title: Associations of anti-hypertensive treatments with Alzheimer's disease, vascular dementia, and other dementias.
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) (p(difference) < 0.001). Associations of ARBs with AD were stronger than for vascular dementia (p(difference) = 0.01) and unspecified/other dementia (p(difference) = 0.23). There were inverse dose-response relationships between ARBs and ACE-Is with AD (both p(trend) < 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.
authors.affiliation: School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Canynge Hall, Bristol, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Davies
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D003704:Dementia / Q000453:epidemiology*; D015140:Dementia, Vascular / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012959:Socioeconomic Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents