Antihypertensive Medication Adherence, APOE Genotype, and Subsequent Dementia in Community-Dwelling Adults ≥50 Years

BACKGROUND: We aim to examine prospective associations of longitudinal adherence to antihypertensive medication, APOE ε4 carrier, and subsequent dementia risk in community-dwelling middle-aged and older adults. METHODS: A longitudinal cohort using 12-year survey data from wave 8 (2006) to wave 14 (2018) in the Health and Retirement Study, an ongoing national survey recruiting community-dwelling adults aged ≥50 years in the United States. Longitudinal adherence to antihypertensive medication was evaluated during wave 8 (2006) to wave 10 (2010), based on self-reported antihypertensive medication use at each wave. Incident dementia cases were ascertained during wave 10 (2010) to wave 14 (2018) by combining self-reported diagnosis and standardized cognitive batteries, excluding prevalent cases during the medication adherence evaluation period. Cox proportional hazard regression was utilized to assess dementia risk, with adjusted hazard ratios (HR) and 95% CIs calculated, controlling for sociodemographic characteristics, socioeconomic status indicators, lifestyle factors, and clinical conditions, as well as blood pressure measurements. RESULTS: A total of 18 469 participants were screened, after which 11 835 participants (mean [SD] age: 66.2 [10.1] years; men: 40.6%) were included, with 1136 incident dementia cases. After controlling blood pressure and other known risk factors, hypertension participants who persistently adhered to antihypertensive medication during follow-up had a 27% lower dementia risk (HR, 0.73 [95% CI, 0.61–0.87]) than the low adherence group, which was more evident than the associations between baseline antihypertensive medication use and dementia. The difference in dementia risk was insignificant when comparing the high adherence group with the normotension group (HR, 1.03 [95% CI, 0.88–1.21]). The results were consistent in non- APOE ε4 carriers (HR, 0.73 [95% CI, 0.59–0.89]) versus APOE ε4 carriers (HR, 0.75 [95% CI, 0.55–1.02]; P for interaction: 0.939). CONCLUSIONS: Persistently adhering to antihypertensive medication was consistently associated with a lower subsequent dementia risk in community-dwelling middle-aged and older adults.