was an efficient method of gathering data about the amount of

  7. Weight loss and undernutrition in community-dwelling patients with Alzheimer's dementia From population based studies to clinical management

    NARCIS (Netherlands)

    Droogsma, E.; Asselt, D.; De Deyn, Peter

    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;

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

    Science.gov (United States)

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

    2012-01-01

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

  9. Alzheimer's Disease

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

    Endo, Riuko

    1989-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

    There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites. Copyright © 2015. Published by Elsevier B.V.

  12. Clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale change in relation to goal attainment in patients on cholinesterase inhibitors.

    Science.gov (United States)

    Rockwood, Kenneth; Howlett, Susan E; Hoffman, Deborah; Schindler, Rachel; Mitnitski, Arnold

    2017-10-01

    The clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) subscale change is disputed. We compared 2- to 4-point ADAS-Cog changes with changes in Goal Attainment Scaling (GAS) and everyday function across initial ADAS-Cog scores and treatment responses. This exploratory analysis evaluated mild-moderate Alzheimer's disease patients treated with donepezil (12 months) or galantamine (8 months). Clinical meaningfulness was defined as concomitant ADAS-Cog and GAS changes of ±3 points and/or functional improvement. Patients with ≥3-point ADAS-Cog improvement significantly improved on GAS but not on standard tests of everyday function. ADAS-Cog "no change" (≤±3 points) was seen with mean GAS improvement. Initial ADAS-Cog improvement made endpoint improvement (ADAS-Cog 3 points and GAS 1 point) more likely (odds ratio = 6.9; 95% confidence interval = 2.5-19.5). In contrast, initial deterioration made endpoint improvement unlikely (0.33; 0.14-0.64). ADAS-Cog improvement and no change were each associated with GAS improvement. Initial ADAS-Cog worsening was unlikely to result in later improvement. ISRCTN26167328. Copyright © 2017. Published by Elsevier Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

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

    International Nuclear Information System (INIS)

    Teipel, Stefan; Grothe, Michel J.

    2016-01-01

    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.)

  15. Alzheimer disease: An interactome of many diseases

    Directory of Open Access Journals (Sweden)

    Balaji S Rao

    2014-01-01

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

  16. Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial.

    Science.gov (United States)

    Schneider, Lon S; Frangakis, Constantine; Drye, Lea T; Devanand, D P; Marano, Christopher M; Mintzer, Jacob; Mulsant, Benoit H; Munro, Cynthia A; Newell, Jeffery A; Pawluczyk, Sonia; Pelton, Gregory; Pollock, Bruce G; Porsteinsson, Anton P; Rabins, Peter V; Rein, Lisa; Rosenberg, Paul B; Shade, David; Weintraub, Daniel; Yesavage, Jerome; Lyketsos, Constantine G

    2016-05-01

    Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed. In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each. Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam. Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.

  17. Amyloid beta peptide immunotherapy in Alzheimer disease.

    Science.gov (United States)

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

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Orestes V. Forlenza

    2010-09-01

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

  19. Clinical neuropathology practice news 3-2012: the "ABC" in AD-revised and updated guideline for the neuropathologic assessment of Alzheimer's disease.

    Science.gov (United States)

    Kovacs, Gabor G; Gelpi, Ellen

    2012-01-01

    The two major approaches for the neuropathological assessment of Alzheimer's disease (AD) related pathology have been based on the assessment of neuritic plaques (CERAD) and neurofibrillary pathology (Braak and Braak). In 1997 these two approaches were integrated in the criteria and recommendations of the National Institute on Aging and the Reagan Institute Working group. Recently a new guideline has been published by the National Institute on Aging-Alzheimer's Association. This new guideline recognizes the existence of a pre-clinical stage of AD as part of continuous neuropathological changes in the background of the disease process, and it fosters the assessment of amyloid-beta phases in addition to neurofibrillary degeneration and neuritic plaques following an "ABC" score. Further, it suggests protocols for the neuropathological assessment of additional/concomitant neurodegenerative and vascular pathologies. Altogether, the new guideline responds to the need for an update of the existing "1997 criteria" for AD. Continued studies will have to assess the added value of the new approach and the influence of interlaboratory and/or methodological differences on the implementation of these new recommendations.

  20. Impact of Alzheimer's Disease, Lewy Body and Vascular Co-Pathologies on Clinical Transition to Dementia in a National Autopsy Cohort.

    Science.gov (United States)

    Pillai, Jagan A; Butler, Robert S; Bonner-Jackson, Aaron; Leverenz, James B

    2016-01-01

    We examined the effect of vascular or Lewy body co-pathologies in subjects with autopsy-confirmed Alzheimer's disease (AD) on the rate of cognitive and functional decline and transition to dementia. In an autopsy sample of prospectively characterized subjects from the National Alzheimer's Coordinating Center database, neuropathology diagnosis was used to define the groups of pure AD (pAD, n = 84), mixed vascular and AD (ADV, n = 54), and mixed Lewy body disease and AD (ADLBD, n = 31). Subjects had an initial Clinical Dementia Rating-Global (CDR-G) score 1, ≥3 evaluations, and Braak tangle stage ≥III. We compared the rate of cognitive and functional decline between the groups. The rate of functional and cognitive decline was lower for ADV, and ADV patients had less severe deficits on CDR-G and the CDR-Sum of Boxes scores at the last visit than pAD and ADLBD patients. No significant differences were noted between ADLBD and pAD patients. After controlling for age at death, the odds of reaching CDR ≥1 at the last visit were lower in the ADV subjects compared to the pAD subjects. The mean rate of functional and cognitive decline among ADV subjects was slower than among either pAD or ADLBD patients. Vascular pathology did not increase the odds of attaining CDR ≥1 when occurring with AD in this national cohort. © 2016 S. Karger AG, Basel.

  1. Meeting report on the Alzheimer?s Drug Discovery Foundation 14th International Conference on Alzheimer?s Drug Discovery

    OpenAIRE

    Friedman, Lauren G; Price, Katherine; Lane, Rachel F; Carman, Aaron J; Dacks, Penny A; Shineman, Diana W; Fillit, Howard M

    2014-01-01

    The Alzheimer?s Drug Discovery Foundation?s 14th International Conference on Alzheimer?s Drug Discovery was held on 9 and 10 September in Jersey City, NJ, USA. This annual meeting highlights novel therapeutic approaches supported by the Alzheimer?s Drug Discovery Foundation in development for Alzheimer?s disease and related dementias.

  2. Quiz: Alzheimer's Disease

    Science.gov (United States)

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

  3. 99mTc-HMPAO-SPECT in the diagnosis of senile dementia of Alzheimer's type - a study under clinical routine conditions

    International Nuclear Information System (INIS)

    Stoppe, G.; Staedt, J.; Schuetze, R.; Kunert, H.J.; Ruether, E.; Koegler, A.; Sandrock, D.; Emrich, D.

    1995-01-01

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

  4. Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

    Science.gov (United States)

    Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

    1991-12-01

    One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

  5. Memantine for treatment of moderate or severe Alzheimer's disease patients in urban China: clinical and economic outcomes from a health economic model.

    Science.gov (United States)

    Hu, Shanlian; Yu, Xin; Chen, Shengdi; Clay, Emilie; Toumi, Mondher; Milea, Dominique

    2015-01-01

    To estimate the clinical and economic benefits of memantine treatment initiated in moderate Alzheimer's disease (AD) in China, compared with initiation in severe AD only. A Markov model with a 5-year time horizon simulated moderate patients' progression through health states. Two groups were compared: patients receiving memantine from the moderate stage (i.e., at model entry), continuing treatment when reaching the severe stage; patients initiating memantine only when they developed severe disease. After 5 years, fewer patients receiving memantine from the moderate stage were severe (49%), dependent (59%) or aggressive (47%) compared with moderate patients who initiated treatment from severe stage only (58, 67 and 55%, respectively). Total cost of care was lower for treatment from moderate stage (67 billion RMB) when compared with treatment from severe stage (73 billion RMB). In China, AD treatment with memantine from the moderate stage could result in substantial cost savings.

  6. CT study in Alzheimer's disease

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  7. Absence of Acanthocytosis in Huntington's Disease-like 2: A Prospective Comparison with Huntington's Disease

    Directory of Open Access Journals (Sweden)

    David G. Anderson

    2017-12-01

    Full Text Available Background: Huntington’s Disease-like 2 (HDL2 is classified as a neuroacanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington’s disease (HD.Methods: We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were prepared using international standards and reviewed by at least two blinded reviewers. An acanthocytosis rate of greater than 1.2% in the dry smear or greater than 3.7% in the wet smear was designated a priori as the threshold for clinical significance based on previously established standards. Flow cytometry was performed on all but four of the cases. Red cell membrane protein analysis was performed on all participants.Results: There were 12 HDL2, 13 HD, and 21 controls enrolled. None of the HD or HDL2 participants had defined acanthocytosis or other morphological abnormalities. None of the HD or HDL2 cases had evidence of an abnormal band 3.Discussion: Acanthocytosis was not identified in either HDL2 or HD in our patient population. Our results, based on the first prospective study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will not help establish the diagnosis of HD or HDL2, nor differentiate between the two disorders and raises the question if HDL2 should be placed within the neuroacanthocytosis syndromes.

  8. A Systematic Review of the Huntington Disease-Like 2 Phenotype.

    Science.gov (United States)

    Anderson, David G; Walker, Ruth H; Connor, Myles; Carr, Jonathan; Margolis, Russell L; Krause, Amanda

    2017-01-01

    Huntington Disease-like 2 (HDL2) is a neurodegenerative disorder similar to Huntington Disease (HD) in its clinical phenotype, genetic characteristics, neuropathology and longitudinal progression. Proposed specific differences include an exclusive African ancestry, lack of eye movement abnormalities, increased Parkinsonism, and acanthocytes in HDL2. The objective was to determine the similarities and differences between HD and HDL2 by establishing the clinical phenotype of HDL2 with the published cases. A literature review of all clinically described cases of HDL2 until the end of 2016 was performed and a descriptive analysis was carried out. Sixty-nine new cases were described between 2001 and 2016. All cases had likely African ancestry, and most were found in South Africa and the USA. Many features were found to be similar to HD, including a strong negative correlation between repeat length and age of onset. Chorea was noted in 48/57 cases (84%). Dementia was reported in 74% patients, and Parkinsonism in 37%. Psychiatric features were reported in 44 out of 47 cases. Patients with chorea had lower expanded repeat lengths compared to patients without chorea. Eye movements were described in 19 cases, 8 were abnormal. Acanthocytes were detected in 4 of the 13 patients tested. Nineteen out of 20 MRIs were reported as abnormal with findings similar to HD. This review clarifies some aspects of the HDL2 phenotype and highlights others which require further investigation. Features that are unique to HDL2 have been documented in a minority of subjects and require prospective validation.

  9. Harmonized diagnostic criteria for Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ames David

    2010-12-01

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

  11. Weight loss and undernutrition in community-dwelling patients with Alzheimer's dementia: From population based studies to clinical management.

    Science.gov (United States)

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

    2015-06-01

    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.

