The long term goals of this proposal are to investigate the antecedents of successful aging, age-related cognitive decline, and dementia in a unique population of 2283 participants in the Baltimore Longitudinal Study of Aging (BLSA/NIA), a 36 year prospective study of aging. Studies of risk factors for Alzheimer's disease (AD) in this cohort will be extended to include antecedents for additional outcomes: a) rate of memory loss with aging (age-related memory decline, defined with longitudinal observations from the BLSA database, and stable cognitive performance with age); b) successful aging (longevity greater than 90 years, Active Life Expectancy ALE); c) dementia, particularly AD. By examining psychological differences, detected in AD patients 10-20 years before dementia, Specific Aim 1 is designed to test the hypothesis that subjects with higher cognitive performance (visual memory and vocabulary) in midlife, will have greater longevity and ALE.
Aim 2 will investigate family history and genetic markers, initially for ApoE alleles in promoting or preventing cognitive decline. Antecedent physiological measures (including glucose tolerance, insulin secretion, pulmonary and cardiac function, and lipid profiles) will be determined for each outcome in Aim 3, and antecedent medical history variables are examined in Aim 4. A nonconcurrent prospective design is imposed on the BLSA. Subjects are traced to the present to determine outcomes in all Active, Inactive, and Deceased participants by direct examination (including home visits), medical records, and collateral informant interviews. Cross-sectional and longitudinal analytic strategies are used to examine prospective data up to 36 years before outcome. The BLSA provides a unique database to study the precursors of cognitive aging and longevity. Based on the concept that the processes of aging are lifelong, our studies will provide extraordinarily valuable information for understanding the biological expression of aging in health and disease.
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