HONOLULU HEART PROGRAM:STUDY OF STROKE AND DEMENTIA

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The long-term goal of this investigation is the development of more effective methods for preventing and treating stroke and dementia related to cerebrovascular disease. The study will be based on data including risk factors and autopsy brain sections from deceased men from the Honolulu Heart Program. In this cohort medial and intimal lesions of brain parenchymal arteries are significantly associated with brain infarction and 3 times more common men dying of stroke than of non- cardiovascular causes. The specific aims of the study are: 1) Delineation of the morphologic characteristics of the brain parenchymal artery lesions, their regional anatomic distribution, and their relationship to changes in adjacent brain parenchyma and the degree of atherosclerosis in the major intracranial arteries; 2) Characterization of the relationship in men between the arterial lesions and advancing age; 3) Characterization in men over 60-65 years of age of the relationship of the arterial lesions to stroke, brain infarction or hemorrhage, and dementia; 4) Identification of additional risk factors associated with the arterial lesions. The arterial lesions and adjacent brain parenchyma will be examined with conventional histologic stains and immunohistochemical markers for specific cellular and extracellular components of the arterial wall. The prevalence and extent of each type of arterial lesion will be determined at 3 anatomic sites. Baseline risk factors thought to be related to stroke and brain infarction will be examined for association with the arterial lesions. Statistical tests of association will be based on univariate and multivariate linear and logistic regression models controlled when necessary for age. The study will clarify the relationship of the arterial lesions to aging, define the influence of the arterial changes on the development of stroke, brain infarction, and dementia, and provide a better understanding of vascular dementia. Morphologic delineation of the arterial lesions will assist the use of experimental models to study molecular mechanisms underlying the lesions and the development of pharmacologic methods for controlling these mechanisms. Further examination of risk factors for the arterial lesions will indicate opportunities for prevention or modifying their evolution.