Gender-specific association between unidirectional variation of cholesterol and cognitive decline: a longitudinal study of middle-aged and elderly adults

Abstract

Background Higher fluctuation of cholesterol has been shown associated with cognitive decline. But the association between unidirectional variation of cholesterol and cognition remains unclear. In the present study, we examined the association between variation of cholesterol from normal to high level or from high to normal level and cognition. Methods A total of 4,915 participants (mean age, 57.7 years; 49.2% female) with normal cognition in baseline (2011) from the China Health and Retirement Longitudinal Study (CHARLS) were included. Plasma total cholesterol (TC), non-high-density lipoprotein cholesterol (NHDL-C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were divided into two clusters according to cutoff in 2011 and 2015, respectively. Participants were divided into four groups: normal-normal, normal-high, high-normal and high-high. Cognitive functions were assessed by episodic memory and mental intactness. The binary logistic regression was used to analyze the association of cholesterol variation with cognitive decline. Results Participants with increased cholesterol were more likely had lower incidence of cognitive decline. The fluctuations of cholesterol were more likely occurred in females. The odds ratio (OR) and 95% confidence interval (CI) of global cognitive decline in normal-high compared with normal-normal group of TC was 0.61 (0.36–1.03), and significant only in females [OR and 95% CI: 0.50 (0.26–0.97)]; the risk of memory function decline in high-normal group compared with high-high group was increased both in males [OR and 95% CI: 1.98 (1.02–4.05)] and females [OR and 95% CI: 1.61 (1.01–2.74)]. The similarly results were shown in NHDL-C groups [OR and 95% CI of global cognitive decline in normal-high group: 0.50 (0.26–0.95) for overall; 0.38 (0.17–0.85) for females]; but the risk of memory function decline in high-normal group only increased in females [OR and 95% CI: 1.64 (1.02–2.25)]. The risk of mental intactness decline in males significantly decreased in high-normal group of LDL-C compared with high-high group [OR and 95% CI: 0.30 (0.13–0.67)] and increased in high-high compared with normal-normal group [OR and 95% CI: 2.27 (1.18–2.98)]. Conclusions Longitudinal decreasing of TC or NHDL-C is detrimental to cognitive function, especially in females. But LDL-C is still a risk factor of cognitive decline in males.