Cerebrovascular Contributions to Brain Aging and Dementia

描述(申请人提供)：脑血管对脑老化和痴呆症的贡献。脑血管疾病(CVD)以一种复杂的方式导致了一系列与年龄相关的有害疾病，包括认知能力下降、神经退行性变和阿尔茨海默病(AD)的临床综合征。然而，关于心血管疾病在这些情况下如何影响大脑和认知，人们知之甚少。这项建议的目标是定义CVD的认知和神经后果，以及CVD相关的变化如何通过使用一系列新的、先进的神经成像程序改变AD的临床下降过程。目的1.探讨脑血管病变在老年人和AD患者脑灰质和白质变性中的作用。假设1.脑血管健康状况不佳导致额叶GM和WM变性。基线的高卒中风险预示着后续的组织退变。目的2.确定脑血管病相关的脑变化如何导致认知功能下降。假设2：心血管疾病和认知能力下降之间存在联系，而中风风险和工作记忆之间存在很强的联系，而不是长期记忆。目的3.了解心血管疾病是如何影响临床状态、脑老化和进展为AD的。假设3.心血管疾病与认知随时间的变化有关，中风风险与工作能力下降之间的关系最为显著，而不是长期记忆能力。脑血管病相关的白质变性是痴呆发生的危险因素。心血管疾病风险将使用整合了临床和定量生理数据的弗雷明翰卒中风险概况来表征。我们将对CVD测量和MRI测量之间的关联进行建模，重点关注中风风险如何预测随后的神经变性和临床衰退。心血管疾病的测量将与认知能力的变化和相隔两年和四年的测试期间的成像测量有关，以确定心血管疾病或相关的大脑变化是否影响从轻度认知障碍到痴呆症的转化率。这些研究将有助于AD和CVD相关性脑变性的区别治疗干预。

DESCRIPTION (provided by applicant): Cerebrovascular contributions to brain aging and dementia. Cerebrovascular disease (CVD) contributes in a complex manner to a host of detrimental age-related conditions including cognitive decline, neurodegeneration, and the clinical syndrome of Alzheimer's disease (AD). Still, little is known about how CVD affects the brain and cognition in these conditions. The goal of this proposal is to define the cognitive and neural consequences of CVD, and how CVD-related changes alter the course of clinical decline in AD through the use of a host of novel, advanced neuroimaging procedures. Aim 1. To identify the contribution of CVD to brain gray (GM) and white matter (WM) degeneration in older adults and in patients with AD. Hypothesis 1. Poor Cerebrovascular health contributes to GM and WM degeneration in the frontal lobe. High stroke risk at baseline predicts subsequent tissue degeneration at follow up assessment. Aim 2. To determine how CVD associated brain changes contribute to cognitive decline. Hypothesis 2. A relation exists between CVD and cognitive decline with strong associations between stroke risk and working memory, as opposed to long term memory. Aim 3. To understand how CVD contributes to clinical status, brain aging, and the progression to AD. Hypothesis 3. CVD is related to changes in cognition across time with most pronounced relations between stroke risk and reduced working, as opposed to long term, memory abilities. CVD related WM degeneration is a risk for the development of dementia. CVD risk will be characterized using the Framingham Stroke Risk profile which integrates clinical and quantitative physiological data. We will model the association between CVD measures and MRI measures of with a focus on how stroke risk predicts subsequent neural degeneration and clinical decline. Measures of CVD will be related to change in cognitive abilities and imaging measures across testing sessions separated by two and four years to determine whether CVD or associated brain changes affect the rate of the conversion from mild cognitive impairment to dementia. Knowledge from the proposed studies would be useful in the differential therapeutic intervention of AD and CVD related brain degeneration.