Alternative clinical trial designs to find a clinically important effect size of blood pressure-lowering on cognitive impairment and dementia
Year: 2026
Type: article
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.
Source: Journal of Alzheimer s Disease
Institutions: University of Michigan, VA Center for Clinical Management Research, Johns Hopkins University, Michigan Medicine, Columbia University, National Institute of Neurological Disorders and Stroke, Kaiser Permanente, Kaiser Permanente Northern California, University of California, San Francisco, The Ohio State University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG), CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, CHS research resources for the cardiovascular health of older adults, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG), ARIC Neurocognitive Study (ARIC-NCS) Renewal UNC 4 of 5, ARIC Neurocognitive Study (ARIC-NCS) Renewal 4 of 5, The Effect of Vascular Risk Factors on Risk of Alzheimer's Disease and Related Dementias after Stroke (STROKE COG), Risk Factors for Stroke and Cognitive Decline in a Tri-Ethnic Region, CHS Events Follow-up Study, Intersection of Physiologic Frailty and Cognitive Performance in Older Adults: An Integrative Data Analysis, CHS-Transition Phase, ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5, ARIC Neurocognitive Study (ARIC-NCS), Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), Michigan Diabetes Research Center (MDRC), Michigan Alzheimer's Disease Research Center, ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028, Claude D. Pepper Older Americans Independence Center at the University of Michigan (UM Pepper Center), Johns Hopkins Alzheimer's Disease Research Center, Infrastructure for mentored access to CHS data and specimens, Measurement of cognition and functional decline in Latinx older adults for detection of Alzheimer’s Disease and Related Dementias: A mixed-methods approach
OpenAlex ID: W7143437773