Low levels of low-density lipoprotein cholesterol and cognitive decline

The relationship between low levels of serum low-density lipoprotein cholesterol (LDL-C) and subsequent cognitive decline remains conflicting and unclear. The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets (LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events, and less than 70 mg/dL for high risk individuals). Data from wave 13 (2016) to wave 14 (2018) of the Health and Retirement Study (HRS) were utilized. LDL-C concentrations measured at wave 13 were categorized into 5 levels, reflecting currently recommended values for lipid lowering treatment. Of 7129 included participants (mean age: 69.0 ± 9.9 years, 60.3% female), we found that compared to participants with LDL-C levels 70–99.9 mg/dL, those with LDL-C levels < 55 mg/dL had significantly slower 2-year decline rates in global cognitive function (0.244 point/year; 95% confidence interval (CI): 0.065, 0.422, P = 0.008), working memory (0.068 point/year; 95% CI: 0.004, 0.133, P = 0.038), and borderline significantly in episodic memory (0.155 point/year; 95% CI: −0.004, 0.315, P = 0.057). Similarly, significantly slower decline rates were observed in those with LDL-C levels 55–69.9 mg/dL. The present study demonstrated that compared with LDL-C levels 70–99.9 mg/dL, low LDL-C levels (< 70 mg/dL, especially < 55 mg/dL) were associated with significantly slower cognitive decline in population-based setting. Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.