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To examine the prospective associations between total cholesterol (TC) variability and cognitive function in a large sample of Chinese participants aged 45 years and above. A total of 6,377 people who participated in the China Health and Retirement Longitudinal Study (CHARLS) were included. TC variability was defined as the intra-individual standard deviation over two blood tests in CHARLS 2011 and 2015 (Wave 1 and Wave 3). Cognitive function was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status (TICS). Multivariate linear regression models (MRLMs) and generalized estimating equation (GEE) were used to investigate associations between TC variability and cognitive scores. After adjusting for potential confounders, male participants with higher visit-to-visit TC variability showed lower global cognition scores ( β  = − 0.71,  P  < 0.001). After further adjustment for baseline cognition, the association remained statistically significant ( β  = − 0.68,  P  < 0.001). The domains with declines were focused on episodic memory ( β  = − 0.22,  P  = 0.026) and TICS ( β  = − 0.44,  P  = 0.004). However, these associations were not found in women ( β  = − 0.10,  P  = 0.623). For men, the rates of decline in global cognition increased by 0.14 ( β  = − 0.14,  P  = 0.009) units per year while TC variability increased by 1 mmol/L. For males, higher visit-to-visit TC variability correlated with lower cognitive function and an increased rate of decreases in memory. More attention should be paid to cognitive decline in males with high TC variability, and particularly, on decreases in memory, calculation, attention and orientation.

Higher visit-to-visit total cholesterol variability is associated with lower cognitive function among middle-aged and elderly Chinese men