H2 Blockers May Pose Cognitive Function Risk

INDIANAPOLIS, Aug. 6 -- Regular use of histamine-2 receptor antagonists may pose a risk to cognitive function in older African Americans, results of an observational cohort study suggest.Those who used H2RAs to control gastroesophageal reflux were twice as likely as nonusers to develop some degree of, investigators reported in the August issue of the Journal of the American Geriatrics Society.
These findings add to a body of inconsistent research, and warrants further investigation, concluded Malaz Boustani, M.D., of Indiana University, and colleagues.
The proposed study "would need to measure incident cognitive impairment annually or biannually . . . and at the same time collect drug dispensing data to capture continuous exposure to certain medications instead of self-reporting at various time points," the authors stated.
Their findings came from prospective five-year follow-up in the Indianapolis-Ibadan Dementia Project, a study of cognitive function in community-dwelling African-Americans ages 65 and older. The current study included 1,558 participants who were free of cognitive impairment at baseline.
Trained interviewers assessed the use of prescription and nonprescription H2RAs (cimetidine, famotidine, nizatidine, and ranitidine) by means of in-home inspection of medications and reports from participants or family or other close observers. Cognitive function was assessed several times during the follow-up period.
On the basis of the cognitive assessments, participants were separated into good-, intermediate-, and poor-performance groups.
Of the 1,558 participants, 203 were using at least one H2RA during one of the data collection period, including 38 who were classified as continuous users (self-reported use at all data collection periods). The remaining 165 participants were intermittent users.
Analysis of findings from neuropsychological assessments showed that 34.2% of continuous users of H2RAs developed incident cognitive impairment during follow-up, compared with 19.4% of intermittent users and 17% of nonusers (P=0.03).
After adjustment for potential confounding factors, continuous use of H2RAs remained a significant predictor of cognitive impairment compared with nonusers (odds ratio 2.42, P=0.03).
Intermittent use of H2RAs did not increase the risk of cognitive impairment. A separate analysis of the use of proton pump inhibitors also showed no association with cognitive impairment.
Potential mechanisms responsible for an adverse effect of H2RAs on cognitive function are unclear, the authors noted. Explanations that have been offered include H2RA-induced vitamin B12 deficiency and possible central anticholinergic effects of certain H2RAs.
The authors noted several limitations of the study:
Medication use determined by three interviews over five years
Few patients (203 of 1,558, 13%) with H2RA exposure
Generalizability to non-African American populations
Insufficient data to analyze dosage
Nonetheless, the prospective, longitudinal design of the study and the ability to adjust for confounders, strengthen the evidence, they added.
Noting that an estimated 16 million prescriptions for H2RAs are written each year, the magnitude of the potential implications provides a rationale for further studies, they said.
The authors disclosed no conflicts. The study was supported by the National Institute on Aging.Primary source: Journal of the American Geriatrics SocietySource reference: Boustani M et al. "The association between cognition and histamine-2 receptor antagonists in African Americans." J Am Geriatr Soc 2007;55:1248-1253.