  12. Practical use of visual medial temporal lobe atrophy cut-off scores in Alzheimer's disease: Validation in a large memory clinic population

    Energy Technology Data Exchange (ETDEWEB)

    Claus, Jules J.; Holl, Dana C.; Roorda, Jelmen J. [Tergooi Hospital, Department of Neurology, Blaricum (Netherlands); Staekenborg, Salka S. [Tergooi Hospital, Department of Neurology, Blaricum (Netherlands); VU University Medical Center, Department of Neurology, Alzheimer Center, Amsterdam (Netherlands); Schuur, Jacqueline [Tergooi Hospital, Department of Geriatrics, Blaricum (Netherlands); Koster, Pieter [Tergooi Hospital, Department of Radiology, Blaricum (Netherlands); Tielkes, Caroline E.M. [Tergooi Hospital, Department of Medical Psychology, Blaricum (Netherlands); Scheltens, Philip [VU University Medical Center, Department of Neurology, Alzheimer Center, Amsterdam (Netherlands)

    2017-08-15

    To provide age-specific medial temporal lobe atrophy (MTA) cut-off scores for routine clinical practice as marker for Alzheimer's disease (AD). Patients with AD (n = 832, mean age 81.8 years) were compared with patients with subjective cognitive impairment (n = 333, mean age 71.8 years) in a large single-centre memory clinic. Mean of right and left MTA scores was determined with visual rating (Scheltens scale) using CT (0, no atrophy to 4, severe atrophy). Relationships between age and MTA scores were analysed with regression analysis. For various MTA cut-off scores, decade-specific sensitivity and specificity and area under the curve (AUC) values, computed with receiver operator characteristic curves, were determined. MTA strongly increased with age in both groups to a similar degree. Optimal MTA cut-off values for the age ranges <65, 65-74, 75-84 and ≥85 were: ≥1.0, ≥1.5, ≥ 2.0 and ≥2.0. Corresponding values of sensitivity and specificity were 83.3% and 86.4%; 73.7% and 84.6%; 73.7% and 76.2%; and 84.0% and 62.5%. From this large unique memory clinic cohort we suggest decade-specific MTA cut-off scores for clinical use. After age 85 years, however, the practical usefulness of the MTA cut-off is limited. (orig.)

  13. Practical use of visual medial temporal lobe atrophy cut-off scores in Alzheimer's disease: Validation in a large memory clinic population

    International Nuclear Information System (INIS)

    Claus, Jules J.; Holl, Dana C.; Roorda, Jelmen J.; Staekenborg, Salka S.; Schuur, Jacqueline; Koster, Pieter; Tielkes, Caroline E.M.; Scheltens, Philip

    2017-01-01

    To provide age-specific medial temporal lobe atrophy (MTA) cut-off scores for routine clinical practice as marker for Alzheimer's disease (AD). Patients with AD (n = 832, mean age 81.8 years) were compared with patients with subjective cognitive impairment (n = 333, mean age 71.8 years) in a large single-centre memory clinic. Mean of right and left MTA scores was determined with visual rating (Scheltens scale) using CT (0, no atrophy to 4, severe atrophy). Relationships between age and MTA scores were analysed with regression analysis. For various MTA cut-off scores, decade-specific sensitivity and specificity and area under the curve (AUC) values, computed with receiver operator characteristic curves, were determined. MTA strongly increased with age in both groups to a similar degree. Optimal MTA cut-off values for the age ranges <65, 65-74, 75-84 and ≥85 were: ≥1.0, ≥1.5, ≥ 2.0 and ≥2.0. Corresponding values of sensitivity and specificity were 83.3% and 86.4%; 73.7% and 84.6%; 73.7% and 76.2%; and 84.0% and 62.5%. From this large unique memory clinic cohort we suggest decade-specific MTA cut-off scores for clinical use. After age 85 years, however, the practical usefulness of the MTA cut-off is limited. (orig.)

  14. The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial

    Directory of Open Access Journals (Sweden)

    Gorman Mary

    2007-08-01

    Full Text Available Abstract Background In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness. Methods This is a secondary analysis of a 12 month open-label study of 100 patients (71 women diagnosed with mild to moderate AD treated with 5–10 mg of donepezil daily. We studied the observed case, 6-month change from baseline on the ADAS-Cog, the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus, patient-Goal Attainment Scaling (PGAS and clinician-GAS (CGAS. Results At 6 months, donepezil-treated patients (n = 95 were more likely to show no change (+/- 3 points on the ADAS-Cog (56% than to improve (20% or decline (24% by 4-points. ADAS-Cog change scores were little correlated with other measures: from -0.09 for PGAS to 0.27 for the CIBIC-Plus. While patients who improved on the ADAS-Cog were less likely to decline on the clinical measures (26%, 43% of patients who declined on the ADAS-Cog improved on at least two of the clinical measures. Conclusion The ADAS-Cog did not capture all clinically important effects. In general, ADAS-Cog improvement indicates clinical improvement, whereas many people with ADAS-Cog decline do not show clinical decline. The open-label design of this study does not allow us to know whether this is a treatment effect, which requires further investigation.

  15. The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial.

    Science.gov (United States)

    Rockwood, Kenneth; Fay, Sherri; Gorman, Mary; Carver, Daniel; Graham, Janice E

    2007-08-30

    In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness. This is a secondary analysis of a 12 month open-label study of 100 patients (71 women) diagnosed with mild to moderate AD treated with 5-10 mg of donepezil daily. We studied the observed case, 6-month change from baseline on the ADAS-Cog, the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-Plus), patient-Goal Attainment Scaling (PGAS) and clinician-GAS (CGAS). At 6 months, donepezil-treated patients (n = 95) were more likely to show no change (+/- 3 points) on the ADAS-Cog (56%) than to improve (20%) or decline (24%) by 4-points. ADAS-Cog change scores were little correlated with other measures: from -0.09 for PGAS to 0.27 for the CIBIC-Plus. While patients who improved on the ADAS-Cog were less likely to decline on the clinical measures (26%), 43% of patients who declined on the ADAS-Cog improved on at least two of the clinical measures. The ADAS-Cog did not capture all clinically important effects. In general, ADAS-Cog improvement indicates clinical improvement, whereas many people with ADAS-Cog decline do not show clinical decline. The open-label design of this study does not allow us to know whether this is a treatment effect, which requires further investigation.

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

    DEFF Research Database (Denmark)

    Soininen, Hilkka; Mattila, Jussi; Koikkalainen, Juha

    2012-01-01

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

  17. Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease.

    Science.gov (United States)

    Choe, Young Min; Kim, Ki Woong; Jhoo, Jin Hyeong; Ryu, Seung Ho; Seo, Eun Hyun; Sohn, Bo Kyung; Byun, Min Soo; Bak, Jae-Hwa; Lee, Jong-Min; Yun, Hyuk Jin; Han, Myeong-Il; Woo, Jong Inn; Lee, Dong Young

    2016-07-01

    A series of preclinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects. The present study primarily aimed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer's disease (AD). We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants. Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and randomly assigned in a 1:1 ratio. Each group received 20 mg/day of escitalopram or placebo for 52 weeks. The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks. The Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia (CSDD) were also applied. We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups. Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo (t = -2.17, df = 50.42, p = 0.035), but this finding did not persist throughout the study. The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD. However, the negative results of the present trial should be interpreted cautiously because of the relatively small sample size. Further large-scale escitalopram trials targeting the earlier stages of AD, even prodromal AD, are still needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. The clinical efficacy of reminiscence therapy in patients with mild-to-moderate Alzheimer disease: Study protocol for a randomized parallel-design controlled trial.

    Science.gov (United States)

    Li, Mo; Lyu, Ji-Hui; Zhang, Yi; Gao, Mao-Long; Li, Wen-Jie; Ma, Xin

    2017-12-01

    Alzheimer disease (AD) is one of the most common diseases among the older adults. Currently, various nonpharmacological interventions are used for the treatment of AD. Such as reminiscence therapy is being widely used in Western countries. However, it is often used as an empirical application in China; the evidence-based efficacy of reminiscence therapy in AD patients remains to be determined. Therefore, the aim of this research is to assess the effectives of reminiscence therapy for Chinese elderly. This is a randomized parallel-design controlled trial. Mild and moderate AD patients who are in the Beijing Geriatric Hospital, China will be randomized into control and intervention groups (n = 45 for each group). For the intervention group, along with conventional drug therapy, participants will be exposed to a reminiscence therapy of 35 to 45 minutes, 2 times/wk for 12 consecutive weeks. Patients in the control group will undergo conventional drug therapy only. The primary outcome measure will be the differences in Alzheimer disease Assessment Scale-Cognitive Section Score. The secondary outcome measures will be the differences in the Cornell scale for depression in dementia, Neuropsychiatric Inventory score, and Barthel Index scores at baseline, at 4 and 12 weeks of treatment, and 12 weeks after treatment. The protocols have been approved by the ethics committee of Beijing Geriatric Hospital of China (approval no. 2015-010). Findings will be disseminated through presentation at scientific conferences and in academic journals. Chinese Clinical Trial Registry identifier ChiCTR-INR-16009505. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Abhijit N. Gurav

    2014-01-01

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

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

    Science.gov (United States)

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

    2009-02-01

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

  1. Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer's disease.

    Science.gov (United States)

    Papp, Kathryn V; Amariglio, Rebecca E; Mormino, Elizabeth C; Hedden, Trey; Dekhytar, Maria; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

    2015-07-01

    Furthering our understanding of the relationship between amyloidosis (Aβ), neurodegeneration (ND), and cognition is imperative for early identification and early intervention of Alzheimer's disease (AD). However, the subtle cognitive decline differentially associated with each biomarker-defined stage of preclinical AD has yet to be fully characterized. Recent work indicates that different components of memory performance (free and cued recall) may be differentially specific to memory decline in prodromal AD. We sought to examine the relationship between free and cued recall paradigms, in addition to global composites of memory, executive functioning, and processing speed in relation to stages of preclinical AD. A total of 260 clinically normal (CN) older adults (CDR=0) from the Harvard Aging Brain study were grouped according to preclinical AD stages including Stage 0 (Aβ-/ND-), Stage 1 (Aβ+/ND-), Stage 2 (Aβ+/ND+), and suspected non-Alzheimer's associated pathology (SNAP; Aβ-/ND+). General linear models controlling for age, sex, and education were used to assess for stage-based performance differences on cognitive composites of executive functioning, processing speed, and memory in addition to free and cued delayed recall on the Selective Reminding Test (SRT) and Memory Capacity Test (MCT). Global memory performance differed between preclinical stages with Stage 2 performing worse compared with Stage 0. When examining free and cued paradigms by memory test, only the MCT (and not the SRT) revealed group differences. More specifically, Stage 1 was associated with decrements in free recall compared with Stage 0 while Stage 2 was associated with decrements in both free and cued recall. There was a trend for the SNAP group to perform worse on free recall compared with Stage 0. Finally, there was no association between preclinical stage and global composites of executive functioning or processing speed. Clinically normal older adults with underlying evidence of

  2. Alzheimer's Disease Information Page

    Science.gov (United States)

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

  3. Enfermedad de Alzheimer

    OpenAIRE

    Serrano Reyes, Carlos Daniel; Fundación Valle de Lili

    2001-01-01

    ¿Cuáles son las manifestaciones de la enfermedad de Alzheimer?/ Signos de alarma de la enfermedad de Alzheimer/ ¿Cómo se diagnostica la enfermedad?/ ¿Cómo se trata la enfermedad de Alzheimer?/ ¿Qué se está investigando sobre la enfermedad?/ ¿Qué otras enfermedades se parecen al Alzheimer?

  4. 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.

