Initiation of Antihypertensive Medication from Midlife on Incident Dementia: The Health and Retirement Study

Article type: Research Article

Authors: Wei, Jingkai^{a; *} | Xu, Hanzhang^{b; c} | Zhang, Donglan^{d; e} | Tang, Huilin^f | Wang, Tiansheng^g | Steck, Susan E.^a | Divers, Jasmin^{d; e} | Zhang, Jiajia^a | Merchant, Anwar T.^a

Affiliations: [a] Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA | [b] Department of Family Medicine and Community Health, School of Medicine, Duke University, Durham, NC, USA | [c] School of Nursing, Duke University, Durham, NC, USA | [d] New York University Langone Health, New York, NY, USA | [e] Long Island School of Medicine, New York University, New York, NY, USA | [f] Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA | [g] Department of Epidemiology, Gilllings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Correspondence: [*] Correspondence to: Jingkai Wei, PhD, MSPH, 915 Greene St, Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA. E-mail: [email protected].

Abstract: Background:Hypertension has been identified as a risk factor of dementia, but most randomized trials did not show efficacy in reducing the risk of dementia. Midlife hypertension may be a target for intervention, but it is infeasible to conduct a trial initiating antihypertensive medication from midlife till dementia occurs late life. Objective:We aimed to emulate a target trial to estimate the effectiveness of initiating antihypertensive medication from midlife on reducing incident dementia using observational data. Methods:The Health and Retirement Study from 1996 to 2018 was used to emulate a target trial among non-institutional dementia-free subjects aged 45 to 65 years. Dementia status was determined using algorithm based on cognitive tests. Individuals were assigned to initiating antihypertensive medication or not, based on the self-reported use of antihypertensive medication at baseline in 1996. Observational analog of intention-to-treat and per-protocol effects were conducted. Pooled logistic regression models with inverse-probability of treatment and censoring weighting using logistic regression models were applied, and risk ratios (RRs) were calculated, with 200 bootstrapping conducted for the 95% confidence intervals (CIs). Results:A total of 2,375 subjects were included in the analysis. After 22 years of follow-up, initiating antihypertensive medication reduced incident dementia by 22% (RR = 0.78, 95% CI: 0.63, 0.99). No significant reduction of incident dementia was observed with sustained use of antihypertensive medication. Conclusion:Initiating antihypertensive medication from midlife may be beneficial for reducing incident dementia in late life. Future studies are warranted to estimate the effectiveness using large samples with improved clinical measurements.

Keywords: Aging, Alzheimer’s disease, antihypertensive medication, causal effect, dementia, emulated target trial, hypertension, midlife

DOI: 10.3233/JAD-230398

Journal: Journal of Alzheimer's Disease, vol. 94, no. 4, pp. 1431-1441, 2023