Stroke Risk Profile Predicts Brain Volume and Cognitive Function in Stroke-free Subjects: The Framingham Study
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) and visual memory (e.g. delayed visual reproduction (p<0.01) but not with performance on tests of naming or logical memory (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.