    2016-01-01

    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

  5. Long-term changes in ADAS-cog: what is clinically relevant for disease modifying trials in Alzheimer?

    Science.gov (United States)

    Vellas, B; Andrieu, S; Cantet, C; Dartigues, J F; Gauthier, S

    2007-01-01

    With the development of long-term disease modifying trials, changes in ADAS-Cog at 18 months will rise certainly many questions. We decided to look in the Real.fr study at the links between changes in cognition, ADAS-Cog and function. A total of 346 Alzheimer's patients with ADAS-cog at entry and at 18 months. were eligible for this analysis. These patients were on average 77.44 years old and 254 (72.36%) were women. The great majority lived at home and about 93% were treated with a cholinesterase inhibitor at baseline. Thirty three patients (9%) had a gain of more than 2 points at the ADAS-cog at 18 months (Group I, improvement); 130 (38%) were considered as stable, the reference group (Group II ) characterized by a stability at the ADAS-cog: decline of 2 points to gain of 2 points, 112 subjects (32%) had a moderate decline between 2 and 7 at the ADAScog (Group III) and finally 71 subjects (21%) had a severe impairment more than seven points at the ADAS-cog. A loss of one Basic ADL is certainly highly relevant, and such a change was found at 18 months in more than half of the subjects, which is not surprising for a long-term evolution in mild to moderate AD. An impairment of more than 7 points at the ADAS-cog was found in 21% of the subjects at 18 months and was associated with loss.

  6. Clinical use of regional Tc-99m-HMPAO uptake in dementia of the Alzheimer type (DAT)

    International Nuclear Information System (INIS)

    Gebhardt, U.; Schmauss, F.; Wagner-Manslau, C.; Buttermann, G.; Zimmer, R.

    1993-01-01

    In 46 patients with dementia of the Alzheimer type (DAT) regional cerebral blood flow (rCBF) was compared with cognitive performance (MMSE, CAMCOG). The cortico-cerebellar ratio (CCR), determined by 99m Tc-HMPAO-SPECT was used as a rCBF-equivalent. In the mild demented group we found a bilateral CCR-reduction parietal posterior, in moderate DAT bilateral temporoparietal and leftsided frontolateral defects were seen. Severe DAT showed an additional perfusion decrease mid frontal. With increasing severity of DAT an asymmetric perfusion occurred in 17/46 patients with accentuated CCR-reduction on the left side (temporal>parietal). High correlations between CCR and MMSE (r≥0.70) existed frontolateral, temporal and parietal in the left hemisphere. Significant associations between CCR and CAMCOG were obtained for language in the left temporal posterior region (r=0.64), for memory task left temporal anterior (r=0.59) and for praxis left parietal posterior (r=0.55). In detecting rCBF abnormalities the sensitivity for all 46 DAT patients was 91% and 70% in the mild cases. (orig.) [de

  7. Impact of (18)FDG PET and (11)C-PIB PET brain imaging on the diagnosis of Alzheimer's disease and other dementias in a regional memory clinic in Hong Kong.

    Science.gov (United States)

    Shea, Y F; Ha, J; Lee, S C; Chu, L W

    2016-08-01

    This study investigated the improvement in the accuracy of diagnosis of dementia subtypes among Chinese dementia patients who underwent [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) with or without carbon 11-labelled Pittsburgh compound B ((11)C-PIB). This case series was performed in the Memory Clinic at Queen Mary Hospital, Hong Kong. We reviewed 109 subjects (56.9% were female) who received PET with or without (11)C-PIB between January 2007 and December 2014. Data including age, sex, education level, Mini-Mental State Examination score, Clinical Dementia Rating scale score, neuroimaging report, and pre-/post-imaging clinical diagnoses were collected from medical records. The agreement between the initial and post-PET with or without (11)C-PIB dementia diagnosis was analysed by the Cohen's kappa statistics. The overall accuracy of initial clinical diagnosis of dementia subtype was 63.7%, and diagnosis was subsequently changed in 36.3% of subjects following PET with or without (11)C-PIB. The rate of accurate initial clinical diagnosis (compared with the final post-imaging diagnosis) was 81.5%, 44.4%, 14.3%, 28.6%, 55.6% and 0% for Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, other dementia, and mixed dementia, respectively. The agreement between the initial and final post-imaging dementia subtype diagnosis was only fair, with a Cohen's kappa of 0.25 (95% confidence interval, 0.05-0.45). For the 21 subjects who underwent (11)C-PIB PET imaging, 19% (n=4) of those with Alzheimer's disease (PIB positive) were initially diagnosed with non-Alzheimer's disease dementia. In this study, PET with or without (11)C-PIB brain imaging helped improve the accuracy of diagnosis of dementia subtype in 36% of our patients with underlying Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

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

    Science.gov (United States)

    Reddy, P Hemachandra

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.

    Science.gov (United States)

    Atri, Alireza; Frölich, Lutz; Ballard, Clive; Tariot, Pierre N; Molinuevo, José Luis; Boneva, Neli; Windfeld, Kristian; Raket, Lars L; Cummings, Jeffrey L

    2018-01-09

    New therapeutic approaches for Alzheimer disease (AD) are needed. To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  12. Nutritional supplementation for Alzheimer's disease?

    Science.gov (United States)

    Shea, Thomas B; Remington, Ruth

    2015-03-01

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

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

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

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

    Directory of Open Access Journals (Sweden)

    Luciana Pricoli Vilela

    2006-06-01

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

  15. A Clinically-Translatable Machine Learning Algorithm for the Prediction of Alzheimer's Disease Conversion in Individuals with Mild and Premild Cognitive Impairment.

    Science.gov (United States)

    Grassi, Massimiliano; Perna, Giampaolo; Caldirola, Daniela; Schruers, Koen; Duara, Ranjan; Loewenstein, David A

    2018-01-01

    Available therapies for Alzheimer's disease (AD) can only alleviate and delay the advance of symptoms, with the greatest impact eventually achieved when provided at an early stage. Thus, early identification of which subjects at high risk, e.g., with MCI, will later develop AD is of key importance. Currently available machine learning algorithms achieve only limited predictive accuracy or they are based on expensive and hard-to-collect information. The current study aims to develop an algorithm for a 3-year prediction of conversion to AD in MCI and PreMCI subjects based only on non-invasively and effectively collectable predictors. A dataset of 123 MCI/PreMCI subjects was used to train different machine learning techniques. Baseline information regarding sociodemographic characteristics, clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy was used to extract 36 predictors. Leave-pair-out-cross-validation was employed as validation strategy and a recursive feature elimination procedure was applied to identify a relevant subset of predictors. 16 predictors were selected from all domains excluding sociodemographic information. The best model resulted a support vector machine with radial-basis function kernel (whole sample: AUC = 0.962, best balanced accuracy = 0.913; MCI sub-group alone: AUC = 0.914, best balanced accuracy = 0.874). Our algorithm shows very high cross-validated performances that outperform the vast majority of the currently available algorithms, and all those which use only non-invasive and effectively assessable predictors. Further testing and optimization in independent samples will warrant its application in both clinical practice and clinical trials.

  16. Profile of the Paraoxonase 1 (PON1 Gene 192Q/R Polymorphism and Clinical Associations among Older Singaporean Chinese with Alzheimer's and Mixed Dementia

    Directory of Open Access Journals (Sweden)

    Dennis C.C. Seow

    2016-02-01

    Full Text Available Background: To examine the prevalence of the Paraoxonase1 (PON1 gene 192Q/R polymorphism amongst Singaporean Chinese with Alzheimer's disease (AD and mixed dementia and possible clinical associations. Methods: We examined the presence of the PON1 192Q/R polymorphism together with cognitive status, functional status and neuropsychiatric symptoms among 186 older Singaporean Chinese with AD (n = 109 and mixed dementia (n = 77. Results: The R allele predominated in 67% of the AD patients and 63.1% of the patients with mixed dementia. Within the mixed dementia subgroup, the R allele was significantly associated with a higher BADLS score, NPI-Q scores and CDR scores. Conclusion: Among older Singaporean Chinese with AD and mixed dementia, the R allele was predominant. In particular, within the mixed dementia subgroup, the R allele carrier status was associated with poorer functional status, greater presence of neuropsychiatric symptoms and a more severe stage of dementia. Further studies should be conducted.

  17. Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Clinical Evidence and Possible Mechanisms

    Science.gov (United States)

    Scuteri, Damiana; Morrone, Luigi Antonio; Rombolà, Laura; Avato, Pina Rosa; Corasaniti, Maria Tiziana; Sakurada, Shinobu; Sakurada, Tsukasa

    2017-01-01

    The treatment of agitation and aggression, typical Behavioural and Psychological Symptoms of Dementia (BPSDs) of Alzheimer's Disease (AD), is one of the most complicated aspects of handling patients suffering from dementia. Currently, the management of these symptoms often associated with an increased pain perception, which notably reduces the patients' quality of life (QoL), relies on the employment of antipsychotic drugs. Unfortunately, the use of these pharmacological agents has some limits: in the long term, they do not result in being equally effective as in the first weeks of treatment and they present important side effects. Therefore, there is growing interest, supported by clinical evidence, in aromatherapy for the control of agitation, aggression, and psychotic symptoms. Some molecular mechanisms have been proposed to explain the behavioural effects of essential oils, as the whole phytocomplex or the single components, but important basic research effort is still needed. For this reason, rigorous preclinical studies are necessary in order to understand the pharmacological basis of aromatherapy in the treatment of BPSDs and to widen the cluster of effective essential oils in pharmacotherapeutic practice. PMID:28465709

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

    Directory of Open Access Journals (Sweden)

    Marwan Sabbagh

    2016-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

    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). 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 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. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Shinohara, Masao; Kawakatsu, Shinobu; Morinobu, Shigeru; Oiji, Arata; Sagawa, Katsuo; Yazaki, Mitsuyasu; Totsuka, Shirou; Komatani, Akio; Yamaguchi, Koichi

    1989-01-01

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

  2. General practitioner's clinical practices, difficulties and educational needs to manage Alzheimer's disease in France: analysis of national telephone-inquiry data.

    Science.gov (United States)

    Somme, Dominique; Gautier, Arnaud; Pin, Stéphanie; Corvol, Aline

    2013-06-13

    The literature has emphasized the role of general practitioners (GPs) in caring for Alzheimer's disease (AD) patients. Within the framework of the French national AD plan, an inquiry was undertaken to identify the clinical practices, difficulties and training needs of GPs managing this pathology. A random sample from a representative national listing of continental French GPs following ≥1 AD patients comprised the study population. Participants completed a standard questionnaire on their clinical practices, difficulties and educational needs for AD management. Feeling insufficiently trained was subjected to univariate and multivariate analyses. A minority of the 974 respondents declared using questionnaires in their diagnostic evaluation (15.2%), told the patient the diagnosis (8.2%) and was aware of the national recommendations for AD (41.9%). Behavioral disorders represented the most common (73.5%) problem encountered, while half of the GPs considered management of comorbidities easy roles to fulfill. In comparison, coordination of care and assistance did not seem to be a primary problem. A score was calculated, attributing 1 point to each of the following items: need for further education in terms of communications with the family, with patients, disclosing the diagnosis, and non-drug treatments. The factors linked to feeling insufficiently trained for 3 or 4 of the 4 items were: female sex; not involved in educational programs (for parents/family and patients) and no activity related to training medical students. Our study identified gaps in French GP training concerning AD diagnosis practices and diagnosis announcement. GPs seemed aware of their educational needs and described difficulties in managing behavioral disorders. Our findings enabled the definition of policy priorities to provide training and disseminate information.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-08-01

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

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

    International Nuclear Information System (INIS)

    Waldman, A.D.; Rai, G.S.

    2003-01-01

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

  5. Comparison between clinical diagnosis and CSF biomarkers of Alzheimer disease in elderly patients with late onset psychosis: Helsinki Old Age Psychosis Study (HOPS).

    Science.gov (United States)

    Seppälä, Toni T; Louhija, Ulla-Marja; Appelberg, Björn; Herukka, Sanna-Kaisa; Juva, Kati

    2014-09-01

    To determine the proportion of elderly people with a first psychotic episode actually suffering from dementia, especially Alzheimer disease (AD), by using cerebrospinal fluid (CSF) biomarkers. Prospective case-control study. Sixty-six patients age 65 years and older with recent psychotic symptoms and 12 comparison subjects with chronic schizophrenia over 10 years that were referred to acute old age psychiatry, in-ward treatment. Concentration levels of CSF Aβ42, tau and p-tau-181 measured by ELISA compared to clinical diagnosis made by a multiprofessional team of one neurologist and several psychiatrists. The CSF specimen was obtained from 51 (65.4%) of the patients. In five subjects out of 13 with a clinical diagnosis of AD, all the CSF biomarkers (Aβ42, tau and p-tau) were normal. Only one patient out of 25 with a psychiatric diagnosis and none out of the comparison group with schizophrenia showed a CSF profile typical of AD. Three patients with an AD diagnosis, four patients with a psychiatric diagnosis and one patient with schizophrenia had a low Aβ42 concentration with normal levels of tau or p-tau. The patients with AD had lower CSF Aβ42 levels than other patients. The CSF biomarkers are important and useful as part of the diagnostic procedure for detecting AD and other dementia in elderly patients displaying psychotic symptoms. The accuracy of AD diagnosis encounters problems due to atypical behavioural symptoms in psychiatric settings and thus the differential diagnostics can be improved by using CSF biomarkers of AD more frequently. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yat-Fung Shea

    2016-02-01

    Full Text Available There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1 mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p < 0.001 and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively. Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03. Patients with amyloid precursor protein (APP mutations presented more frequently with aggression (p = 0.02 and those with APP duplication presented more frequently with apraxia (p = 0.03. PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001. Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02 and personality change (p = 0.01 but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02. Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites.

  7. The Alzheimer's Project

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here...... a successful example of this type of collaboration in the field of dementia....

  9. Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data.

    Science.gov (United States)

    Kocis, Petr; Tolar, Martin; Yu, Jeremy; Sinko, William; Ray, Soumya; Blennow, Kaj; Fillit, Howard; Hey, John A

    2017-06-01

    Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease. Therefore, to build on this important efficacy attribute and to further improve its pharmaceutical properties, we have developed a prodrug of tramiprosate ALZ-801 that is in advanced stages of clinical development. To elucidate how tramiprosate works, we investigated its molecular mechanism of action (MOA) and the translation to observed clinical outcomes. The two main objectives of this research were to (1) elucidate and characterize the MOA of tramiprosate via an integrated application of three independent molecular methodologies and (2) present an integrated translational analysis that links the MOA, conformation of the target, stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome in APOE4/4 homozygote subjects. We used three molecular analytical methods-ion mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR), and molecular dynamics-to characterize the concentration-related interactions of tramiprosate versus Aβ42 monomers and the resultant conformational alterations affecting aggregation into oligomers. The molecular stoichiometry of the tramiprosate versus Aβ42 interaction was further analyzed in the context of clinical pharmacokinetic dose exposure and central nervous system Aβ42 levels (i.e., pharmacokinetic-pharmacodynamic translation in humans). We observed a multi-ligand interaction of tramiprosate with monomeric Aβ42

  10. [Alzheimer's disease and olfaction].

    Science.gov (United States)

    Naudin, Marine; Mondon, Karl; Atanasova, Boriana

    2013-09-01

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

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

    Science.gov (United States)

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

    2014-06-01

    Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials. © 2014 John Wiley & Sons Ltd.

  12. The Structured Interview & Scoring Tool-Massachusetts Alzheimer's Disease Research Center (SIST-M): development, reliability, and cross-sectional validation of a brief structured clinical dementia rating interview.

    Science.gov (United States)

    Okereke, Olivia I; Copeland, Maura; Hyman, Bradley T; Wanggaard, Taylor; Albert, Marilyn S; Blacker, Deborah

    2011-03-01

    The Clinical Dementia Rating (CDR) and CDR Sum-of-Boxes can be used to grade mild but clinically important cognitive symptoms of Alzheimer disease. However, sensitive clinical interview formats are lengthy. To develop a brief instrument for obtaining CDR scores and to assess its reliability and cross-sectional validity. Using legacy data from expanded interviews conducted among 347 community-dwelling older adults in a longitudinal study, we identified 60 questions (from a possible 131) about cognitive functioning in daily life using clinical judgment, inter-item correlations, and principal components analysis. Items were selected in 1 cohort (n=147), and a computer algorithm for generating CDR scores was developed in this same cohort and re-run in a replication cohort (n=200) to evaluate how well the 60 items retained information from the original 131 items. Short interviews based on the 60 items were then administered to 50 consecutively recruited older individuals, with no symptoms or mild cognitive symptoms, at an Alzheimer's Disease Research Center. Clinical Dementia Rating scores based on short interviews were compared with those from independent long interviews. In the replication cohort, agreement between short and long CDR interviews ranged from κ=0.65 to 0.79, with κ=0.76 for Memory, κ=0.77 for global CDR, and intraclass correlation coefficient for CDR Sum-of-Boxes=0.89. In the cross-sectional validation, short interview scores were slightly lower than those from long interviews, but good agreement was observed for global CDR and Memory (κ≥0.70) as well as for CDR Sum-of-Boxes (intraclass correlation coefficient=0.73). The Structured Interview & Scoring Tool-Massachusetts Alzheimer's Disease Research Center is a brief, reliable, and sensitive instrument for obtaining CDR scores in persons with symptoms along the spectrum of mild cognitive change.

  13. Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications.

    Science.gov (United States)

    Pasinetti, Giulio Maria

    2012-10-01

    Recent studies suggest that by the middle of this century, as many as 14 million Americans will have Alzheimer's disease, creating an enormous strain on families, the health care system and the federal budget. There are still widespread misconceptions about issues related to the prevention and/or treatment of disease pathogenesis, leaving us unprepared to deal with the disease. To address these challenges, several therapeutic approaches are currently under investigation, mainly in an attempt to delay disease onset and eventually slow down its progression. Recent epidemiological evidence has implicated the protective role of dietary polyphenols from grape products against Alzheimer's disease. Furthermore, experimental evidence supports the hypothesis that certain bioactive grape-derived polyphenols may protect against Alzheimer's disease-type cognitive deterioration, in part by interfering with the generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species. Brain-targeting polyphenols have been shown to significantly reduce the generation of β-amyloid peptides in primary cortico-hippocampal neuron cultures, and preliminary results indicate that they may influence neuronal synaptic plasticity. Recent evidence has also implicated the role of certain grape-derived preparations in beneficially modulating tau neuropathology, including reducing tau aggregation. Studies suggest that dietary polyphenolics may benefit Alzheimer's disease by modulating multiple disease-modifying modalities, both β-amyloid-dependent and independent mechanisms, and provide impetus for the development of polyphenolic compounds for Alzheimer's disease prevention and/or therapy. Georg Thieme Verlag KG Stuttgart · New York.

  14. The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China.

    Science.gov (United States)

    Liu, Shuling; Jin, Yi; Shi, Zhihong; Huo, Ya Ruth; Guan, Yalin; Liu, Mengyuan; Liu, Shuai; Ji, Yong

    2017-06-01

    Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.

  15. Resource utilisation, costs and clinical outcomes in non-institutionalised patients with Alzheimer's disease: 18-month UK results from the GERAS observational study.

    Science.gov (United States)

    Lenox-Smith, Alan; Reed, Catherine; Lebrec, Jeremie; Belger, Mark; Jones, Roy W

    2016-11-25

    Alzheimer's disease (AD), the commonest cause of dementia, represents a significant cost to UK society. This analysis describes resource utilisation, costs and clinical outcomes in non-institutionalised patients with AD in the UK. The GERAS prospective observational study assessed societal costs associated with AD for patients and caregivers over 18 months, stratified according to baseline disease severity (mild, moderate, or moderately severe/severe [MS/S]). All patients enrolled had an informal caregiver willing to participate in the study. Healthcare resource utilisation was measured using the Resource Utilization in Dementia instrument, and 18-month costs estimated by applying unit costs of services and products (2010 values). Total societal costs were calculated using an opportunity cost approach. Overall, 526 patients (200 mild, 180 moderate and 146 MS/S at baseline) were recruited from 24 UK centres. Mini-Mental State Examination (MMSE) scores deteriorated most markedly in the MS/S patient group, with declines of 3.6 points in the mild group, 3.5 points in the moderate group and 4.7 points in the MS/S group; between-group differences did not reach statistical significance. Patients with MS/S AD dementia at baseline were more likely to be institutionalised (Kaplan-Meier probability 28% versus 9% in patients with mild AD dementia; p caregiver time and mean total societal costs. Total societal costs of £43,560 over 18 months were estimated for the MS/S group, versus £25,865 for the mild group and £30,905 for the moderate group (p informal caregiver costs at each AD dementia severity level. This study demonstrated a mean deterioration in MMSE score over 18 months in patients with AD. It also showed that AD is a costly disease, with costs increasing with disease severity, even when managed in the community: informal caregiver costs represented the main contributor to societal costs.

  16. [Profile of the informal carer associated with the clinical management of the Alzheimer's disease patient refractory to symptomatic treatment of the disease].

    Science.gov (United States)

    Molinuevo, J L; Hernández, B

    2011-11-01

    Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as, time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers' quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (pCaregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p=.021). Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  17. Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease.

    Science.gov (United States)

    Persson, Karin; Barca, Maria Lage; Eldholm, Rannveig Sakshaug; Cavallin, Lena; Šaltytė Benth, Jūratė; Selbæk, Geir; Brækhus, Anne; Saltvedt, Ingvild; Engedal, Knut

    2017-01-01

    To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE ɛ4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (p = 0.075), where delayed recall and APOE ɛ4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. In adjusted models, memory function, APOE ɛ4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia. © 2017 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2009-01-01

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

  19. Visual hallucinations in Alzheimer's disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies.

    Directory of Open Access Journals (Sweden)

    Pai-Yi Chiu

    Full Text Available Visual hallucinations (VHs are among the most striking features of dementia with Lewy bodies (DLB. Given that Lewy body pathology is frequently observed in the brains of patients with AD, we aimed to study factors associated with VHs in AD and examine their association with DLB features. This cross-sectional study enrolled a consecutive series of AD patients who visited the dementia clinic of a regional hospital. Clinically diagnosed possible or probable DLB cases were excluded. VH frequency and associated factors including age, sex, education, disease severity, DLB features, vascular risk factors, cognitive function, and neuropsychiatric symptoms were compared between AD patients with VHs (VH+ and those without VHs (VH-. Among a total of 295 patients analyzed, 42 (14.2% had VHs. After adjusting for age, sex, and disease severity, DLB features including fluctuations in cognition scores, rapid-eye-movement behavioral disorder (RBD, and severe neuroleptic sensitivity were more frequent in the VH+ group. Furthermore, depression score, total Neuropsychiatric Inventory (NPI score, and total caregiver burden score as assessed by the NPI were higher in the VH+ group. Among neuropsychiatric symptoms, delusions, hallucinations in the non-visual domains, anxiety, and disinhibition were more frequent in the VH+ group. Conversely, none of the vascular risk factors (VRFs or cognitive domains of the Cognitive Abilities Screening Instrument (CASI was associated with VHs in AD. In summary, VHs, albeit occurring at a low rate, had a high impact on AD. Diagnostic features of DLB, including fluctuations, RBD, and severe neuroleptic sensitivity were significantly associated with VHs in AD. AD patients with VHs tended to have more severe neuropsychiatric symptoms and greater caregiver burden.

