ApoB, Small-dense LDL-C, Lp(a), LpPLA Activity, and Cognitive Change

Objective: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change.

Methods: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A (LpPLA) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status.

Results: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global scores with every 10-mg/dL higher sdLDL-C level (Δ DSST score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST score, -0.092; -0.0164, -0.019 and Δ global score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global score (-0.10) was comparable with that of having 1 ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global scores. LpPLA activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users.

Conclusions: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.