AMYLOID PATHOLOGY AND COGNITION IN NORMAL ELDERLY

描述（由申请人提供）：淀粉样蛋白- β (Abeta)蛋白在大脑中的沉积被认为是阿尔茨海默病（AD）的原因。然而，在死前没有临床阿尔茨海默病的人的大脑中发现了死后淀粉样斑块沉积，这一发现得到了不同的解释，支持和反驳了这一假设。这种广泛的解释部分是由于缺乏对没有表现出痴呆临床症状的人的淀粉样蛋白沉积自然史的体内纵向数据。该提案将评估不符合轻度认知障碍（MCI）或AD临床标准的“正常”老年受试者脑淀粉样蛋白沉积的体内证据。我们称这些受试者为“临床未受损”。我们将解决三个基本问题：1)淀粉样蛋白沉积在临床未受损的老年人中有多普遍；2)临床未受损老年人（与年轻人相比）认知表现的较大变异性是否可以用淀粉样蛋白沉积的存在或不存在来解释？ 3)有淀粉样蛋白沉积证据的临床未受损老年人是否一定会发展为MCI或AD的临床诊断？

DESCRIPTION (provided by applicant): Deposition of amyloid-beta (Abeta) protein in the brain has been postulated to be the cause of Alzheimer's disease (AD). However, the finding of post-mortem amyloid plaque deposition in the brains of individuals in whom the absence of clinical AD was well-documented prior to their death has been variably interpreted to both support and refute this hypothesis. This wide range of interpretations is partly due to the lack of in vivo longitudinal data on the natural history of amyloid deposition in persons who do not show clinical symptoms of dementia. This proposal will assess in vivo evidence of brain amyloid deposition in "normal" elderly subjects who do not meet clinical criteria for mild cognitive impairment (MCI) or AD. We refer to these subjects as "clinically unimpaired". We will address three fundamental questions: 1) How common is amyloid deposition in clinically unimpaired elderly; 2) Is the greater variability of cognitive performance in the clinically unimpaired elderly (compared to the young) explained by the presence or absence of amyloid deposition and 3) Will clinically unimpaired elderly who have evidence of amyloid deposition invariably progress to a clinical diagnosis of MCI or AD? Our group has developed an in vivo amyloid imaging positron emission tomography (PET) radiotracer termed "Pittsburgh Compound-B" (PIB). We propose to use this new amyloid imaging technology to provide insight into the questions raised above. The proposed research will test the central hypotheses that amyloid deposition can be demonstrated in clinically unimpaired elderly, that amyloid deposition will correlate with common cognitive changes of "normal aging" and both amyloid deposition and sub-clinical cognitive deficits will progress in tandem over time. With extended periods of observation that will begin in, but extend beyond this study, we hypothesize that this progression will lead to clinical AD. Subjects in their 60's, 70's and 80's will be screened to rule-out dementia using a standard "diagnostic neuropsychological assessment". Clinically unimpaired subjects will be further tested, using well-established cognitive measures, to determine the presence of sub-clinical decrements in cognitive performance commonly found in "normal aging". All subjects will receive PET imaging with PIB and FDG (the latter being the current standard for functional neuroimaging in AD). All assessments will be performed at baseline and 24 months. We will complete 24 month follow-up on 15 65-69 y/o, 25 75-79 y/o and 25 80-84 y/o subjects. Subjects identified as amyloid-positive at 24 months will be followed yearly in years four and five.