  20. Synaptic changes in Alzheimer's disease in vivo

    International Nuclear Information System (INIS)

    Mueller-Gaertner, H.W.

    1994-01-01

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

  1. Active Vaccines for Alzheimer Disease Treatment.

    Science.gov (United States)

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

    2016-09-01

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

  2. Galantamine for Alzheimer's disease.

    Science.gov (United States)

    Olin, J; Schneider, L

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  6. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  7. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  8. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  9. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  10. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  11. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  13. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  14. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  15. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

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

  16. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  17. Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3 gene; first reported case from Botswana.

    Science.gov (United States)

    Ocampo, C; Daimari, R; Oyekunle, A A

    2018-01-01

    Huntington's disease-like 2 (HDL2) is a rare autosomal dominant progressive neurodegenerative disorder commonly seen in adults. It was first described in a large African-American family in the United States. HDL2 clinically resembles Huntington's disease (HD) and causes adult-onset relentlessly progressive movement, emotional and cognitive dysfunction. Onset is usually in the fourth decade with slow progression to death. We present a 47-year-old male Botswana native, with a four-year-history of chorea, slurred speech, mood instability, cognitive impairment and weight loss. Genetic testing reveals normal HTT gene but a heterozygous expansion mutation at the JPH3 locus, confirmatory of HDL2. Though some cases of HDL2 have been reported from neighboring South Africa, this is the first instance from Botswana. This report draws attention to the fact that HDL2 exists among native Batswana, and even though clinically indistinguishable from HD, molecular testing can result in positive case identification. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-04-01

    Detecting at-risk individuals within a healthy population is critical for preventing or delaying Alzheimer's disease. Systems biology integration of brain and body metabolism enables peripheral metabolic biomarkers to serve as reporters of brain bioenergetic status. Using clinical metabolic data derived from healthy postmenopausal women in the Early versus Late Intervention Trial with Estradiol (ELITE), we conducted principal components and k-means clustering analyses of 9 biomarkers to define metabolic phenotypes. Metabolic clusters were correlated with cognitive performance and analyzed for change over 5 years. Metabolic biomarkers at baseline generated 3 clusters, representing women with healthy, high blood pressure, and poor metabolic phenotypes. Compared with healthy women, poor metabolic women had significantly lower executive, global and memory cognitive performance. Hormone therapy provided metabolic benefit to women in high blood pressure and poor metabolic phenotypes. This panel of well-established clinical peripheral biomarkers represents an initial step toward developing an affordable, rapidly deployable, and clinically relevant strategy to detect an at-risk phenotype of late-onset Alzheimer's disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Eye Movements in Alzheimer?s Disease

    OpenAIRE

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

    2015-01-01

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

  20. Evaluating the efficacy of a web-based program (diapason) for informal caregivers of patients with Alzheimer's disease: protocol for a randomized clinical trial.

    Science.gov (United States)

    Cristancho-Lacroix, Victoria; Kerhervé, Hélène; de Rotrou, Jocelyne; Rouquette, Alexandra; Legouverneur, Grégory; Rigaud, Anne-Sophie

    2013-12-06

    Informal caregivers (CGs) of patients with Alzheimer's disease are at risk of suffering from psychological and physical weakening. Several psychoeducational interventions have been designed to prevent stress and burden of caregivers. In France, despite health authorities' recommendations, to our knowledge there is no rigorously assessed Web-based psychoeducational program to date. The objective of our study was to assess the efficacy of a French Web-based psychoeducational program (called Diapason) with an unblinded randomized clinical trial. In this protocol, 80 informal caregivers of patients followed at Broca Hospital are recruited offline and randomized in the experimental condition (EC) or the control condition (CC). The volunteers in EC have to visit a closed online user group at least once a week and validate one new session of this fully automated Web program, during 12 weeks. Each week a new thematic is added to the website. The participants in the CC receive usual care, and have access to the Diapason program after their participation (6 months). Face-to-face evaluations for both groups are planned every 3 months (M0-M3 and M6). The main objective of this program is to provide CGs with information on the disease process, how to prevent psychological strain (using anticipation and relaxation techniques), and offering a virtual space (forum) to discuss with other caregivers. The primary outcome of this study is the self-perceived stress, while self-efficacy, burden, depression, and self-perceived health status are defined as secondary outcomes. Other variables that might have an impact on the program efficacy are collected. This protocol was accepted for funding. The enrollment began in October 2011, and participants currently recruited will finish their evaluations in January 2014. The results are expected for June 2014. Findings might provide empirical evidence on: (1) the feasibility of an Internet-based program in the French context, (2) the

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  2. A computed tomography study of Alzheimer's disease

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    OpenAIRE

    Tang, Jun

    2012-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  5. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  6. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study.

    Science.gov (United States)

    Acosta-Baena, Natalia; Sepulveda-Falla, Diego; Lopera-Gómez, Carlos Mario; Jaramillo-Elorza, Mario César; Moreno, Sonia; Aguirre-Acevedo, Daniel Camilo; Saldarriaga, Amanda; Lopera, Francisco

    2011-03-01

    Mild cognitive impairment (MCI) and pre-MCI have been proposed as stages preceding Alzheimer's disease (AD) dementia. We assessed descendants of individuals with a mutation in presenilin 1 (PSEN1) that causes familial AD, with the aim of identifying distinct stages of clinical progression to AD dementia. We retrospectively studied a cohort of descendants of carriers of the PSEN1 E280A mutation. Pre-dementia cognitive impairment was defined by a score 2 SD away from normal values in objective cognitive tests, and was subdivided as follows: asymptomatic pre-MCI was defined by an absence of memory complaints and no effect on activities of daily living; symptomatic pre-MCI was defined by a score on the subjective memory complaints checklist higher than the mean and no effect on activities of daily living; and MCI was defined by a score on the subjective memory complaints checklist higher than the mean, with no effect on basic activities of daily living and little or no effect on complex daily activities. Dementia was defined according to the diagnostic and statistical manual of mental disorders, fourth edition. Reference mean scores were those of participants who did not carry the PSEN1 E280A mutation. We used the Turnbull survival analysis method to identify ages at onset of each stage of the disease. We measured the time from birth until onset of the three pre-dementia stages, dementia, and death, and assessed decline in cognitive domains for each stage. Follow-up was from Jan 1, 1995, to Jan 27, 2010. 1784 patients were initially identified, 449 of whom were PSEN1 E280A carriers who had complete clinical follow-up. Median age at onset was 35 years (95% CI 30-36) for asymptomatic pre-MCI, 38 years (37-40) for symptomatic pre-MCI, 44 years (43-45) for MCI, and 49 years (49-50) for dementia. The median age at death was 59 years (95% CI 58-61). The median time of progression from asymptomatic to symptomatic pre-MCI was 4 years (95% CI 2-8), from symptomatic pre-MCI to

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

    Science.gov (United States)

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

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

  8. Alzheimer's disease due to loss of function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

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

  9. Rivastigmine for Alzheimer's disease.

    Science.gov (United States)

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

    2015-09-22

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

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

    KAUST Repository

    Gao, Zhao-Ming

    2015-06-11

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

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

    Directory of Open Access Journals (Sweden)

    Zhao-Ming Gao

    2015-06-01

    Full Text Available 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.

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  13. Outils microfluidiques pour la maladie d'Alzheimer: Etude de l'agrégation de l'amyloïde-B

    OpenAIRE

    Picot, Vincent

    2012-01-01

    The aging of our society leads to a development of neurodegenerative disease like Alzheimer's disease. Patients require an important caring by their family and specialized organisms. Moreover, the mechanisms which lead to the disease are not very well known yet, and progresses in the understanding of these should help to find new treatment. Memory and compartmental troubles associated to Alzheimer's disease come from neuronal and synaptic losses. A scenario proposed to explain those losses is...

  14. Clinical efficacy of lamotrigine and changes in the dosages of concomitantly used psychotropic drugs in Alzheimer's disease with behavioural and psychological symptoms of dementia: a preliminary open-label trial.

    Science.gov (United States)

    Suzuki, Hidenobu; Gen, Keishi

    2015-03-01

    We investigated the clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in lamotrigine therapy in Alzheimer's disease with behavioural and psychological symptoms of dementia (BPSD). This study was a 16-week, preliminary open-label trial. The subjects were 40 inpatients. The outcome measures assessed were BPSD and cognitive function. BPSD was assessed with the Neuropsychiatric Inventory (NPI) and cognitive function was assessed with the Mini-Mental State Examination. The changes in the dosages of concomitant psychotropic drugs were also assessed. Although the mean changes from baseline NPI scores and the two NPI subscales (anxiety and irritability) were significantly lower within the lamotrigine therapy group, no significant differences were found when we compared the lamotrigine therapy group to the control group. The mean decrease from baseline on the NPI agitation subscale, however, was significantly greater in the lamotrigine therapy group than in the control group (P < 0.05). Furthermore, the mean decrease from baseline in the diazepam-equivalent dose was significantly greater in the lamotrigine therapy group than in the control group (P < 0.05). The results of this study suggest that the administration of lamotrigine to patients with severe Alzheimer's disease with BPSD may be effective and may make it possible to avoid increasing the dosage of antipsychotic medications prescribed to elderly patients. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

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

    Science.gov (United States)

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

    2016-07-01

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

  16. Neuroimaging of Alzheimer's disease

    International Nuclear Information System (INIS)

    Matsuda, Hiroshi

    2005-01-01

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

  17. Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Sidharth Mehan

    2017-01-01

    Full Text Available Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington's disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity, resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease-like neurodegeneration.

  18. Exploring the role of microorganisms in the disease-like syndrome affecting the sponge Ianthella basta.

    Science.gov (United States)

    Luter, Heidi M; Whalan, Steve; Webster, Nicole S

    2010-09-01

    A disease-like syndrome is currently affecting a large percentage of the Ianthella basta populations from the Great Barrier Reef and central Torres Strait. Symptoms of the syndrome include discolored, necrotic spots leading to tissue degradation, exposure of the skeletal fibers, and disruption of the choanocyte chambers. To ascertain the role of microbes in the disease process, a comprehensive comparison of bacteria, viruses, fungi, and other eukaryotes was performed in healthy and diseased sponges using multiple techniques. A low diversity of microbes was observed in both healthy and diseased sponge communities, with all sponges dominated by an Alphaproteobacteria, a Gammaproteobacteria, and a group I crenarchaeota. Bacterial cultivation, community analysis by denaturing gradient gel electrophoresis (Bacteria and Eukarya), sequencing of 16S rRNA clone libraries (Bacteria and Archaea), and direct visual assessment by electron microscopy failed to reveal any putative pathogens. In addition, infection assays could not establish the syndrome in healthy sponges even after direct physical contact with affected tissue. These results suggest that microbes are not responsible for the formation of brown spot lesions and necrosis in I. basta.

