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Abstract
Background and Objectives To understand the role of premature (defined as ≤ 60 years) cardiovascular disease (CVD) in brain health earlier in life, we examined the associations of premature CVD with midlife cognition and white matter health.
Methods We studied a prospective cohort in the Coronary Artery Risk Development in Young Adults study, who were 18–30 years at baseline (1985–1986) and followed up to 30 years when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI measures of white matter hyperintensity (WMH) and white matter integrity. A premature CVD event was adjudicated based on medical records of coronary heart disease, stroke/TIA, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the associations of nonfatal premature CVD with cognitive performance (z-standardized), cognitive decline, and MRI measures.
Results Among 3,146 participants, the mean age (57% women and 48% Black) was 55.1 ± 3.6 years, with 5% (n = 147) having premature CVD. Adjusting for demographics, education, literacy, income, depressive symptoms, physical activity, diet, and APOE, premature CVD was associated with lower cognition in 4 of 5 domains: global cognition (−0.22, 95% CI −0.37 to −0.08), verbal memory (−0.28, 95% CI −0.44 to −0.12), processing speed (−0.46, 95% CI −0.62 to −0.31), and executive function (−0.38, 95% CI −0.55 to −0.22). Premature CVD was associated with greater WMH (total, temporal, and parietal lobes) and higher white matter mean diffusivity (total and temporal lobes) after adjustment for covariates. These associations remained significant after adjusting for cardiovascular risk factors (CVRFs) and excluding those with stroke/TIA. Premature CVD was also associated with accelerated cognitive decline over 5 years (adjusted OR 3.07, 95% CI 1.65–5.71).
Discussion Premature CVD is associated with worse midlife cognition and white matter health, which is not entirely driven by stroke/TIA and even independent of CVRFs. Preventing CVD in early adulthood may delay the onset of cognitive decline and promote brain health over the life course.
Glossary
- APDQS=
- A Priori Diet Quality Score;
- BMI=
- body mass index;
- CARDIA=
- coronary artery risk development in young adults;
- CHD=
- coronary heart disease;
- CHF=
- congestive heart failure;
- CVD=
- cardiovascular disease;
- CVRF=
- cardiovascular risk factor;
- DSST=
- Digit Symbol Substitution Test;
- DTI=
- diffusion tensor imaging;
- HDL=
- high-density lipoprotein;
- ICV=
- intracranial volume;
- IPW=
- inverse probability weighting;
- PAD=
- peripheral artery disease;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editors were Assistant Editor Andrea Schneider, MD, PhD, and Deputy Editor Brad Worrall, MD, MSc, FAAN.
- Received June 13, 2022.
- Accepted in final form December 2, 2022.
- © 2023 American Academy of Neurology
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