ABSTRACT: BACKGROUND:Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer's disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment, MCI). OBJECTIVE:Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. METHODS:3,117 MCI (74 ± 8 years, 56% female) and 6,603 NC participants (72 ± 8 years, 68% female) were drawn from the National Alzheimer's Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, gender, race, education, and follow-up time (in longitudinal models). RESULTS:In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values <0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values <0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p = 0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. CONCLUSIONS:An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation.
