Journal of Alzheimer's disease : JAD
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Longitudinal changes of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have been studied, but there are few consistent conclusions and even less is known about their variation during the different stages of the disease. We hypothesized that changes in CSF biomarker values would correlate with the progression of the cognitive decline in AD. One hundred and thirty-one memory clinic patients [56 AD, 57 mild cognitive impairment (MCI), 10 other neurological disorders, eight unimpaired subjects] underwent a clinical follow-up with repeated Mini-Mental Status Examination (MMSE) tests and two lumbar punctures with a median interval of 3 years. ⋯ Concentrations of hyperphosphorylated tau decline in the late stages of the AD process. The decrease of p-tau-181 appears to correlate with cognitive functioning and probably reflects neuronal loss. More longitudinal studies of CSF biomarker dynamics are needed, especially in patients during the preclinical stage of the disease.
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To evaluate the mortality, thirteen years after the baseline wave (1994), of participants suffering dementia in the Neurological Disorders in Central Spain (NEDICES) Cohort Study, we conducted a population-based cohort study in the elderly (65 years and more) with 5,278 screened participants at baseline. Mortality has been evaluated by means of the National Death Registry of Spain at 1-5-2007, 13 years after enrolment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to dementia severity and type, adjusting for potential covariates (gender, age, level of education, and co-morbidity). ⋯ Dementia intensity increases the mortality risk at ten years in the NEDICES Study as in other cohort studies. Age, gender, and co-morbidity are associated with higher mortality in dementia patients. Almost one third of deaths in persons over 85 years-old could be attributable to dementia.
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Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Prion disease, Huntington's disease, and amyotrophic lateral sclerosis are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation in selected brain regions. The aggregates usually consist of insoluble fibrillar aggregates containing misfolded protein with β-sheet conformation. The most probable explanation is that inclusions and the aggregates symbolize an end stage of a molecular cascade of several events, and that earlier event in the cascade may be more directly tied up to pathogenesis than the inclusions themselves. ⋯ Compelling evidence suggests the role of misfolded proteins in the form of oligomers might lead to synaptic dysfunction, neuronal apoptosis and brain damage. However, the mechanism by which oligomers trigger neurodegeneration still remains mysterious. The aim of this article is to review the literature around the molecular mechanism and role of oligomers in neurodegeneration and leading approaches toward rational therapeutics.
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Dementia has a significant impact on the health and social care systems of the European Union (EU), on patients, on family and friends who provide unpaid care, and on the wider economy and society. Information about its economic burden will be helpful when deciding the allocation of future research funds. We included the 15 countries who were members of the EU (EU-15) before the Eastern enlargement in 2004. ⋯ In conclusion, dementia poses a significant economic burden to European health and social care systems, and society overall. Our results will be helpful for policy makers in evaluating policy impact and prioritising research expenditures. This study also highlights the need for more accurate and comparable dementia-related data across the European countries.
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Alzheimer's disease (AD) is a progressive neurodegenerative disease involving the decline of memory and other cognitive functions. Mild cognitive impairment (MCI) represents a transition phase between normal aging and early AD. The degeneration patterns of the white matter across the brain in AD and MCI remain largely unclear. ⋯ Similar white matter regions with reduced anisotropy were also found in MCI patients but with a much less extent than in AD. Between the AD and MCI groups, there were significant differences in the axial and mean diffusivities of the white matter tracts adjacent to the posterior cingulate cortex/precuneus without anisotropy changes. Taken together, our findings based upon multiple diffusion indices (FA, axial, radial and mean diffusivities) suggest distinct degeneration behaviors of the white matter in AD and MCI.