Sporadic cerebral amyloid angiopathy (CAA) is a disorder of the elderly in which A beta deposition in the cortical and leptomeningeal arteries leads to vessel fragility and rupture. The most devastating complication of CAA is lobar intracerebral hemorrhage (ICH), which has a high rate of recurrence. Patients with CAA also have a high prevalence of dementia, partly due to coexisting Alzheimer's disease but also possibly due to brain ischemia. Leukoaraiosis (LA), changes in the cerebral white matter due to chronic ischemia, is known to occur in CAA but the prevalence has never before been investigated. It is unknown whether LA predicts the development of recurrent brain hemorrhage or dementia in CAA patients. Therefore, the following hypotheses will be tested using a prospective cohort design: 1) That LA in CAA patients is associated with an increased risk of pre-ICH dementia, and confers an increased risk of the development of post-ICH dementia, 2) that an increased amount of baseline LA confers an increased risk of recurrent ICH, and 3) that LA progression is associated with the development of dementia and decreased cognitive function. Patients will be recruited from a multi-center NIH-funded clinical trial for the prevention of recurrent lobar ICH, as well as a consecutive database of lobar ICH patients admitted to Massachusetts General Hospital. The amount of LA will be determined at baseline on CT and MRI using modifications of widely used rating scales, and the patients will be followed closely for the outcomes of interest. MRI will be repeated at 8, 16, and 36 months. As part of the Award, the principal investigator will complete formal training in research ethics, biostatistics and epidemiology, and develop further expertise with radiological tools for the investigation of white matter vascular pathology. By completion, he will have obtained the necessary skills to function as an independent investigator with expertise in hemorrhagic cerebrovascular disease and white matter neuroimaging.
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