Objectives To investigate whether angiotensin II receptor blockers (ARBs) and ACE inhibitors (ACE-Is) are more strongly associated with Alzheimer's disease (AD) than other anti-hypertensive drugs.

Methods Nested case-control analysis within the UK general practice research database (n≈10 million), with prospectively recorded anti-hypertensive prescribing data. Cases aged ≥60 years and diagnosed between 1997 and 2008 (5797 with AD, 2186 with vascular dementia, 1214 with unspecified / other dementia) were matched to up to four controls by age, general practice and gender. We computed ORs and dose response effects for AD, vascular and unspecified / other dementia, comparing those prescribed ARBs or ACE-Is for at least 6 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 8 years prior to diagnosis / index date.

Results 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 (OR 0.47, 95% CI 0.37 to 0.58) compared with ACE-Is (OR 0.76, 95% CI 0.69 to 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.

Conclusions Patients with AD were around half as likely to be prescribed ARBs. Further randomised controlled trial evidence is required to rigorously test these findings.