Longitudinal Association of Remnant Cholesterol With Cognitive Decline Varies by Lipid-Lowering Drugs: A Population-Based Cohort Study

Background Although the association between remnant cholesterol (RC) and cognitive impairment has been reported, the association of RC with cognitive decline remains scarce. Also, the role of lipid-lowering therapy in the association is unclear. The study aimed to examine the longitudinal associations of RC with cognitive decline by lipid-lowering drug use during follow-up.Methods and Results The study used data from Wave 2 (2004-2005) to Wave 8 (2016-2017) of the ELSA (English Longitudinal Study of Ageing). Global cognitive functions at baseline (Wave 2) and during the follow-up (Waves 3-8) were assessed by integrating 3 cognitive domains: memory capacity, semantic fluency, and orientation. Multivariate-adjusted linear mixed models were employed to examine the longitudinal associations, with results presented as beta (95% CI) in SD/year. Of the 5053 participants ultimately included, 55.4% were female and the mean age (SD) was 65.7 (9.3) years. Per 1 mmol/L increment in RC was significantly associated with a faster rate of cognitive decline (beta=-0.010 SD/year [95% CI -0.019 to -0.001]). Furthermore, we observed that association pattern between RC and cognitive decline only in the non-lipid-lowering drug group (beta=-0.019 SD/year [95% CI, -0.031 to -0.007]) but not in the lipid-lowering drug group (beta=0.007 SD/year [95% CI, -0.006 to 0.020]), with a significant interaction (P=0.015). Similar findings were observed for the 3 cognitive domains.Conclusions Higher baseline RC levels were associated with steeper cognitive decline. The use of lipid-lowering drugs might mitigate this decline. These findings underscore the importance of early RC monitoring and proactive management with lipid-lowering drugs in clinical practice.