Brain imaging and cognitive predictors of stroke and Alzheimer disease in the Framingham Heart Study

Abstract

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.

Keywords: Alzheimer disease; cognition; magnetic resonance imaging; stroke.

Figure 1

Flow diagram of study participants. A. Original cohort, B. Offspring cohort.

Figure 2

Cumulative incidence of stroke (left) and AD (right) in the Offspring cohort based on age- and gender-adjusted Cox models by number of indicators among: poor performance on Trail making B test, top WMHV quintile and bottom TCBV quintile.