Abstract
Studies on the trajectories of lipid profile with cognitive decline are scarce and inconsistent. We examined this association and explored potential effect modification. Lipid profiles including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol (TC) were measured at baseline, first and second follow-ups, and classified into trajectory groups. Immediate, delayed memory recall and cognitive function were assessed by the immediate (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups, and converted into standardized scores. Linear mixed-effect model was used. Results show that elevated HDL-C was associated with increasing annual change rates in DWRT and MMSE scores (β (95% confidence intervals) = 0.005 (-0.001 to 0.011) SD/year and 0.020 (0.014 to 0.027) SD/year, respectively), while LDL-C and TC were associated with a decrease in DWRT scores (-0.005 (-0.008 to -0.001) SD/year and - 0.009 (-0.011 to -0.006) SD/year, respectively). Moderate-increasing HDL-C, high-decreasing LDL-C or moderate-decreasing TC trajectories were associated with increases in DWRT, IWRT and MMSE scores. Stronger associations were identified for HDL-C with an increase in MMSE scores within the lower family income group and for LDL-C with a decrease in IWRT scores among individuals taking lipid-lowering drug. In conclusion, HDL-C was associated with improvements, while LDL-C and TC with decline in memory and cognitive function. Increasing HDL-C and decreasing LDL-C and TC trajectories predicted better memory and cognitive performance. The observed effect modifications highlight the importance of personalized approaches in lipid management to optimize cognitive outcomes.