Table 6.

Randomized trials with cognitive endpoints relevant to cardiovascular prevention

Trial (year)	Design	Population	Cognitive endpoint	Result	Implication
SPRINT MIND (2019)	RCT substudy, intensive (< 120) vs. standard (< 140 mmHg)	Hypertensive adults without diabetes or prior stroke	Probable dementia; MCI (secondary)	No significant dementia reduction; significant MCI and combined MCI + dementia reduction; likely underpowered after early termination	BP lowering reduces MCI and slows WMH progression
FINGER (2015)	RCT, multidomain lifestyle vs. health advice	At-risk older adults, Finland	Neuropsychological composite	Improved or maintained cognition vs. control	Multidomain risk reduction benefits cognition
US POINTER (2025)	Phase 3 single-blind RCT, structured vs. self-guided lifestyle, 2 years	2111 adults aged 60–79 at risk	Global cognitive composite	Both arms improved; structured arm greater; consistent across subgroups	Lifestyle intervention protects cognition in diverse population; no usual-care control
BRAIN-AF (2026)	Double-blind RCT, rivaroxaban vs. placebo/aspirin	Adults < 65 with nonvalvular AF at low stroke risk	Composite of stroke, TIA, cognitive decline (MoCA)	Stopped for futility; HR 1.10	Anticoagulating low-risk AF does not prevent cognitive decline
LACI-2 (2023)	Phase 2b RCT, ISMN and/or cilostazol vs. guideline care, 2 × 2 factorial, 12 months	363 adults with lacunar stroke	Cognitive impairment (DSM-5 7-level ordinal), tMoCA	Combination aOR 0.44, improved tMoCA, reduced low mood; cilostazol alone reduced impairment at 6 months	Substrate-directed endothelial therapy feasible and promising; phase 3 warranted
CREST-2 cognitive substudy (2026)	Substudy of RCT, revascularization + intensive medical vs. intensive medical alone	> 2000 adults with asymptomatic carotid stenosis	Longitudinal cognitive trajectory	No divergence; no benefit even with worse baseline cognition	Revascularization does not protect cognition; decline is multifactorial