  19. Cerebrospinal fluid markers of Alzheimer's disease

    NARCIS (Netherlands)

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

    1991-01-01

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

  20. Early psychosocial intervention in Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  1. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

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

    2012-01-01

    PURPOSE: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). METHODS: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

  2. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

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

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

    Science.gov (United States)

    Athanasopoulos, Dimitrios; Karagiannis, George; Tsolaki, Magda

    2016-09-01

    Alzheimer disease (AD) is a chronic neurodegenerative disease with no effective cure so far. The current review focuses on the epigenetic mechanisms of AD and how nutrition can influence the course of this disease through regulation of gene expression, according to the latest scientific findings. The search strategy was the use of scientific databases such as PubMed and Scopus in order to find relative research or review articles published in the years 2012-2015. By showing the latest data of various nutritional compounds, this study aims to stimulate the scientific community to recognize the value of nutrition in this subject. Epigenetics is becoming a very attractive subject for researchers because it can shed light on unknown aspects of complex diseases like AD. DNA methylation, histone modifications, and microRNAs are the principal epigenetic mechanisms involved in AD pathophysiology. Nutrition is an environmental factor that is related to AD through epigenetic pathways. Vitamin B-12, for instance, can alter the one-carbon metabolism and thus interfere in the DNA methylation process. The research results might seem ambiguous about the clinical role of nutrition, but there is strengthening evidence that proper nutrition can not only change epigenetic biomarker levels but also prevent the development of late-onset AD and attenuate cognition deficit. Nutrition might grow to become a preventive and even therapeutic alternative against AD, especially if combined with other antidementia interventions, brain exercise, physical training, etc. Epigenetic biomarkers can be a very helpful tool to help researchers find the exact nutrients needed to create specific remedies, and perhaps the same biomarkers can be used even in patient screening in the future. © 2016 American Society for Nutrition.

  4. Neuroinflammation in Alzheimer's disease

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  5. Diagnosis and treatment of Alzheimer's disease

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  6. Eye movements in Alzheimer's disease.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

    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. The Frisian Alzheimer's Disease Cohort study is a "real-life" study of the course of AD in patients (n=576) treated with pharmacological (ie, cholinesterase inhibitors) and nonpharmacological (ie, case management, respite care) interventions. Disease course was described by changes in cognition (Mini Mental State Examination, clock-drawing test) and number of types of professional care applying a repeated-measures analysis using a marginal model (population-based average model). In addition, behavioral and psychological symptoms, and proportions of nursing home admissions and deaths were investigated. During 3.5 years, the average Mini Mental State Examination decreased from 22.24 to 18.91, the clock-drawing test score increased from 3.38 to 4.05, the number of types of professional care increased from 0.85 to 2.64, and the patients with behavioral and psychological symptoms increased from 29.0% to 70.2%. The proportion of patients admitted to a nursing home was 40.8% and 41.0% died. Cognition and behaviour of AD patients deteriorated accompanied with an increase in care-dependency during 3.5 years. Nevertheless, compared with the precholinesterase inhibitor era, current pharmacological and nonpharmacological interventions appear to slow cognitive decline, which emphasizes that they seem to have a favorable effect.

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

    Science.gov (United States)

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

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

  9. Alzheimer's Caregivers: MedlinePlus Health Topic

    Science.gov (United States)

    ... Traveling with Your Loved One (Fisher Center for Alzheimer's Research Foundation) Abuse (Alzheimer's Association) Adapting Activities for People ... Relationships (Alzheimer's Association) Continuing Care ... (Fisher Center for Alzheimer's Research Foundation) Coping with Agitation and Aggression (National Institute ...

  10. Alzheimer disease and anesthesia.

    Science.gov (United States)

    Inan, Gözde; Özköse Satirlar, Zerrin

    2015-01-01

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

  11. Seven Stages of Alzheimer's

    Science.gov (United States)

    ... Dementias . Learn more: Daily Care and Behaviors Severe Alzheimer's disease (late-stage) Get support Late-stage care decisions can be some of the hardest families face. Connect with other caregivers who have been through the process on our ...

  12. Communication and Alzheimer's

    Science.gov (United States)

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

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

    Science.gov (United States)

    2013-02-08

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

  15. Mathematical model on Alzheimer's disease.

    Science.gov (United States)

    Hao, Wenrui; Friedman, Avner

    2016-11-18

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

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

    Science.gov (United States)

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

    2015-03-01

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

  17. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  18. Alzheimer's Disease Facts and Figures

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

  19. Alzheimer's Disease Facts and Figures

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    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 ...

  20. Alzheimer's Disease Facts and Figures

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

  1. Alzheimer's Disease Facts and Figures

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

  2. Alzheimer's Disease Facts and Figures

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

  3. Alzheimer's Disease Facts and Figures

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

  4. Alzheimer's Disease Facts and Figures

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

  5. Alzheimer's Disease Facts and Figures

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

  6. Alzheimer's Disease Facts and Figures

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

  7. Alzheimer's Disease Facts and Figures

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

  8. Alzheimer's Disease Facts and Figures

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

  9. Alzheimer's Disease Facts and Figures

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

  10. Alzheimer's Disease Facts and Figures

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

  11. Alzheimer's Disease Facts and Figures

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

  12. Alzheimer's Disease Facts and Figures

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

  13. Alzheimer's Disease Facts and Figures

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

  14. Alzheimer's Disease Facts and Figures

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

  15. Alzheimer's Disease Facts and Figures

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

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

  17. Alzheimer's Disease Facts and Figures

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

  18. Alzheimer's Disease Facts and Figures

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

  19. Alzheimer's Disease Facts and Figures

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

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  1. Alzheimer's Disease Facts and Figures

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

  2. Alzheimer's Disease Facts and Figures

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

  3. Down Syndrome and Alzheimer's Disease

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

  4. Alzheimer's Disease Facts and Figures

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

  5. Alzheimer's Disease Facts and Figures

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

  6. African-Americans and Alzheimer's

    Science.gov (United States)

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

  7. Alzheimer's Disease Facts and Figures

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

  8. JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

    Science.gov (United States)

    Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. © 2015 Wiley Periodicals, Inc.

  10. IDOSOS COM ALZHEIMER: UM ESTUDO DESCRITIVO

    Directory of Open Access Journals (Sweden)

    Ítala Thaise Aguiar Holanda

    2012-01-01

    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.

  11. How Alzheimer's Changes the Brain

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    Full Text Available ... Get YouTube Red. Working... Not now Try it free Find out why Close How Alzheimer's Changes the ... 4:22 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,695 ...

  12. Alzheimer's Disease Facts and Figures

    Medline Plus

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

  13. Epidemiology of Alzheimer Disease

    Science.gov (United States)

    Mayeux, Richard; Stern, Yaakov

    2012-01-01

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

  14. Music therapy is a potential intervention for cognition of Alzheimer?s Disease: a mini-review

    OpenAIRE

    Fang, Rong; Ye, Shengxuan; Huangfu, Jiangtao; Calimag, David P.

    2017-01-01

    Alzheimer?s Disease (AD) is a global health issue given the increasing prevalence rate and the limitations of drug effects. As a consequent, non-pharmacological interventions are of importance. Music therapy (MT) is a non-pharmacological way with a long history of use and a fine usability for dementia patients. In this review, we will summarize different techniques, diverse clinical trials, and the mechanisms of MT as it is helpful to the cognition in AD, providing reference for future resear...

  15. Aphasia(s) in Alzheimer.

    Science.gov (United States)

    Teichmann, M; Ferrieux, S

    2013-10-01

    Language disorders of degenerative origin are frequently tied to Alzheimer disease (AD) the different variants of which can result in primary and secondary aphasia syndromes. More specifically, Alzheimer pathology can primarily erode frontal, temporal or parietal language cortices resulting in three genuine AD language variants which account for about 30% of primary degenerative aphasias. Likewise, it can spread from non-language to language cortices leading to secondary language disorders like in typical amnesic AD and in several atypical AD variants. This paper reviews the whole set of AD variants by characterising their impact on the neural language system and on linguistic functioning. It also provides cues for diagnostic strategies which are essential for linguistic, syndromic and nosological patient classification, for adequate clinical follow-up and for guiding language rehabilitation. Such diagnostic approaches, founded on detailed linguistic phenotyping while integrating anatomical and neuropathological findings, also represent a crucial issue for future drug trials targeting the physio-pathological processes in degenerative aphasias. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2010-02-01

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

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

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne

    2010-01-01

    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....

  18. 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

    2005-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Martine Jacquier

    2001-03-01

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

  20. Inflammation and Alzheimer's disease

    NARCIS (Netherlands)

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

    2000-01-01

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

  1. Mitophagy and Alzheimer's Disease

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

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

    Science.gov (United States)

    Villegas, Sandra

    2015-07-20

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

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Predicting progression of Alzheimer's disease.

    Science.gov (United States)

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

    2010-02-23

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

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

    Directory of Open Access Journals (Sweden)

    Mahsan Assadi

    2011-11-01

    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, memory.in 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.

  7. Alzheimer's and Dementia Testing for Earlier Diagnosis

    Science.gov (United States)

    ... for Earlier Diagnosis What if we could diagnose Alzheimer's before symptoms started? The hope is, future treatments ... diagnosis is among the most active areas in Alzheimer's science, and funding from the Alzheimer's Association has ...

  8. CT study in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Heii; Kobayashi, Kazunari; Ikeda, Kenji; Nagao, Yoshiko; Ogihara, Ryuji; Kosaka, Kenji (Tokyo Metropolitan Matsuzawa Hospital (Japan))

    1983-01-01

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

  9. REVIEW: Curcumin and Alzheimer's disease.

    Science.gov (United States)

    Hamaguchi, Tsuyoshi; Ono, Kenjiro; Yamada, Masahito

    2010-10-01

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

  10. [Palliative care and Alzheimer disease].

    Science.gov (United States)

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

    2009-06-01

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

  11. Mucosal disease-like syndrome in a calf persistently infected by Hobi-like pestivirus.

    Science.gov (United States)

    Decaro, Nicola; Lanave, Gianvito; Lucente, Maria Stella; Mari, Viviana; Varello, Katia; Losurdo, Michele; Larocca, Vittorio; Bozzetta, Elena; Cavaliere, Nicola; Martella, Vito; Buonavoglia, Canio

    2014-08-01

    A calf persistently infected with Hobi-like pestivirus displayed severe clinical signs and subsequently died. Gross lesions and histopathological changes were suggestive of hemorrhagic and necrotic inflammation involving several tissues. A Hobi-like pestivirus pair was isolated from the dead calf, i.e., cytopathogenic (CP) and noncytopathogenic (NCP) strains strictly related to each other and to Italian prototype isolates at the genetic level. Two biotype-specific real-time reverse transcription-PCR assays determined the time of the emergence of the CP virus as 1 month before the calf's death. This highest RNA titers were reached in lymphoid and nervous system tissues, whereas only traces of CP viral RNA were found in blood. In contrast, great NCP virus loads were present in all tissues and biological fluids. The present report provides new insights into the pathogenesis and molecular mechanisms of this emerging group of pestiviruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Cognitive Abilities of Alzheimer's Patients: Perceptions of Black and White Caregivers

    Science.gov (United States)

    Burns, Robert; Nichols, Linda O.; Graney, Marshall J.; Martindale-Adams, Jennifer; Lummus, Allan

    2006-01-01

    This study compared Black (n = 97) and White (n = 143) family caregivers regarding the relationship between subjective and objective cognitive assessments of Alzheimer's patients from the Memphis site of the NIA/NINR Resources for Enhancing Alzheimer's Caregivers Health (REACH) randomized clinical trial. Black and White caregivers' subjective…

  13. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria

    NARCIS (Netherlands)

    Dubois, B; Feldman, H.H.; Jacova, C.; Hampel, H.; Molinuevo, J.L.; Blennow, K.; Dekosky, S.T.; Gauthier, S.; Selkoe, D.; Bateman, R.; Cappa, S.; Crutch, S.; Engelborghs, S.; Frisoni, G. B.; Fox, N.C.; Galasko, D.; Habert, M.O.; Jicha, G.A.; Nordberg, A.; Pasquier, F.; Rabinovici, G.; Robert, P.; Rowe, C.; Salloway, S.; Sarazin, M.; Epelbaum, S.; de Souza, L.C.; Vellas, B.; Visser, P.J.; Schneider, L.; Stern, Y.; Scheltens, P.; Cummings, J.L.

