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P3‐174: D‐ribosylated tau forms globular aggregates with high cytotoxicity
Author(s) -
Wei Yan,
Chen Lan,
He RongQiao
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.1048
Subject(s) - glycation , thioflavin , chemistry , alexa fluor , blot , tau protein , cytotoxicity , microbiology and biotechnology , amyloid (mycology) , biophysics , ribose , fluorescence , biochemistry , alzheimer's disease , biology , enzyme , in vitro , receptor , physics , medicine , inorganic chemistry , disease , pathology , quantum mechanics , gene
Background: There is increasing evidence that vascular factors such as hypertension play a role in Alzheimer’s pathology. However, evidence for the benefit of antihypertensive treatment in dementia prevention is inconclusive. This is mainly due to the limitations of previous studies where dementia and cognitive decline were secondary to cardiovascular outcomes in hypertension treatment trials. Here we discuss the factors for consideration in designing a trial for the primary prevention of dementia and cognitive decline, based on experience of two cognitive substudies of major antihypertensive trials. Methods: The Study on COgnition and Prognosis in the Elderly (SCOPE) was a prospective, double-blind, randomized, parallel group study to assess the benefits of the angiotensin-receptor-blocker candesartan at reducing the risk of major cardiovascular events. We conducted a detailed cognitive substudy using the Cognitive Drug Research computerised assessment system and measures of executive function at the largest recruiting centre (n1⁄4257). The assessment and analysis methodology developed in the SCOPE substudy was later implemented in PRoFESS-COG, a cognitive substudy (n1⁄4566) of the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS) trial, conducted at 43 sites in 9 countries, using 8 languages. Results: Experience of conducting cognitive substudies of two antihypertensive trials has identified a number of issues for consideration in the design of a future primary prevention study, including: selection of target population; duration of study; treatment regime/ use of placebo; target blood pressure; selection of primary and secondary outcomes; differential length of follow-up and rolling recruitment; avoiding ‘sick-quitters’; benefits of computerised cognitive testing; language availability of tests; assessment of dementia endpoints in different countries; and standardisation across sites. Recommendations on the key issues will be presented. Conclusions: Primary prevention trials of dementia will likely require large studies of lengthy duration where the final design is a compromise between the ideal and the practical. Experience from previous studies shows that it is at least feasible to collect comprehensive and meaningful cognitive data across multiple sites and languages using a standardised, computerised assessment battery.