{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:14:20Z","timestamp":1783415660413,"version":"3.54.6"},"reference-count":34,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS102715"],"award-info":[{"award-number":["R01 NS102715"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood pressure (BP) lowering might reduce the risk of cognitive impairment and dementia (CID), but more information is needed to design trials optimally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To estimate trial sample sizes and durations for detecting BP-lowering effects on CID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over &gt;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 &gt;80% power would require 10-year trials with samples &gt;50,000. Identifying the BP-lowering strategy's effect on mean global cognition would require trials of \u226510 years with &gt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261430953","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:57:32Z","timestamp":1774879052000},"page":"211-221","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternative clinical trial designs to find a clinically important effect size of blood pressure-lowering on cognitive impairment and dementia"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-8001","authenticated-orcid":false,"given":"Deborah A.","family":"Levine","sequence":"first","affiliation":[{"name":"University of Michigan (U-M)"},{"name":"Institute for Healthcare Policy and Innovation, U-M, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney A.","family":"Hayward","sequence":"additional","affiliation":[{"name":"Institute for Healthcare Policy and Innovation, U-M, Ann Arbor, MI, USA"},{"name":"Ann Arbor Veteran's Affairs Hospital, Center for Clinical Management and Research, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy B.","family":"Sussman","sequence":"additional","affiliation":[{"name":"Institute for Healthcare Policy and Innovation, U-M, Ann Arbor, MI, USA"},{"name":"Ann Arbor Veteran's Affairs Hospital, Center for Clinical Management and Research, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael T.","family":"Whitney","sequence":"additional","affiliation":[{"name":"University of Michigan (U-M)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej T.","family":"Ga\u0142ecki","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, U-M, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Brice\u00f1o","sequence":"additional","affiliation":[{"name":"University of Michigan (U-M)"},{"name":"Department of Physical Medicine and Rehabilitation, U-M, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alden L.","family":"Gross","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno J.","family":"Giordani","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Michigan Alzheimer's Disease Center, U-M, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-1156","authenticated-orcid":false,"given":"Mitchell S. V.","family":"Elkind","sequence":"additional","affiliation":[{"name":"Columbia University"},{"name":"Columbia University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell J.","family":"Gaskin","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca F.","family":"Gottesman","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Yaffe","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Neurology and Epidemiology, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ohio State College of Medicine, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_3_3_2_2","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019","volume":"7","author":"GBD 2019 Dementia Forecasting Collaborators","year":"2022","unstructured":"GBD 2019 Dementia Forecasting Collaborators. 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