    2014-01-01

    In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    International Nuclear Information System (INIS)

    Yin Jianzhong; Wang Jianli; Yang Qingxian; Qi Ji

    2008-01-01

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

  16. How Alzheimer's Changes the Brain

    Medline Plus

    Full Text Available ... How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National Institute On Aging? Cancel Unsubscribe Working... Subscribe Subscribed Unsubscribe 6K Loading... ...

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

    Science.gov (United States)

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

    2015-04-01

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

  18. Oligodendrocytes and Alzheimer's disease.

    Science.gov (United States)

    Cai, Zhiyou; Xiao, Ming

    2016-01-01

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

  19. The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population.

    Science.gov (United States)

    Baine, Fiona K; Krause, Amanda; Greenberg, L Jacquie

    2016-01-01

    Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. © 2016 S. Karger AG, Basel.

  20. The etiology of Ebola virus disease-like illnesses in Ebola virusnegative patients from Sierra Leone.

    Science.gov (United States)

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

    2016-05-10

    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.

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

    Science.gov (United States)

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

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Apathy in Alzheimer's disease

    OpenAIRE

    Nobis, L; Husain, M

    2017-01-01

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

  4. 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.

    Science.gov (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

    2014-12-01

    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.

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

    Science.gov (United States)

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

    2014-10-01

    The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    Lino, Angelina Maria Martins; Spera, Raphael Ribeiro; de Campos, Fernando Peixoto Ferraz; Freitas, Christian Henrique de Andrade; Garcia, Márcio Ricardo Taveira; Lopes, Leonardo da Costa; Prokopowitsch, Aleksander Snioka

    2014-01-01

    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/3 wks) 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).

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

    Directory of Open Access Journals (Sweden)

    Angelina Maria Martins Lino

    2014-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Víctor T. Pérez Martínez

    2005-08-01

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

  10. 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

    2012-06-01

    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

  11. The application of lipidomics to biomarker research and pathomechanisms in Alzheimer's disease.

    Science.gov (United States)

    Wong, Matthew W; Braidy, Nady; Poljak, Anne; Sachdev, Perminder S

    2017-03-01

    Alzheimer's disease is the most common cause of dementia. There are still no disease modifying treatments that can cure or slow disease progression. Recently, Alzheimer's disease researchers have attempted to improve early detection and diagnostic criteria for Alzheimer's disease, with the rationale that treatment of disease, or even prevention, may be more successful during the early preclinical stages of Alzheimer's disease when neurodegenerative damage is not as widespread. As the brain has a high lipid content, lipidomics may offer novel insights into the underlying pathogenesis of Alzheimer's disease. This review reports on recent developments in the relatively unexplored field of lipidomics in Alzheimer's disease, including novel biomarkers and pathomechanisms of Alzheimer's disease. Numerous biomarker panels involving phospholipids and sphingolipids have been proposed, indicating perturbed lipid metabolism in early stages of Alzheimer's disease. Future strategies targeting these metabolic changes through dietary supplementation could have therapeutic benefits in at-risk individuals. Dysregulated lipid metabolism could reflect pathological changes in synaptic function and neuronal membranes, leading to cognitive decline. However, extensive validation in large independent cohorts is required before lipid biomarkers can be used clinically to assess Alzheimer's disease risk and progression.

  12. Profiling of Alzheimer's disease patients in Puerto Rico: A comparison of two distinct socioeconomic areas.

    Science.gov (United States)

    Camacho-Mercado, Clara L; Figueroa, Raúl; Acosta, Heriberto; Arnold, Steven E; Vega, Irving E

    2016-01-01

    The Latino/Hispanic community in the United States is at higher risk of developing Alzheimer's disease than other ethnic groups. Specifically, Caribbean Hispanics showed a more severe Alzheimer's disease symptomatology than any other ethnic group. In a previous study, we demonstrated that the mortality rate associated with Alzheimer's disease in Puerto Rico is higher than that reported in the United States. Moreover, the mortality rate associated with Alzheimer's disease was higher among Puerto Rican living in Puerto Rico than those in the mainland United States. There is also a differential geographical distribution of mortality rate associated with Alzheimer's disease in Puerto Rico, which may be associated with differential socioeconomic status and/or access to healthcare. However, there is no information regarding the clinical profile of Alzheimer's disease patients in Puerto Rico. Here, we present the results of a retrospective study directed to profile Alzheimer's disease patients clustered into two groups based on areas previously determined with low (Metro Region) and high (Northwest-Central Region) mortality rate associated with Alzheimer's disease in Puerto Rico. Significant difference in the age-at-diagnosis and years of education was found among patients within the two studied regions. Despite these differences, both regions showed comparable levels of initial and last Mini Mental State Examination scores and rate of cognitive decline. Significant difference was also observed in the occurance of co-morbidities associated with Alzheimer's disease. The differential profile of Alzheimer's disease patients correlated with differences in socioeconomic status between these two regions, suggesting that covariant associated with social status may contribute to increased risk of developing Alzheimer's disease. Further studies should be conducted to determine the role of socioeconomic factors and healthy living practices as risk factors for Alzheimer's disease.

  13. How Alzheimer's Changes the Brain

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    Full Text Available ... 556,252 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 18,542 views ... views 5:15 5 Signs You'll Get Alzheimer's Disease - Dr. Russell Blaylock Offers Crucial Advice. - Duration: 33: ...

  14. Alzheimer's Disease Facts and Figures

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

  15. Alzheimer's Disease Facts and Figures

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

  16. How Alzheimer's Changes the Brain

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    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 5:15 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,695 ...

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    Full Text Available ... suggested video will automatically play next. Up next What you can do to prevent Alzheimer's | Lisa Genova - ... 8:54. Osmosis 310,083 views 8:54 What Is Alzheimer's Disease? - Duration: 3:15. AboutAlzOrg 539, ...

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    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 3:15 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,411 ...

  19. How Alzheimer's Changes the Brain

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    Full Text Available ... 728 views 8:54 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni Wombaker 923,094 views 54:55 Kids Meet a Woman with Alzheimer's | Cut - Duration: 5:15. Cut 6,969,600 ...

  20. Alzheimer's Disease Facts and Figures

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

  1. How Alzheimer's Changes the Brain

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    Full Text Available ... The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni Wombaker 923,815 ... 37 Day in the Life of an Alzheimer's Caregiver: Heartbreaking - Duration: 4:39. DavidNazarNews 30,944 views ...

  2. Alzheimer's Disease Facts and Figures

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

  3. How Alzheimer's Changes the Brain

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    Full Text Available ... 599,357 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 20,532 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  4. How Alzheimer's Changes the Brain

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    Full Text Available ... free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ... Health Journey 169,151 views 2:20 Inside the Brain: Unraveling the Mystery of Alzheimer's Disease - Duration: 4: ...

  5. and late onset Alzheimer's disease

    African Journals Online (AJOL)

    Yomi

    2012-03-15

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

  6. How Alzheimer's Changes the Brain

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    Full Text Available ... to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show less ... Mystery of Alzheimer's Disease - Duration: 4:22. Knoxville News Sentinel 34,722 views 4:22 Alzheimer's and ...

  7. How Alzheimer's Changes the Brain

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    Full Text Available ... 569,749 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 19,280 views ... 827 views 5:15 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  8. How Alzheimer's Changes the Brain

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    Full Text Available ... 561,781 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 18,848 views ... views 5:15 5 Signs You'll Get Alzheimer's Disease - Dr. Russell Blaylock Offers Crucial Advice. - Duration: 33: ...

  9. How Alzheimer's Changes the Brain

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    Full Text Available ... 632,620 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 21,392 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

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  11. Alzheimer's Disease Facts and Figures

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

  12. How Alzheimer's Changes the Brain

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    Full Text Available ... 579,477 views 13:57 2-Minute Neuroscience: Alzheimer's Disease - Duration: 2:01. Neuroscientifically Challenged 19,614 views 2:01 The 7 Stages of Alzheimer's Disease Through a Caregiver's Eyes - Duration: 54:55. Toni ...

  13. Alzheimer's Disease Facts and Figures

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

  14. How Alzheimer's Changes the Brain

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    Full Text Available ... ideas to treat and prevent the disease. Category Science & Technology License Standard YouTube License Show more Show ... 9:57 Your Amazing Brain - Dementia Explained - Alzheimer's Research UK - Duration: 4:58. AlzheimersResearch UK 16,411 ...

  15. Alzheimer's Disease Facts and Figures

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

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

    Science.gov (United States)

    Sapra, Mamta; Kim, Kye Y

    2009-06-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  18. The biological substrates of Alzheimer's disease

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  19. Scintigraphic appearance of Alzheimer diesase

    International Nuclear Information System (INIS)

    Holman, B.L.; Johnson, K.A.

    1991-01-01

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

  20. Genetic Aspects of Alzheimer Disease

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

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

  2. Characteristics of mild cognitive impairment tending to convert into Alzheimer's disease or dementia with Lewy bodies: A follow-up study in a memory clinic.

    Science.gov (United States)

    Kondo, Daizo; Ota, Kazumi; Kasanuki, Koji; Fujishiro, Hiroshige; Chiba, Yuhei; Murayama, Norio; Sato, Kiyoshi; Hirayasu, Yoshio; Arai, Heii; Iseki, Eizo

    2016-10-15

    To determine characteristics of MCI that can predict whether patients will go on to develop AD or DLB. Ninety-three patients diagnosed with MCI underwent neuropsychological and neuroimaging examinations, and were followed-up for a mean of 44.9±19.3months. They were divided into four MCI subtypes (amnestic/non-amnestic MCI, single/multiple domain) according to neuropsychological findings, and into three other MCI categories (AD-type PET, DLB-type PET, and unknown-type PET) based on (18)F-fluorodeoxyglucose PET findings. Patients who were eventually diagnosed with AD, DLB, other dementia, or remained MCI were analyzed in relation to the groups to which they had initially been allocated at the MCI stage. Clinical diagnosis after follow-up determined AD in 21 patients (22.6%), DLB in 12 patients (12.9%), other dementia in 2 patients (2.2%), and non-converter in 58 patients (62.3%). Amnestic single-domain MCI and AD-type PET tended to convert into AD. Amnestic multiple-domain MCI and DLB-type PET tended to convert into DLB. A few patients with AD-type PET later developed DLB, and some with DLB-type PET later developed AD. Predicting which type of dementia a person with MCI will later develop might be possible based on early assessment with clinical symptoms in conjunction with neuropsychological and (18)F-fluorodeoxyglucose PET findings. Copyright © 2016. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Georgia eGleason

    2011-05-01

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

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

    Science.gov (United States)

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

  5. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    Science.gov (United States)

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

  6. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana

    2017-01-01

    BACKGROUND: Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap betwee...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Science.gov (United States)

    ... have not demonstrated that, over the long term, health or lifestyle factors can prevent or slow Alzheimer's disease or age-related cognitive decline. Similarly, clinical trial results do not support ...

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics12

    Science.gov (United States)

    2016-01-01

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

  11. The impact of educational experiences on nursing students' knowledge and attitudes toward people with Alzheimer's disease: A mixed method study.

