Brain Imaging and Cognitive Predictors of Stroke and Alzheimer Disease in the Framingham Heart Study

Background and Purpose— Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk. Methods— A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, >55 years; mean, 65.7±7.0) between 1999 and 2004; participants were also free of other neurological conditions that could affect cognition and >90% also had brain MRI examination. We related cognitive and MRI measures to risks of incident stroke and AD ≤10 years of follow-up. As a secondary analysis, we explored these associations in The Framingham Heart Study original cohort (mean age, 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination, respectively). Results— A total of 55 Offspring participants sustained strokes and 31 developed AD. Offspring who scored <1.5 SD below predicted mean scores, for age and education, on an executive function test, had a higher risk of future stroke (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.06–4.85) and AD (HR, 3.60; 95% CI, 1.52–8.52); additional cognitive tests also predicted AD. Participants with low (<20 percentile) total brain volume and high (>20 percentile) white matter hyperintensity volume had a higher risk of stroke (HR, 1.97; 95% CI, 1.03–3.77 and HR, 2.74; 95% CI, 1.51–5.00, respectively) but not AD. Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts (HR, 4.41; 95% CI, 2.00–9.72 and HR, 2.37; 95% CI, 1.12–5.00, respectively). A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers. Conclusions— Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction.