B Winblad

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..Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD...

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..Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated...

..Patients who received continuous pharmacologic treatment from the outset generally had better long-term outcomes than those who received placebo in the double-blind phase of these trials...

..The later findings are results from the M-BEST study, which is briefly rewieved here with some of the epidemiological, socioeconomical and clinical implications of such therapy...

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..These behavioral benefits were associated with reduced caregiver distress and translated into reduced caregiver time. These benefits would be expected to make an important difference to the quality of life of patients and caregivers...

..To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD...

..Thus, the health economics of dementia is an extremely complex area of study that is rapidly growing, due to the likelihood that cost-effectiveness will form the basis for future reimbursement decisions...

..Evidently, CD28 is required for interaction with B7 to regulate the activation of T and B cells that initiates development of EAN...

..These data support the long-term efficacy and safety of donepezil...

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..This study confirms that dementia and cognitive impairment are the main contributors to institutionalization in the elderly, independently of their sociodemographic status, social network, or functional status...

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..To examine the relation between serum levels of homocysteine (tHcy) and holotranscobalamin (holoTC), the active fraction of vitamin B12, and risk of incident Alzheimer disease (AD) in a sample of Finnish community-dwelling elderly...

..Together, the data show that gamma-secretase complexes containing PS1-caspCTF are active, and suggest that this proteolytic activity is also important in dying cells and may affect the progression of AD...

..The Kungsholmen project is a longitudinal study of ageing and dementia conducted in Stockholm in 1987. In a 1994-96 follow-up, 804 subjects had their blood samples analyzed for lead...

..BACKGROUND and..

..Thus, manipulation of CTLA-4/B7 costimulatory pathway by CTLA-4 blockade can promote autoreactivity and break the relative tolerance to peripheral autoantigen P0 in resistant B6 mice...

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..To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors...

..It is conceivable that in the absence of glial elements, such as in the present neuroblastoma cell line, beta-amyloid triggers the toxicity through a direct action and/or through the production of other harmful molecules...

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..05). Taken together, these findings imply that apoE modulates hippocampal damage induced by KA and found early in the sequence of human Alzheimer's brain changes, by modulating microglial activation...

..This study aimed to explore the association between work complexity factors at midlife and dementia risk in late life under the hypothesis that high work complexity may modulate the increased dementia risk due to low education...

..These results indicate that nicergoline can modulate alpha-secretase APP processing by a PKC dependent mechanism that is likely to involve the gamma and epsilon isoforms of this enzyme...

..These findings suggest that slowing in fast EEG frequencies during chronic treatment with AChE inhibitors may provide an early indicator of declining treatment efficiency...

..The specific change in the effect of a low concentration of Gpp[NH]p on the binding could indicate the loss of Ca2+/calmodulin-sensitive AC isoforms in AD...

..The authors' goal was to examine whether individuals diagnosed as having major depression experienced greater levels of depressive symptoms and cognitive dysfunction up to 3 years before the clinical diagnosis was rendered...

..In conclusion, PTEN inhibition gives a mild reversal of TNFalpha- but not HNE-induced cell death via the PI3K pathway...

..Thus, 100 microM zinc might activate PKB, GSK-3beta, ERK1/2, JNK, p38 and p70S6K, that are consequently involved in tau changes in SH-SY5Y cells...

..These results indicate that a zinc-induced anti-apoptotic response in SH-SY5Y cells likely occurs through ERK1/2...

..These findings indicate that there are very similar routes for Abeta and AICD formation but that FAD-linked mutations in APP primarily affect gamma-secretase-mediated Abeta42 formation, and not AICD signaling...

..These results denote the disparity of aging and gender in KA-induced hippocampal neurodegeneration and aged female mice are more sensitive to the excitotoxicity...

..Midlife high blood pressure is linked to late-life dementia. We sought to investigate the temporal relation of blood pressure to the risk of dementia and Alzhei-mer's disease (AD) among older adults...

..The risk effect of APOE epsilon 4 allele for Alzheimer's disease is acknowledged, whereas the putative protective effect of epsilon 2 allele remains in debate...

..These results indicate a possible role for NT-3 in synaptic plasticity...

..We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration...

..These effects could contribute to the reported PKC alterations seen in AD. However, it is unlikely that the contribution of different apoE isoforms to AD pathology occurs via effects on APP processing...

..Both stroke and the apolipoprotein E (APOE) epsilon4 allele increase the risk of dementia. However, the interaction between stroke and APOE on dementia is still unclear. We addressed this topic by using a longitudinal design...

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..Measures of temporoparietal cerebral metabolism and visuospatial function may aid in predicting the evolution to AD for patients with MCI...

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..The Tg6590 transgenic rat line should prove a suitable model of early AD for advanced studies including serial cerebrospinal fluid sampling, electrophysiology, neuroimaging or complex behavioural testing...

..A p70 S6 kinase modulated up-regulation of tau translation might contribute to PHF-tau accumulation in neurons with neurofibrillary changes...

..This novel localization of NCT, PS1, APH-1, and PEN-2 expands the role and importance of gamma-secretase activity to mitochondria...

..Thus, Abeta neurotoxicity might be mediated by oxidation of GRX1 or TRX1 and subsequent activation of the ASK1 cascade. Deregulation of GRX1 and TRX1 antioxidant systems could be important events in AD pathogenesis...

