Association of Antihypertensives and Cognitive Impairment in Long-Term Care Residents

Article type: Research Article

Authors: Marcum, Zachary A.^a | Li, Yongmei^b | Lee, Sei J.^{c; d} | Steinman, Michael A.^{c; d} | Graham, Laura^{e; f} | Jing, Bocheng^g | Fung, Kathy^{c; d} | Peralta, Carmen A.^h | Odden, Michelle C.^{b; i}

Affiliations: [a] Department of Pharmacy, University of Washington, Seattle, WA, USA | [b] Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA | [c] San Francisco VA Medical Center, San Francisco, CA, USA | [d] Department of Medicine, University of California San Francisco, San Francisco, CA, USA | [e] Department of Surgery, Stanford University, Stanford, CA, USA | [f] Health Economics Research Center, VA Palo Alto Health Care System, Palo Alto, CA, USA | [g] NCIRE – The Veterans Health Research Institute, San Francisco, CA, USA | [h] Cricket Health, Inc and the Kidney Health Research Collaborative, University of California San Francisco and San Francisco VA Medical Center, San Francisco, CA, USA | [i] Geriatric Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USA

Correspondence: [*] Correspondence to: Zachary A. Marcum, PharmD, PhD, Department of Pharmacy, School of Pharmacy, University of Washington, 1959 NE Pacific St, Box 357630, Seattle, WA 98102, USA. Tel.: 206 685 2559; Fax: 206 543 3835; E-mail: [email protected]; @zacharyamarcum.

Abstract: 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 + years 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-‘stimulating’ (N = 589), ‘inhibiting’ (N = 3,219), or ‘mixed’ (N = 1,715) 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 ‘stimulating’ antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively ‘inhibiting’ antihypertensives (HR 0.83, 95% CI 0.74–0.93). Results for the comparison between ‘mixed’ versus ‘inhibiting’ regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88–1.06). 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.

Keywords: Aged, antihypertensive drugs, antihypertensives, cognitive dysfunction

DOI: 10.3233/JAD-215393

Journal: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 1149-1158, 2022