Modulators of Cognitive Transition from Normal to MCI

项目总结（见说明）： 该建议旨在研究在AD症状前阶段发生在老年人中的两种最重要的CNS病理（阿尔茨海默病[AD]和血管疾病）之间的关系。我们将专门测试的假设，即淀粉样蛋白沉积的临床影响，在体内检测到的正常人谁进展到轻度认知功能障碍（MCI），后来到AD的大脑是由亚临床血管疾病调制。这项研究的中心假设是，认知正常的受试者与系统性和脑血管疾病将不太可能安装一个代偿反应淀粉样蛋白沉积。患有血管疾病的老年受试者，其中导致AD的神经病理级联反应已经开始，将不太可能维持正常的脑代谢;他们将具有较短的“潜伏期”和更高的MCI发生率。相比之下，血管疾病较少的认知正常受试者将有更多的淀粉样蛋白沉积，因为他们将能够补偿并维持更长的潜伏期。这项纵向研究将检查70名参与银杏记忆评估研究（GEMS）的认知正常受试者的MRI，PET以及脑和全身血管特征。GEMS旨在确定银杏叶与安慰剂相比在降低正常老年受试者和MCI患者全因痴呆和AD发病率方面的有效性。自2001年以来，GEMS对匹兹堡的966名受试者进行了仔细的年度认知评估（平均随访时间：8.5年），该研究于2008年完成。作为将于2010年完成的最后一次检查的一部分，匹兹堡的所有非痴呆参与者被邀请进行脑部MRI和淀粉样蛋白配体（匹兹堡化合物B）PET扫描，大约200名受试者将进入GEMS的最后阶段。从这个人群中，我们将选择70名认知正常的参与者进行本研究; 35名没有淀粉样蛋白沉积，35名有淀粉样蛋白沉积。因此，通过从GEMS中取样，我们将处于独特的地位，研究血管疾病、淀粉样蛋白沉积和正常老年人群认知变化发生之间的关系。

PROJECT SUMMARY (See instructions): This proposal is oriented to examine the relationship between the two most important CNS pathologies that occur in the elderly (Alzheimer's disease [AD] and vascular disease) during the pre-symptomatic phase of AD. We will specifically test the hypothesis that the clinical effects of amyloid deposition detected in vivo in the brain of normal individuals who progress to mild cognitive impairment (MCI) and later to AD is modulated by sub-clinical vascular disease. The central hypothesis of this study is that cognitively normal subjects with systemic and cerebral vascular disease will be less likely to mount a compensatory response to amyloid deposition. Elderly subjects with vascular disease, in whom the neuropathological cascade leading to AD has already started, will be less likely to maintain normal cerebral metabolism; they will have a shorter "latency period", and a greater incidence of MCI. By contrast, cognitively normal subjects with less vascular disease will have more amyloid deposition, since they will be able to compensate and maintain a longer 'latency period." This longitudinal study will examine the MRI, PET, and cerebral and systemic vascular characteristics of 70 cognitively normal subjects participating of the Ginkgo Evaluation of Memory Study (GEMS). The GEMS was conducted to determine effectiveness of ginkgo biloba versus placebo in lowering the incidence of all-cause dementia and AD in normal elderly subjects and those with MCI. The GEMS has conducted careful annual cognitive evaluations since 2001 (mean follow-up: 8.5 years) on 966 subjects in Pittsburgh, and the study was completed in 2008. As part of the last examination to be completed in 2010, all non-demented participants in Pittsburgh were invited to have an MRI of the brain and a PET scan with an amyloid ligand (Pittsburgh Compound B), and approximately 200 subjects will be entered in the last phase of GEMS. From this population, we will select 70 cognitively normal participants for the present study; 35 without and 35 with amyloid deposition. Consequently, by sampling from the GEMS, we will be in the unique position of examining the relationship between vascular disease, amyloid deposition and onset of cognitive changes in a normal elderly population.