What question did this study set out to answer?

To estimate necessary trial sample sizes and durations for detecting blood pressure-lowering effects on cognitive impairment and dementia.

April 1, 2026

Alternative clinical trial designs to find a clinically important effect size of blood pressure-lowering on cognitive impairment and dementia

Key Result

SPRINT-based blood pressure lowering yielded a 2% relative risk reduction in cognitive impairment, requiring 10-year trials with over 50,000 participants to detect with >80% power.

Key Points

To estimate necessary trial sample sizes and durations for detecting blood pressure-lowering effects on cognitive impairment and dementia.
Used the Michigan Chronic Disease Simulation Model (MICROSIM) for projections.
Simulated outcomes based on demographics and vascular risk factors of the US population.
Evaluated SPRINT-based BP-lowering strategy against usual care for effects on cognition.
Found a 2% relative risk reduction in cognitive impairment from BP-lowering, much lower than the 15% found in related studies.
Ten-year trials with over 50,000 participants are needed to detect a 2% relative risk reduction with >80% power.
Shorter, 5-year trials with 10,000 participants could yield adequate power assuming a 15% relative risk reduction as evidenced in another study.

Structured PICO

Does a SPRINT-based BP-lowering strategy reduce cognitive impairment and dementia in adults with US demographics and vascular risk factors?

Population

Simulated adults with the US population's demographics and vascular risk factors

Intervention

SPRINT-based BP-lowering strategy

Comparator

Usual care

Outcome

Cognitive impairment and dementia (CID) and global cognition

Trials assessing the causal effects of BP-lowering on cognitive impairment and dementia require large sample sizes and long follow-ups unless a large effect size is assumed.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

BackgroundBlood pressure (BP) lowering might reduce the risk of cognitive impairment and dementia (CID), but more information is needed to design trials optimally.ObjectiveTo estimate trial sample sizes and durations for detecting BP-lowering effects on CID.MethodsWe estimated trial sample sizes and durations for finding an effect of a Systolic Blood PRessure INtervention Trial (SPRINT)-based BP-lowering strategy versus usual care on CID and global cognition using our MIchigan ChROnic Disease SIMulation Model (MICROSIM), which simulated adults with the US population's demographics and vascular risk factors and assumed BP-lowering's effect on CID and global cognition from our pooled cardiovascular cohort study.ResultsOver >139 million simulated trials across 78,000 parameters, the SPRINT-based BP-lowering strategy (versus usual care) resulted in a 2% CID relative risk reduction (RRR), much smaller than the CID RRR (15%) found in SPRINT Memory and Cognition IN Decreased Hypertension (MIND). Detecting a 2% CID RRR with >80% power would require 10-year trials with samples >50,000. Identifying the BP-lowering strategy's effect on mean global cognition would require trials of ≥10 years with >30,000 participants. However, trials of 5 years with 10,000 participants would have the power to detect the strategy's effect assuming a 15% CID RRR in SPRINT MIND.ConclusionsIn this microsimulation study, we found that trials would need to be large with long follow-ups to identify the causal effects of BP-lowering on CID and cognition. However, assuming the 15% CID RRR in SPRINT MIND, trials with more feasible sizes and durations could detect those effects.

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