Cerebrovascular Contributions to Brain Aging and Dementia

描述（由申请人提供）：脑血管对脑老化和痴呆的贡献。脑血管疾病（CVD）以复杂的方式导致许多有害的与年龄相关的疾病，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，在这些情况下，人们对心血管疾病如何影响大脑和认知知之甚少。该提案的目标是通过使用一系列新颖、先进的神经成像程序来定义CVD的认知和神经后果，以及CVD相关变化如何改变AD临床衰退的过程。目的1。确定CVD对老年人和AD患者脑灰质（GM）和白质（WM）变性的影响。假设1。脑血管健康不良导致额叶GM和WM变性。基线时的高卒中风险预示着后续随访评估时的组织退化。目标2。确定心血管疾病相关的大脑变化如何导致认知能力下降。假设2。心血管疾病与认知能力下降之间存在联系，中风风险与工作记忆之间存在强烈关联，而不是长期记忆。目标3。了解CVD对临床状态、脑老化和AD进展的影响。假设3。心血管疾病与认知能力的变化有关，中风风险与工作能力下降之间的关系最为明显，而不是长期记忆能力。心血管疾病相关的WM变性是发展为痴呆的风险。心血管疾病风险将使用Framingham卒中风险概况来描述，该概况整合了临床和定量生理数据。我们将模拟CVD测量和MRI测量之间的关联，重点关注中风风险如何预测随后的神经变性和临床衰退。CVD的测量将与认知能力的变化和成像测量相关，这些测试间隔2年和4年，以确定CVD或相关的大脑变化是否会影响从轻度认知障碍到痴呆的转换率。从所提出的研究中获得的知识将有助于AD和CVD相关脑变性的鉴别治疗干预。

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.