Insular AD Pathology and Autonomic Function

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DESCRIPTION (provided by applicant): The dementia of Alzheimer's disease (AD) represents the final stages of a pathological process that spans decades. Before clinicians can detect dementia, AD pathology may already have reached the insular cortex, which is related to cardiovascular autonomic control. Right insular lesions are associated with bradyarrhythmias and increased mortality. Autopsy studies suggest that 40% of octogenarians may be at risk for insular AD pathology. Similarly, 20-40% of healthy octogenarians have unexplained "age related" supaventricular arrhythmias on 24-hour Holter records. Visuospatial cognitive measures are associated with mortality in AD. We have observed a robust association between similar tests and mortality in non-demented elderly retirees. Thus, we suspect that preclinical AD may be responsible for "age-related" autonomic dysfunction and "cardiovascular" /fall related morbidity and mortality in nondemented elderly persons. This study will examine the specific independent associations between insular AD and non-AD pathology at autopsy and antemortem longitudinal change in cardiovascular autonomic function among participants in the Honolulu-Asia Aging Study (HAAS). HAAS is a longitudinal study of heart disease and stroke among 8006 Japanese-American men. HAAS involves cardiovascular exams from 1965, '67, '71, '91, '94, '97, '99, '01 plus serial cognitive exams since '91 and ongoing surveillance. 600 autopsies have been performed (approximately 20% of recent decedents). The majority have full clinical data on file. N = 1523 subjects remain in the active HAAS cohort, providing the potential for future prospective studies of the associations we demonstrate in this proposal. A significant effect of insular AD pathology on autonomic control in either demented or non-demented persons at risk for AD would have important implications. Autonomic dysfunction could provide a sensitive indicator of future AD dementia conversion risk, while interventions against supraventricular bradyarrhythmias may decrease mortality in the earlier stages of AD.