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

Abstract

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 β (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 (β=-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 (β=-0.019 SD/year [95% CI, -0.031 to -0.007]) but not in the lipid-lowering drug group (β=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.