Histamine H2 blocking drugs and the risk for Alzheimer's disease: the Rotterdam Study

We investigated the cross-sectional relation of the use of histamine H2 blocking drugs and the risk for AD in the population based Rotterdam Study. AD was clinically diagnosed according to DSM-IIIR and NINCDS-ADRDA criteria. Data on medication used in the past week were obtained by having subjects show vials of medications and were classified according to the Anatomical Therapeutic Chemical (ATC) index. There were 7276 subjects with complete data, including 208 with AD and 378 H2 users (ATC code A0BA). Compared to the total cohort of non-H2 users, the relative risk (estimated as the odds ratio) for AD among those taking H2 blockers was 0.95 (95% confidence interval (CI) 0.52-1.75), after controlling for age, education, sex, history of stroke, and use of benzodiazepines and nonsteroidal antiinflammatory drugs. To address unmeasured confounding (by (contra) indication), we compared the risk of AD in H2 users with a subset of subjects using topical medications (ATC code D and S; n = 436). The adjusted OR in this comparison was 1.24 (95% CI 0.52-2.98). These results do not support the hypothesis that use of histamine H2 blocking drugs protect against AD.