{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:54:39Z","timestamp":1777395279580,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,4,5]]},"abstract":"<jats:p>Background: Certain classes of antihypertensive medication may have different associations with cognitive impairment. Objective: To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care. Methods: Retrospective cohort study. Long-term care residents aged 65\u200a+\u200ayears admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-\u2018stimulating\u2019 (N\u200a=\u200a589), \u2018inhibiting\u2019 (N\u200a=\u200a3,219), or \u2018mixed\u2019 (N\u200a=\u200a1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale). Results: Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively \u2018stimulating\u2019 antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively \u2018inhibiting\u2019 antihypertensives (HR 0.83, 95% CI 0.74\u20130.93). Results for the comparison between \u2018mixed\u2019 versus \u2018inhibiting\u2019 regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88\u20131.06). Conclusion: For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.<\/jats:p>","DOI":"10.3233\/jad-215393","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T10:39:20Z","timestamp":1644575960000},"page":"1149-1158","source":"Crossref","is-referenced-by-count":8,"title":["Association of Antihypertensives and Cognitive Impairment in Long-Term Care Residents"],"prefix":"10.1177","volume":"86","author":[{"given":"Zachary A.","family":"Marcum","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sei J.","family":"Lee","sequence":"additional","affiliation":[{"name":"San Francisco VA Medical Center, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Steinman","sequence":"additional","affiliation":[{"name":"San Francisco VA Medical Center, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University, Stanford, CA, USA"},{"name":"Health Economics Research Center, VA Palo Alto Health Care System, Palo Alto, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bocheng","family":"Jing","sequence":"additional","affiliation":[{"name":"NCIRE \u2013 The Veterans Health Research Institute, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Fung","sequence":"additional","affiliation":[{"name":"San Francisco VA Medical Center, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen A.","family":"Peralta","sequence":"additional","affiliation":[{"name":"Cricket Health, Inc and the Kidney Health Research Collaborative, University of California San Francisco and San Francisco VA Medical Center, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle C.","family":"Odden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA"},{"name":"Geriatric Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-215393_ref1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet Commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"10.3233\/JAD-215393_ref2","doi-asserted-by":"crossref","unstructured":"National Academies of Sciences, Engineering, and Medicine (2017) Preventing Cognitive Decline and Dementia: A Way Forward. 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Effect of intensive vs standard blood pressure control on probable dementia: A randomized clinical trial","volume":"321","author":"Williamson","year":"2019","journal-title":"JAMA"},{"key":"10.3233\/JAD-215393_ref4","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3233\/JAD-171119","article-title":"The coming of age of the angiotensin hypothesis in Alzheimer\u2019s disease: Progress toward disease prevention and treatment?","volume":"62","author":"Kehoe","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-215393_ref5","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1136\/hrt.2006.107706","volume":"93","author":"Brown","year":"2007","journal-title":"Heart"},{"key":"10.3233\/JAD-215393_ref6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.phrs.2017.07.008","article-title":"AT2 receptors in cardiovascular and renal diseases","volume":"125","author":"Kaschina","year":"2017","journal-title":"Pharmacol 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