Abstract
Background: Prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRDs) are urgently needed for reducing incidence. Intra-patient variability in lipid levels is a potentially modifiable risk factor for incident AD/ADRD. Although regular lipid measurements are a part of common clinical practice and longitudinal data routinely available in electronic health records (EHR), research examining this association between AD/ADRD and lipid variability across multiple lipid types remains scarce. Methods: All residents living in Olmsted County, MN on 1/1/2006 age ≥60 years without an AD/ADRD diagnosis were identified using Centers for Medicare & Medicaid Services diagnostic codes. Persons with ≥3 lipid measurements (total cholesterol or triglycerides) in the 5 years prior to index date were retained. Lipid variability was quantified using variability independent of the mean (VIM). Models were adjusted for traditional risk factors. Associations between lipid variability quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Multiple imputation was used for missing covariates. Participants were followed through 2018 for incident AD/ADRD. Results: The final analysis included data on 11,551 participants with total cholesterol and 11,502 participants with triglycerides. Participants had a mean age of 71 (range 60-99) years, and were primarily white (96%). Females (54%) were also slightly more frequent than males. Median follow up was 12.9 years (range: 0-13). Participants in the highest quintile of variability for total cholesterol and triglycerides had a 20% increased risk of incident AD/ADRD. Similar results were found in the subset with complete covariate data. Conclusion: In a large EHR derived cohort, persons in the highest quintile of lipid variation had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this risk factor and replication of these results across a more diverse population are needed.
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