    Science.gov (United States)

    Kimzey, Michelle; Mastel-Smith, Beth; Alfred, Danita

    2016-11-01

    As the population ages, the effects of Alzheimer's disease will be felt by all nurses. Providing proper care for people with Alzheimer's disease is difficult and requires specific skills, attitudes, and knowledge. Limited data exists regarding nursing students' attitudes and knowledge toward people with Alzheimer's disease, whether undergraduate education prepares students to care for this population, or the best methods to support students in learning in an innovative and interactive environment. The aim of this study was to determine the effect of different educational experiences on nursing students' knowledge and attitudes toward people with Alzheimer's disease and to explore nursing students' knowledge and attitudes surrounding the care of people with Alzheimer's disease. A convergent mixed method design. A three group (Alzheimer's disease clinical experience, online learning module, and no dementia-specific intervention), pretest and posttest design served as the quantitative arm of the study. A focus group discussion with themes extracted served as the qualitative piece of the study. College of Nursing in North Texas. Convenience sample of 94 senior level nursing students enrolled in the undergraduate nursing program's Community Health course. Students completed pre and posttest surveys which included Alzheimer's Disease Knowledge Scale, Dementia Attitudes Scale, and demographic questionnaire. Content analysis was conducted on focus group responses to qualitative interview questions. The Alzheimer's disease clinical group experienced increased knowledge and improved attitudes toward people with Alzheimer's disease compared with students who completed the online module or had no dementia-specific intervention. Four themes emerged from focus group data: Basic Alzheimer's disease knowledge, need for Alzheimer's disease experiential learning, negative feelings related to behaviors, and appropriate responses to behavioral and psychological symptoms of dementia

  12. Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

    Science.gov (United States)

    Epperly, Ted; Dunay, Megan A; Boice, Jack L

    2017-06-15

    Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

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

    Science.gov (United States)

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

    2012-02-01

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

  14. Alzheimer's disease due to loss of function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses....... The amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease. Here, a new loss-of-function hypothesis is synthesized that accounts...

  15. [Aβ immunotherapy for Alzheimer's disease].

    Science.gov (United States)

    Sakai, Kenji; Yamada, Masahito

    2013-04-01

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

  16. Effects of medicinal plants on Alzheimer's disease and memory deficits

    Directory of Open Access Journals (Sweden)

    Muhammad Akram

    2017-01-01

    Full Text Available Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.

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

    Science.gov (United States)

    Gómez Gallego, M; Gómez García, J

    2017-06-01

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

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

    Science.gov (United States)

    Claassen, Jurgen A H R

    2015-09-15

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

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

    Science.gov (United States)

    2017-05-11

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

  20. Alzheimer's disease: An alternative approach

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2017-01-01

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

  1. Ayurvedic Profiling of Alzheimer's Disease.

    Science.gov (United States)

    Bredesen, Dale E; Rao, Rammohan V

    2017-05-01

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

  2. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

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

    2014-01-01

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

  3. Molecular subtypes of Alzheimer's disease.

    Science.gov (United States)

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

    2018-02-19

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

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

    International Nuclear Information System (INIS)

    Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In

    1988-01-01

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

  5. What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

    OpenAIRE

    Wallace, Robyn A; Dalton, Arthur J

    2011-01-01

    The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of ?-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible fo...

  6. Alzheimer's Disease Facts and Figures

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

  7. Alzheimer's Disease Facts and Figures

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

  8. Alzheimer's Disease Facts and Figures

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

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

  • How Alzheimer's Changes the Brain

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    1. How Alzheimer's Changes the Brain

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      Full Text Available ... Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe from National ... minute video shows how Alzheimer’s affects the human brain and looks at promising ideas to treat and ...

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

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

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    6. Alzheimer's Disease Facts and Figures

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

    7. Alzheimer's Disease Facts and Figures

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

    8. How Alzheimer's Changes the Brain

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      Full Text Available ... it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... Unsubscribe ... Bredesen, MD - Duration: 1:13:27. Silicon Valley Health Institute 94,011 views 1:13:27 Inside ...

    9. Alzheimer's Disease Facts and Figures

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

    10. Alzheimer's Disease Facts and Figures

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

    11. How Alzheimer's Changes the Brain

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      Full Text Available ... Queue Queue __count__/__total__ Find out why Close How Alzheimer's Changes the Brain National Institute On Aging ... Aug 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at ...

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

      Science.gov (United States)

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

      2013-01-01

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

    14. How Alzheimer's Changes the Brain

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    15. Alzheimer's Disease Facts and Figures

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

    16. Alzheimer's Disease Facts and Figures

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

    17. Alzheimer's Disease Facts and Figures

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

    18. Alzheimer's Disease Facts and Figures

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

    19. Alzheimer's Disease Facts and Figures

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

    20. How Alzheimer's Changes the Brain

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    1. Alzheimer's: From Caring to Commitment

      Science.gov (United States)

      ... Current Issue Past Issues Home Current issue contents Alzheimer's: From Caring to Commitment From Caring to Commitment ... Caring to Commitment During her sister’s battle with Alzheimer’s, Anne Murphy stayed by her side and continues ...

    2. How Alzheimer's Changes the Brain

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      ... Try it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... ... 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ...

    3. How Alzheimer's Changes the Brain

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      Full Text Available ... Try it free Find out why Close How Alzheimer's Changes the Brain National Institute On Aging Loading... ... 23, 2017 This 4-minute video shows how Alzheimer’s affects the human brain and looks at promising ...

    4. Alzheimer's Disease Facts and Figures

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

    5. Alzheimer's Disease Facts and Figures

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

    6. Neurogenesis and Alzheimer's Disease

      Directory of Open Access Journals (Sweden)

      Philippe Taupin

      2006-01-01

      Full Text Available Alzheimer's disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

    7. The Danish Alzheimer intervention study

      DEFF Research Database (Denmark)

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

      2011-01-01

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

    8. Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

      Directory of Open Access Journals (Sweden)

      Kyung Won Park

      Full Text Available Studies investigating the impact of white matter hyperintensities (WMHs on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog from the baseline to the end of the study.Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46 during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70 and group 2 (-0.23±5.98 after the 24-week rivastigmine patch therapy (p = 0.378. The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037. The rates of adverse events (AEs (42.6 vs. 40.3% and discontinuation due to AEs (10.3% vs. 4.3% did not differ between the groups.Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.ClinicalTrials.gov NCT01380288.

    9. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer's Association Research Roundtable Workgroup

      NARCIS (Netherlands)

      Sperling, R.A.; Jack, C.R.; Black, S.E.; Frosch, M.P.; Greenberg, S.M.; Hyman, B.T.; Scheltens, P.; Carrillo, M.C.; Thies, W.; Bednar, M.M.; Black, R.S.; Brashear, H.R.; Grundman, M.; Siemers, E.R.; Feldman, H.H.; Schindler, R.J.

      2011-01-01

      Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened

    10. Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.

      Science.gov (United States)

      Callahan, Christopher M; Boustani, Malaz A; Schmid, Arlene A; LaMantia, Michael A; Austrom, Mary G; Miller, Douglas K; Gao, Sujuan; Ferguson, Denisha Y; Lane, Kathleen A; Hendrie, Hugh C

      2017-02-07

      Alzheimer disease results in progressive functional decline, leading to loss of independence. To determine whether collaborative care plus 2 years of home-based occupational therapy delays functional decline. Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950). Urban public health system. 180 community-dwelling participants with Alzheimer disease and their informal caregivers. All participants received collaborative care for dementia. Patients in the intervention group also received in-home occupational therapy delivered in 24 sessions over 2 years. The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL); performance-based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM). At baseline, clinical characteristics did not differ significantly between groups; the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The intervention group received a median of 18 home visits from the study occupational therapists. In both groups, ADCS ADL scores declined over 24 months. At the primary end point of 24 months, ADCS ADL scores did not differ between groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not definitively demonstrate between-group differences in mean SPPB or SPSM values. The results of this trial are indeterminate and do not rule out potential clinically important effects of the intervention. The authors could not definitively demonstrate whether the addition of 2 years of in-home occupational therapy to a collaborative care management model slowed the rate of functional decline among persons with Alzheimer disease. This trial underscores the burden undertaken by caregivers as they provide care for family members with Alzheimer disease and the difficulty in slowing functional decline. National Institute on Aging.

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

      Science.gov (United States)

      Dubois, Bruno

      2013-01-01

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

    12. Clinical impact of (11)C-Pittsburgh compound-B positron emission tomography carried out in addition to magnetic resonance imaging and single-photon emission computed tomography on the diagnosis of Alzheimer's disease in patients with dementia and mild cognitive impairment.

      Science.gov (United States)

      Omachi, Yoshie; Ito, Kimiteru; Arima, Kunimasa; Matsuda, Hiroshi; Nakata, Yasuhiro; Sakata, Masuhiro; Sato, Noriko; Nakagome, Kazuyuki; Motohashi, Nobutaka

      2015-12-01

      The purpose of this study was to evaluate the clinical impact of addition of [(11)C]Pittsburgh compound-B positron emission tomography ((11)C-PiB PET) on routine clinical diagnosis of Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI), and to assess diagnostic agreement between clinical criteria and research criteria of the National Institute on Aging-Alzheimer's Association. The diagnosis in 85 patients was made according to clinical criteria. Imaging examinations, including both magnetic resonance imaging and single-photon emission computed tomography/computed tomography to identify neuronal injury (NI), and (11)C-PiB PET to identify amyloid were performed, and all subjects were re-categorized according to the research criteria. Among 40 patients with probable AD dementia (ProAD), 37 were NI-positive, 29 were (11)C-PiB-positive, and 27 who were both NI- and (11C-PiB-positive were categorized as having 'ProAD dementia with a high level of evidence of the AD pathophysiological process'. Among 20 patients with possible AD dementia (PosAD), 17 were NI-positive, and six who were both NI- and (11)C-PiB-positive were categorized as having 'PosAD with evidence of the AD pathophysiological process'. Among 25 patients with MCI, 18 were NI-positive, 13 were (11)C-PiB-positive, and 10 who were both NI- and (11)C-PiB-positive were categorized as having 'MCI due to AD-high likelihood'. Diagnostic concordance between clinical criteria and research criteria may not be high in this study. (11)C-PiB PET may be of value in making the diagnosis of dementia and MCI in cases with high diagnostic uncertainty. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

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

      Directory of Open Access Journals (Sweden)

      Antônio Lúcio Teixeira-Jr

      2006-09-01

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

    14. The road to restoring neural circuits for the treatment of Alzheimer's disease.

      Science.gov (United States)

      Canter, Rebecca G; Penney, Jay; Tsai, Li-Huei

      2016-11-10

      Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest that cognitive decline is the result of a complex pathophysiology and that targeting amyloid-alone may not be sufficient to treat Alzheimer's disease. Instead, a broad outlook on neural-circuit-damaging processes may yield insights into new therapeutic strategies for curing memory loss in the disease.

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

      Science.gov (United States)

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

      2016-07-29

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

    16. Grief and Loss as Alzheimer's Progresses

      Science.gov (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 ...

    17. Imagine stopping the progression of Alzheimer's

      Science.gov (United States)

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

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

      Science.gov (United States)

      Potter, Pamela E

      2010-09-01

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

    19. Down syndrome and Alzheimer's disease: Common pathways, common goals.

      Science.gov (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

      2015-06-01

      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. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

    20. A conceptual framework and ethics analysis for prevention trials of Alzheimer Disease.

      Science.gov (United States)

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

      2013-11-01

      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. Copyright © 2013 Elsevier Ltd. All rights reserved.