Abstract Background The relationship between frailty and dementia risk in hypertensive patients remains unclear, as does the impact of frailty on the effectiveness of antihypertensive treatment in preventing dementia. Methods Using data from the Systolic Hypertension in the Elderly Program trial, a baseline frailty index (FI) including 55 health deficits was constructed. Multinomial regression models were used to examine the association between frailty and dementia, as well as to examine whether the impact of antihypertensive treatment on the risk of dementia was modified by baseline FI. Results A total of 4692 participants (mean age: 72.1 years, 56.8% female) were included with a median (inter-quartile interval) FI of 0.127 (0.091–0.173). During a median follow-up of 4.4 years, 81 dementia cases occurred. Each SD (0.061) increase in FI was associated with a 33% higher risk of dementia odds ratio (OR): 1.33, 95% confidence interval (CI): 1.08–1.64, after adjusting for age, sex, race, education and treatment group. This association differed between the active treatment group (OR: 1.57; 95% CI: 1.16–2.11) and the placebo group (OR: 1.17; 95% CI: 0.87–1.56), with a P for interaction = .049. Correspondingly, in the lowest FI quarter, antihypertensive treatment reduced dementia risk (OR: 0.19, 95% CI: 0.04–0.94), an effect not observed in higher FI quarters (interaction P = .058). Conclusion In patients with isolated systolic hypertension, frailty may serve as a risk factor for dementia, and elevated levels of frailty may attenuate the effectiveness of antihypertensive treatment in reducing dementia risk.
Chen et al. (2026) studied this question.