Lipid levels and the risk of dementia: A dose–response meta‐analysis of prospective cohort studies

OBJECTIVES: We performed a dose–response meta‐analysis to estimate the association between lipid profiles with the risk of dementia and the potential differences according to the subtype of dementia based on prospective studies. METHODS: We searched PubMed, Embase and Web of Science for relevant articles and performed a meta‐analysis. We applied fixed or random‐effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). The dose–response relationship was assessed by restricted cubic spline. RESULTS: Twenty‐five prospective studies comprising 362,443 participants and 20,121 cases were included in the final analysis. We found that increased risk of all‐cause dementia could be predicted by elevated total cholesterol (TC) (RR = 1.13, 95% CI 1.04–1.22). When looking at dementia subtypes, we also observed high TC and triglycerides (TG) may increase the future risk of Alzheimer's disease (AD), with a pooled RR of 1.13 (95% CI: 1.06–1.21) and 1.10 (95% CI: 1.04–1.15) respectively. Moreover, a dose–response analysis revealed a linear association between TC or TG and the risk of AD, with a pooled RR of 1.09 (95% CI: 1.02–1.16) and 1.12 (95% CI: 1.05–1.21) for per 3‐mmol/L increment in TC and TG, respectively. CONCLUSIONS: Current evidence suggest that every 3‐mmol/L increase in blood TC or TG is linearly associated with a 9% or 12% increase in RR of AD, supporting the notion that high TC and TG levels appear to play a causal role in the development of AD.