LAUSR

It is unclear how coronary heart disease (CHD) risk across the adult lifespan affects latelife cognition. We estimated associations of mid-life and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 or 70 years) in N=2,892 Framingham Offspring Study participants who completed CHD risk assessments approximately every four years since 1971 and underwent neuropsychological testing between 1999-2014. We stratified analyses by apolipoprotein (APOE)-ε4 status. Using linear mixed effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance at 70 years (β=-0.560 standard deviation (SD) units, 95% Confidence Interval, [CI]: -0.874, -0.246), executive function (β=-0.624 SD units, 95% CI: -0.916, -0.332), and memory (β=-0.560 SD units, 95% CI: -0.907, -0.213), but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations of duration of elevated CHD risk during midlife with levels but not trajectories of later-life cognitive outcomes. Associations were not modified by APOE-ɛ4. Mid-life elevated CHD risk is associated with lower cognition, independent of APOE-e4, suggesting risk of vascular disease may not contribute a second hit to AD.