Blood Cholesterol and Risk of Dementia in a Retrospective Cohort of Over 1.8 Million People Over Two Decades

Background: Uncertainty remains around the association of blood cholesterol with risk of subsequent dementia.  Methods: We studied a cohort from the United Kingdom Clinical Practice Research Datalink of people aged 40 years or older with a first total cholesterol (TC) recording between 1992 and 2009. Follow-up was until the first record of dementia, the last data collection date, the patient’s death/transfer out of the practice, or January 2015. We excluded people with a record of dementia before the TC measurement. We used Poisson regression to examine the association of baseline TC, low and high-density lipoprotein cholesterol (LDL-C and HDL-C), and triglycerides with incident dementia diagnosis. Analyses were stratified by age at measurement (<65 or ≥65 years) and duration of follow-up (<10 or ≥10 years). Findings: There were 1,853,954 people with a first TC recording (dementia occurring in 49,416), including 953,635 people with LDL-C values for analysis (dementia occurring in 21,602). Overall, there was a modest positive association between LDL-C with dementia, with an adjusted rate ratio of 1·05 (95% confidence interval, 1·03–1·06) per standard deviation (SD) increase (1·01 mmol/l). Adjusted risk ratios per 1-SD increase in LDL-C in people aged <65 years at baseline (n=636,262), were 1·10 (1·04–1·15) for dementia diagnosed in the first 10 years after measurement and 1·17 (1·08–1·27) more than 10 years after measurement. Associations for LDL-C in people age ≥65 years at baseline (n=317,373) were weaker: 1·03 (1·01–1·05) for dementia diagnosed during the first 10 years of follow-up and 1·07 (1·03–1·13) thereafter. There was a weaker association with TC and no consistent associations for HDL-C and triglycerides.  Interpretation: LDL-C measured in midlife is modestly associated with dementia risk more than 10 years later. HDL-C and triglycerides are not associated with dementia risk. Funding: The Alzheimer’s Society, UK (grant 280). Declaration of Interest: We declare no competing interests. Ethical Approval: This study was approved by the Medicines and Healthcare products Regulatory Agency’s Independent Scientific Advisory Committee (protocol number 15_148R).