AGE OF DEMENTIA ONSET AND CARDIOVASCULAR RISK FACTORS

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Several ongoing longitudinal studies have found evidence that many cardiovascular disease risk factors (CvRFs) are also risk factors for Alzheimer disease (AD). Most study cohorts, however, do not include many of the oldest old, and when present, they are predominantly female. Data from our center suggest CvRFs may be especially potent for AD in the very old. We selected diabetes, total cholesterol, hypertension, and plasma homocysteine concentration, based on prior research, for primary hypothesis testing. We will investigate whether there is a relationship between each one of these four CvRFs with cognitive decline and AD in an elderly male veteran population and explore whether this effect is strengthened with increased age. An "Aging Research Clinic" will be established at the Bronx VA specifically dedicated to this project. Eligible subjects must be older than 75 (with special emphasis on recruiting the very old) and be free of dementia. In addition to the four primary CvRFs, subjects will receive a comprehensive CvRF examination in conjunction with the cardiovascular research program at the Bronx VA. The four primary risk factors will be directly assessed at baseline in each subject. In addition, the baseline risk factor assessment will include: age, smoking, family history, weight and waistline, prior medical history for cardiovascular events, apolipoprotein E (and other relevant genotyping), C reactive protein, physical activity and other risk factors. Subjects will also be evaluated at baseline for left ventricular hypertrophy, carotid artery intima media thickness and proximal capacitative or large artery compliance, and distal oscillatory small artery compliance by radial artery pulse wave analysis. MRIs will be conducted at baseline in all subjects and at follow up in those who show evidence of cognitive decline (CDR30.5) to assess the role of cerebrovascular disease. The subjects will be followed longitudinally on an annual basis to determine who among them show evidence of cognitive decline (CDR > or = 0.5) and AD, as well as other possible forms of dementias (e.g. vascular dementia). As many of these CvRFs are modifiable, implicating them as risk factors for very late onset cognitive decline and AD holds the potential for making major public health gains for the very old--the fastest growing segment of the U.S. population.