This nationwide target trial emulation compared new initiation of angiotensin receptor blockers (ARBs) vs. calcium channel blockers (CCBs) on incident dementia risk in dementia-free Japanese adults aged ≥65 years, using the LIFE database (April 2014–September 2024), with median follow-up of 3.6 years (n=52,019).
ARB initiation was associated with lower all-cause dementia risk vs. CCB (ITT HR 0.916, 95% CI 0.852–0.985; 5-year risk 8.0% vs. 8.8%, absolute risk difference −0.8 pp). The effect was strongest for vascular dementia (HR 0.617, 95% CI 0.409–0.930) but not statistically significant for Alzheimer's disease (HR 0.930, 95% CI 0.849–1.018). Achieved blood pressure was nearly identical between groups (<1 mmHg difference at each follow-up year).
- Residual confounding from unmeasured factors (education, socioeconomic status, baseline cognition, BP variability) cannot be excluded. - Dementia diagnosis and subtype classification relied on ICD-10 administrative codes, risking nondifferential misclassification that could attenuate associations. - Findings are from a Japanese cohort; generalizability to other healthcare systems with different prescribing patterns is uncertain.
When selecting a first-line antihypertensive in older adults where ARBs and CCBs are otherwise equivalent, ARB-based therapy may offer a modest cognitive benefit—particularly for vascular dementia—beyond blood pressure control alone. The absolute risk difference is small (~0.8 pp over 5 years), so individual comorbidities, tolerability, and patient preference should still guide choice.
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