Associations of Anti-Hypertensive Treatments with Alzheimer's Disease, Vascular Dementia, and Other Dementias

Article type: Research Article

Authors: Davies, Neil M.^{a; b} | Kehoe, Patrick G^{c; *} | Ben-Shlomo, Yoav^a | Martin, Richard M.^{a; b}

Affiliations: [a] School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Canynge Hall, Bristol, UK | [b] MRC Centre for Causal Analysis in Translational Epidemiology (CAiTE), University of Bristol, Oakfield House, Bristol, UK | [c] Dementia Research Group, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, John James Laboratories, Frenchay Hospital, Bristol, UK

Correspondence: [*] Correspondence to: Dr. Patrick G Kehoe, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, John James Laboratories, Frenchay, Hospital, Bristol BS16 1LE. Tel.: +44 (0) 117 340 6607; Fax: +44 (0) 117 340 6665; E-mail: Patrick.Kehoe@bristol.ac.uk.

Abstract: We investigated whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACE-Is) are more strongly associated with Alzheimer's disease (AD), vascular dementia (VaD), and other dementias, than other anti-hypertensive drugs. We conducted a nested case-control analysis within the UK general practice research database, with prospectively recorded anti-hypertensive prescribing data. We sampled cases aged ≥60 years and diagnosed between 1997–2008 (5,797 with AD, 2,186 with VaD, 1,214 with unspecified/other dementia) which were matched to up to four controls by age, general practice and gender. We computed odds-ratios and dose response effects for AD, vascular and unspecified/other dementia, comparing those prescribed ARBs or ACE-Is for at least six months with patients prescribed other anti-hypertensives. We controlled for matching factors, co-morbidities, smoking status, an area measure of socioeconomic status, consultation rate and blood pressure and accounted for reverse causality by introducing time-lags of up to eight years prior to diagnosis/index date. Patients diagnosed with AD, vascular and unspecified/other dementia had fewer prescriptions for ARBs and ACE-Is. Inverse associations with AD were strongest for ARBs (odds-ratio; 0.47, 95%CI, 0.37–0.58) compared with ACE-Is (odds-ratio; 0.76, 95%CI, 0.69–0.84) (pdifference < 0.001). Associations of ARBs with AD were stronger than for vascular dementia (pdifference = 0.01) and unspecified/other dementia (pdifference = 0.23). There were inverse dose-response relationships between ARBs and ACE-Is with AD (both ptrend < 0.01). The inverse association of ACE-Is with AD diminished when using longer time lags but the ARB-AD association persisted. Patients with AD were around half as likely to be prescribed ARBs. Further randomized controlled trial evidence is required to rigorously test these findings.

Keywords: All cognitive disorders/dementia, Alzheimer's disease, case control studies, risk factors in epidemiology, vascular dementia

DOI: 10.3233/JAD-2011-110347

Journal: Journal of Alzheimer's Disease, vol. 26, no. 4, pp. 699-708, 2011