AMYLOID PATHOLOGY AND COGNITION IN NORMAL ELDERLY

描述（由申请人提供）：淀粉样β（Abeta）蛋白在脑中的沉积被认为是阿尔茨海默病（AD）的原因。然而，发现死后淀粉样蛋白斑块沉积在个人的大脑中，在他们的死亡之前，没有临床AD被充分记录，已经被解释为支持和反驳这一假设。这种广泛的解释部分是由于缺乏体内纵向数据的自然历史的淀粉样蛋白沉积的人谁不显示痴呆症的临床症状。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。我们将这些受试者称为“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上未受损的老年人中有多常见; 2）临床上未受损的老年人（与年轻人相比）认知表现的更大变异性是否可以通过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上未受损的老年人是否总是进展为MCI或AD的临床诊断？ 我们的小组已经开发了一种体内淀粉样蛋白成像正电子发射断层扫描（PET）放射性示踪剂，称为“匹兹堡化合物-B”（PIB）。我们建议使用这种新的淀粉样蛋白成像技术来深入了解上述问题。拟议的研究将测试中心假设，即淀粉样蛋白沉积可以在临床上未受损的老年人中得到证明，淀粉样蛋白沉积将与“正常衰老”的常见认知变化相关，淀粉样蛋白沉积和亚临床认知缺陷将随着时间的推移而同步进展。随着观察期的延长，将开始，但超出本研究，我们假设这种进展将导致临床AD。60多岁、70多岁和80多岁的受试者将接受筛查，以使用标准的“诊断性神经心理评估”排除痴呆症。将使用完善的认知测量对临床未受损受试者进行进一步测试，以确定是否存在“正常衰老”中常见的认知表现亚临床减退。所有受试者将接受PIB和FDG PET成像（后者是AD功能性神经成像的当前标准）。所有评估将在基线和24个月时进行。我们将对15例65-69岁、25例75-79岁和25例80-84岁受试者完成24个月随访。在24个月时被确定为淀粉样蛋白阳性的受试者将在第四年和第五年每年随访一次。

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.