Non-linear associations of serum lipid levels with cognitive decline: Findings from the ELSA-Brasil cohort.

Background And Aims: Elevated low-density lipoprotein-cholesterol (LDL-C) is a modifiable risk factor for dementia, but evidence on other lipids is inconsistent, particularly in studies from low and middle-income countries. This study aimed to assess the association between lipid levels and cognitive decline in the ELSA-Brasil cohort.

Methods: In this prospective study, baseline serum lipid profile [total cholesterol (TC), LDL-C, high-density lipoprotein-cholesterol (HDL-C), triglycerides, and non-high-density lipoprotein-cholesterol (Non-HDL-C)] was analyzed. Cognition was assessed in three waves four years apart using the CERAD Word List, the semantic and phonemic verbal fluency, Trail Making Test B (TMT-B), and a global score.

Results: ln 12,870 individuals at baseline, the mean (SD) age was 51.4 (8.9) years old, 55.4 % were women, and 53.4 % White. Over eight years of follow-up, inverted U-shape associations of TC with memory [Effective Degrees of Freedom (EDF) = 2.975; P = 0.006] and global cognitive decline (EDF = 2.957; P = 0.014), LDL-C with memory (EDF = 2.976; P = 0.021), verbal fluency (EDF = 2.973; P = 0.041), and global cognitive decline (EDF = 2.962; P = 0.030), and Non-HDL-C with memory (EDF = 2.975; P = 0.012) and global cognitive decline (EDF = 2.963; P = 0.035) were observed. A cubic-shaped association with TMT-B (EDF = 2.981; P = 0.005) was observed for HDL-C. Inverted U-shape associations of TC (EDF = 2.946; P < 0.001), LDL-C (EDF = 2.956; P = 0.007), and Non-HDL-C (EDF = 2.951; P = 0.006) in participants aged less than 60 years and inverted U-shape associations of TC (EDF = 2.882; P = 0.044) in women were observed for global cognitive decline.

Conclusions: Non-linear associations of baseline serum lipids with a decline in different cognitive domains over eight years of follow-up were observed, particularly in individuals younger than 60 years and in women.