The existing resource of longitudinal data from the NHLBI Twin Study, the relatively large sample size, the use of comprehensive and state-of-the-art measures of brain function and structure will provide us with an unprecedented opportunity to examine previously unexplored associations between CVD risk factors and indices of brain aging in older twins. 1. Conduct a fourth exam in an estimated 641 individuals including, 120 monozygotic (MZ) and 120 dizygotic (DZ) intact pairs, that will repeat a core battery of assessments given in previous examinations and add new neuropsychological tests and cerebral NM scanning. 2. Evaluate the prospective and cross-sectional relationships of cardiovascular risk factors collected over 23 to 25 years of follow-up (e.g., blood pressure, lipids, obesity, smoking) and MRI indices of brain morphology assessed at the fourth exam. 3. Determine the extent that twins discordant for essential hypertension or non-insulin dependent diabetes mellitus (NIDDM) or cardiovascular disease (CVD) show different MRI profiles. 4. 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. 5. Use the data from exams I to 3 to investigate prospective relationships between CVD risk factors and decline in cognitive performance from Exam 3 to Exam 4. 6. Determine the heritability of the new measurements obtained for the first time at the fourth examination cycle [e.g., MRI measures of white matter hyperintensities (WMHIs), infarct area and location, and ventricular volumes]. 7. Conduct multivariate genetic analyses to determine the contribution of genes and the environment to the covariation among physical, physiological, and neuropsychological variables.
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