The NHLBI Twin Study is a longitudinal study of cardiovascular disease (CVD) in 514 pairs of male twins, 254 monozygotic (MZ) and 260 dizygotic (DZ), born in 1917-1927 and 42 to 56 years old when first examined in 1969-73. Two follow-up examinations, conducted in 1980-81 and in 1986-87, assessed CVD status and collected repeat measurements of physiological, biochemical, and psychosocial risk factors. In the most recent follow-up (1986-87), we obtained baseline data on cognitive performance in 622 individuals, including 132 MZ and 134 DZ twin pairs. We are proposing to conduct a fourth exam in the surviving subjects of this cohort that will utilize this rich resource of available data to determine the relationship between cardiovascular risk factors collected over 23 years of follow-up, changes in cognitive function since the last exam, and brain morphology assessed by magnetic resonance imaging (MRI). Given the current mean age of this cohort (72 years), the next several years represent a critical time to monitor age related changes in brain morphology and cognition. The addition of a fourth exam will make the NHLBI Twin Study the longest longitudinal study of cardiovascular disease epidemiology in twin subjects (23 to 25 years of follow-up) and the first to investigate the contribution of genes and the environment to associations between CVD risk factors, cognitive performance, and brain morphology. Specific objectives of this study are: (1) Evaluate the prospective and cross-sectional relationships of cardiovascular risk factors collected over 23 years of follow-up (e.g., blood pressure, lipids, obesity, smoking) and indices of brain morphology assessed at the fourth exam; (2) Determine the extent that twins discordant for essential hypertension or non-insulin-dependent diabetes mellitus (NIDDM) or cardiovascular disease (CHD) show different MRI profiles; (3) Characterize the neuropsychological changes in performance from Exam 3 to Exam 4 and determine the contribution of genes and the environment to stability or change; (4) Use the data from exams 1 to 3 to investigate prospective relationships between CVD risk factors and decline in cognitive performance from Exam 3 to Exam 4; and (5) Determine the heritability of the new measurements obtained for the first time at the fourth examination cycle (e.g., MRI measures of infarct area and localization, white matter hyperintensities (WMHI), and ventricular volumes). The existing longitudinal data from the NHLBI Twin Study, the relatively large sample size, the use of state-of-the-art measures of brain function and structure, and the expertise of the investigators in the analyses of twin data will provide us with an unprecedented opportunity to examine previously unexplored associations between CVD risk factors and indices of brain aging in older twins.
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