..To determine the prevalence of psychotropic drug use in very old persons with and without dementia in two time periods, and describe the patterns of psychotropic drug use between institutions and non-institutions...

..To investigate whether cognitive function is related to incidence of stroke...

..We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP...

..To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence...

..23; 95% CI 0.03-1.68). This could be due to the small samples in our study, or to comorbidity contributing to the development of dementia in this elderly population...

..Furthermore, the Pp genotype frequency was found to be significantly increased in Finnish women with sporadic AD. We, thus, conclude that the ESR1 gene may have a role in the development of AD in females...

..Available data show that there is support for a view that treatment is cost-neutral or perhaps cost saving which in combination with positive effects in terms of efficacy may indicate cost-effectiveness...

..e., PARP and gelsolin), simultaneous with minimum detectable caspase-3 activation. Therefore, alternative cleavage of PS1 may play an important role for the regulation of the proteolytic cascade activated during apoptosis...

..Our findings may suggest that in the frontal cortex, GAP-43 levels decline as a consequence of the synaptic degeneration, while in the hippocampus, sprouting processes, involving GAP-43, are active...

..This question is relevant both for understanding the pathogenetic mechanism of the dementias and for the public health prospective because of the increasing number of 85-year-old or older persons in our population...

..It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD...

..Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele...

..Furthermore, Hsp27 might also be involved in AD pathology by aggravating MT disruption by tau phosphorylation...

..This animal model could provide a valuable tool for exploring the role of excitotoxicity in neuropathological conditions and should be further evaluated in gene-targeting studies of neurodegenerative diseases...

..Furthermore, the administration of alpha-MSH resulted in a similar increase in cell viability, supporting the hypothesis that administration of alpha-MSH has rescuing effects on neurons subjected to excitotoxic insults...

..Assessments of levels of these abnormal proteins by dot blots may serve as a useful complement to the morphological evaluations in diagnosis of AD...

..There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis...

..The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH...

..The aim of the current study was to explore the separate and combined effects of neuroticism and extraversion on the risk of dementia, and to examine whether lifestyle factors may modify this association...

..These observations call for further studies on the potential role of Rolipram in the treatment of autoimmune diseases...

..CONCLUSIONS: Brain zinc accumulation is a prominent feature of advanced Alzheimer disease (AD) and is biochemically linked to brain amyloid beta-peptide accumulation and dementia severity in AD...

..Using a novel unbiased quantitative method, we were able to describe significant oligodendroglial loss in the PO but the pathogenic mechanism behind remains unknown...

..To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI)...

..This study aimed to clarify the association between work-related physical activity and dementia/AD...

..Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals...

..At the moment it is also possible to delineate some preventative strategies for dementia...

..From the Kungsholmen project in Sweden, there are indications that the postponement between MCI and manifest dementia may result in short-term benefits (a few years) of about SEK50,000 (5300 US dollars)...

..These results suggest that the role of IL-18 in excitotoxic injury in IL-18 deficient mice may be overcompensated by increased IL-12 secretion...

..The physical health correlates of mild cognitive impairment (MCI) in the older individual are poorly known. The aim of this study was to investigate the relationship between physical health and MCI with population data...

..This technique could be useful for screening and testing of pharmacological compounds relevant to neurodegenerative disorders...

..Local skin tolerability was good. The transdermal patch with rivastigmine may offer additional therapeutic benefits and may prove to be the best delivery system for this drug to treat AD...

..All subscales except basic ADL were correlated to burnout. However, regression analysis showed the nursing home hassles to be the most important stresses explaining variance in burnout among family caregivers...

..The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized...

..We aimed to disentangle the effect of chronic multimorbidity and disability on 3-year functional decline and survival in the elderly...

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..The results support the hypothesis that high dose autoantigen immunization induces extensive determinant spreading and chronic course of autoimmune diseases...

..People with low education have unhealthier lifestyles and more cardiovascular risk factors, but it is unclear how this affects the association between education and dementia...

..Here we provide additional evidence that exploratory activity is influenced by BDNF...

..Multimorbidity is the most common clinical picture of the elderly and may be increased by unhealthy behaviors linked to education...

..To describe the association between late-life body mass index (BMI) and dementia development with a time perspective and to investigate the effect of weight changes on dementia incidence...

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..Thus, in addition to the biochemical data, there is now genetic evidence of association between COL25A1 and risk for Alzheimer's disease...

..Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living...

..To investigate whether cerebrovascular disease (CVD) and apolipoprotein E (APOE) epsilon4 allele were associated with cognitive decline and whether the relationship between CVD and cognitive decline varied by APOE epsilon4 status...

..Our objective was to define clinically meaningful outcomes in donepezil versus placebo treatment in severe Alzheimer's disease (AD) and to describe characteristics of responders...

..RT-PCR showed the expression of MCR1, MCR3, MCR4 and MCR5 mRNA. The combined data suggest that the effect of alpha-MSH in increasing IL-6 release from the human microglial cell line is mediated by MCR3 or MCR5...

..Alzheimer's disease (AD) is a devastating illness that causes enormous emotional stress to affected families and is associated with substantial medical and nonmedical costs...

..Additionally, IL-18 participates in fundamental inflammatory processes that increase during aging. In the present study, we were interested in the role of IL-18 in KA-induced neurodegeneration in aged female C57BL/6 mice...

..The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated...

..The final phosphorylation state of tau is possibly caused by the synergic action of the three enzymes...

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