Anatomical studies suggest that the brain microvasculature is abnormal in patients with Alzheimer's disease. Three general abnormalities have been described. First, cerebral amyloid angiopathy (CAA), characterized by the presence of amyloid within brain capillary and arteriolar walls, is a frequent occurrence in patients with Alzheimer's disease. Second, several of """"""""deformities"""""""" of cerebral arterioles and capillaries are described, including thickening of the capillary walls and loop formations. Finally, neurotransmitter systems within brain known to influence the microvasculature, namely the central noradrenergic and cholinergic systems, are severely affected in patients with Alzheimer's disease. Despite the presence of these abnormalities the hypothesis that the function of the cerebral vasculature is impaired in Alzheimer's disease has not been systematically evaluated. We propose to test that hypothesis by examining microvascular function using positron emission tomography (PET) to study: 1) resting state measurements of regional blood flow, vascular permeability-surface area product and metabolism; 2) the response of the vasculature to functional activation (e.g., visual or somatosensory stimulation); and (3) the relationship of functionally-induced vascular changes to changes in local glucose utilization. We will study 50 healthy elderly and 50 subjects with senile dementia of the Alzheimer type (SDAT) and compare their data to those of healthy young adults. The prospect of autopsy confirmation of vascular pathology is an added strength. Although PET is ideally suited to explore these issues it has been plagued by the problem of partial volume averaging due to brain atrophy. As a major component of this project we propose to develop and implement two new, innovative strategies of data analysis. The first is designed to correct PET regionally for the presence of atrophy using magnetic resonance imaging (MRI). The second performs image wide comparisons of PET data between subject groups after transforming all PET data to a common anatomical coordinate system using MRI information.
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