Associations Between 20-Year Lipid Variability Throughout Young Adulthood and Midlife Cognitive Function and Brain Integrity

Background: Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife.

Method: We studied 3 328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high-density lipoprotein (LDL and HDL) variability as the intraindividual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored.

Results: Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (β = -0.25, 95% CI: -0.42, -0.08), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (β = -0.80, 95% CI: -1.18, -0.41) and brain integrity, for example, smaller total brain volume (β = -0.58, 95% CI: -0.82, -0.34) and worse total brain fractional anisotropy (β = -1.13, 95% CI: -1.87, -0.39).

Conclusions: Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.