Cerebrovascular Contributions to Brain Aging and Dementia

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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.