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30 Background: The contribution of stroke risk  factors to the pervasive brain atrophy and cognitive impairment seen  with aging is controversial. This is partly due to a paucity of  longitudinal data in stroke-free subjects. We hypothesize, that even in  subjects who remain free of clinical stroke, exposure to stroke risk  factors may adversely impact brain volume. Objective: To prospectively  examine the association of Framingham Stroke Risk Profile (FSRP) scores  at baseline with MRI brain volume on follow-up, and to further evaluate  the association of brain volume with cognitive function, in a  population-based cohort of stroke- and dementia-free subjects.Methods: Framingham Offspring Study subjects were evaluated  for stroke risk factors at exam 5 (1991–1995). A sex-specific,  composite FSRP score was calculated for each subject, as validated in  prior studies. 909 subjects (age range 42–82, mean age: 61 years, 427  men), who remained free of clinical dementia and stroke, underwent  quantitative MRI imaging and neuropsychological evaluation, 4 to 9  years later (1999–2000). Using linear regression models adjusted for  age and sex, we examined the association between the FSRP score and  Total Cerebral Brain Volume- TCBV (expressed as a ratio of total  cranial volume). We also evaluated the association of TCBV with age-  and education- adjusted scores on a battery of neuropsychological tests  administered at the time of imaging.Results: There was a  strong inverse association between TCBV and the FSRP score (p=0.002).  TCBV also showed a significant positive association with performance on  tests of manual dexterity (e.g. finger tapping; p 0.05).Conclusion: An adverse stroke risk profile predicted lower  MRI brain volume, which in turn was associated with poorer performance  on specific neuropsychological tests suggestive of vascular cognitive  impairment. Pathogenetic mechanisms for these associations in  stroke-free subjects could include various vascular causes for  accelerated brain aging and merit further study.

Stroke Risk Profile Predicts Brain Volume and Cognitive Function in Stroke-free Subjects: The Framingham Study