Premature Cardiovascular Disease and Brain Health in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

AbstractBackgroundCardiovascular disease (CVD) is associated with cognitive impairment and dementia risk in late life, yet little is known about the role of premature (defined younger than 60 years) CVD events with cognition and brain health earlier in the life course, including in midlife. As part of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, we investigated the association of premature CVD events in young and middle adulthood with cognition and white‐matter health in midlife.MethodsWe studied 3,146 Black and White participants (57% women, 48% Black) aged 18‐30 years at baseline (1985‐86) who were followed up to Year 30 (mean age 55.1±3.6 years) when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI with measures of white matter hyperintensity (WMH) burden and white matter integrity. Premature CVD events were adjudicated based on participants' history and medical records of coronary heart disease, stroke/TIA, cardiac revascularization, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the association of premature CVD with cognitive and structural brain measures.ResultsFive percent (n = 147) of participants had premature CVD events over the 30 years. Having premature CVD events was associated with lower cognitive function in all domains. After adjustment for demographics, education, depressive symptoms, physical activity, diet, APOE ε4, and cardiovascular risk factors (CVRFs), premature CVD was associated with lower cognition (z‐standardized) except for verbal fluency: global cognition (‐0.19, 95% CI ‐0.35 to ‐0.03), verbal memory (‐0.24, 95% CI ‐0.41 to ‐0.07), processing speed (‐0.46, 95% CI ‐0.63 to ‐0.30), and executive function (‐0.38, 95% CI ‐0.56 to ‐0.20). Premature CVD was also associated with greater WMH volumes (total, frontal, temporal, and parietal lobes) and alternations of white matter integrity (higher total and temporal lobe mean diffusivity and lower parietal lobe fractional anisotropy) after adjusting for demographics, total intracranial volume, and CVRFs.ConclusionPremature CVD is associated with worse midlife cognition and white‐matter health independent of CVRFs. Young and middle adulthood is a critical time for CVD prevention, the efforts of which may delay the onset of cognitive decline and dementia later in life.