Abstract 4147275: A Longitudinal 20-year Analysis Indicates Acceleration of Cardiometabolic Comorbidities on Dementia Risk

Background: Dementia often seen in people aged ≥65y years is a major public health burden in Hong Kong, as its men and women have one of the longest lifespan worldwide. Using territory wide electronic health records (EHRs) spanning >20 years, we investigated the impact of cardiometabolic comorbidities on dementia risk. Methods: EHRs of public hospitals provided by Hong Kong’s Hospital Authority (HADCL) were examined for patient visits from 01/01/2000 to 12/31/2020. Included were individuals born in 1920,1930,1940,1950 with ICD-10 codes for all-cause dementia, or use of dementia and/or psychotropic drugs. Atrial fibrillation, stroke, hypertension, myocardial infarction, diabetes mellitus, chronic kidney disease, and hyperlipidemia identified by ICD codes or dispensed diabetic drug(s) or dihydropyridine calcium channel blocker (for hypertension) were investigated for age-dependent association with dementia using landmark analysis with multivariate Cox models. Results: A total of 222,418 patients (49% female) in four birth cohorts were examined with landmark analysis, which showed similar incidences for dementia. Adjusted for multiple testing, increased risk of all-cause dementia stratified by birth cohorts were significantly associated with hypertension and stroke from age 65, diabetes from age 50, and chronic kidney disease among men from age 58–64 (Figure). Earlier onset of these comorbidities except for hypertension were associated with increased dementia risk. Moreover, while the risk of dementia declined with old age in patients with diabetes, the risk for dementia markedly increased with hypertension after age 80. Surprisingly, the most recent birth cohorts, especially males, showed dementia risk elevation with diabetes, stroke and chronic kidney disease. Conclusion: We showed hypertension is a major risk for dementia in men/women >80 years, indicating hypertension management is critical for dementia risk reduction in the aged. The increase in dementia risk with stroke, diabetes, and chronic renal disease in the recent birth cohorts indicates disease burden acceleration predicting increase in economic burden. Further studies are warranted to investigate possible epigenetic mechanisms modulating dementia risk.