In the Journals

PPIs may increase risk for dementia

Regular use of proton pump inhibitors was found to be associated with an increased risk for incident dementia in older patients, according to results from a prospective cohort study.

Previously, Britta Haenisch, PhD, of the German Center for Neurodegenerative Diseases in Bonn, Germany, and colleagues analyzed data from a prospective, longitudinal, multicenter cohort study of 3,327 older primary care patients and found a significant association between PPI use and incident dementia (HR = 1.38; 95% CI, 1.04-1.83). To confirm these findings, the research team evaluated 2004 to 2011 observational data from Allgemeine Ortskrankenkassen, the largest German statutory health insurer, on 73,679 patients aged at least 75 years.

Only patients without dementia at baseline, and with no use or regular use of PPIs, were included in the analysis, with regular use defined as at least one prescription to omeprazole, pantoprazole, lansoprazole, esomeprazole or rabeprazole in each quarter of a data interval (1-year baseline followed by 18-month intervals and a final 12-month interval).

Diagnosis of incident dementia served as the primary outcome, and the research team used time-dependent Cox regression analysis to determine the association between PPI use and dementia, adjusting for potential confounders including age, sex, comorbidities and polypharmacy.

Patients who regularly received PPIs (n = 2,950; mean age, 83.8 ± 5.4 years; 77.9% women) had a significantly increased risk for dementia compared with patients who did not receive PPIs (n = 70,729; mean age, 83 ± 5.6 years; 73.6% women; HR = 1.44; 95% CI, 1.36-1.52).

Risk for incident dementia with PPI use was slightly higher in men vs. women. A subgroup analysis of the three most commonly prescribed PPIs showed comparable elevated risks for dementia associated with omeprazole and pantoprazole, but a slightly higher risk associated with esomeprazole.

“The avoidance of PPI medication may contribute to the prevention of dementia,” the researchers concluded. “The present study can only provide a statistical association between PPI use and risk of dementia. The possible underlying causal biological mechanism has to be explored in future studies.”

This study has “provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia,” Lewis H. Kuller, MD, DrPH, of the University of Pittsburgh, wrote in a related editorial. “This is a very important issue given the very high prevalence of pharmacological drugs’ long-term use in elderly populations that have a very high risk of dementia. An important issue raised by this study and similar studies of drugs that may increase risk of dementia is whether a careful evaluation of cognitive changes and/or neuropathology should be a component of the evaluation of drugs that are widely used among the elderly.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.

Regular use of proton pump inhibitors was found to be associated with an increased risk for incident dementia in older patients, according to results from a prospective cohort study.

Previously, Britta Haenisch, PhD, of the German Center for Neurodegenerative Diseases in Bonn, Germany, and colleagues analyzed data from a prospective, longitudinal, multicenter cohort study of 3,327 older primary care patients and found a significant association between PPI use and incident dementia (HR = 1.38; 95% CI, 1.04-1.83). To confirm these findings, the research team evaluated 2004 to 2011 observational data from Allgemeine Ortskrankenkassen, the largest German statutory health insurer, on 73,679 patients aged at least 75 years.

Only patients without dementia at baseline, and with no use or regular use of PPIs, were included in the analysis, with regular use defined as at least one prescription to omeprazole, pantoprazole, lansoprazole, esomeprazole or rabeprazole in each quarter of a data interval (1-year baseline followed by 18-month intervals and a final 12-month interval).

Diagnosis of incident dementia served as the primary outcome, and the research team used time-dependent Cox regression analysis to determine the association between PPI use and dementia, adjusting for potential confounders including age, sex, comorbidities and polypharmacy.

Patients who regularly received PPIs (n = 2,950; mean age, 83.8 ± 5.4 years; 77.9% women) had a significantly increased risk for dementia compared with patients who did not receive PPIs (n = 70,729; mean age, 83 ± 5.6 years; 73.6% women; HR = 1.44; 95% CI, 1.36-1.52).

Risk for incident dementia with PPI use was slightly higher in men vs. women. A subgroup analysis of the three most commonly prescribed PPIs showed comparable elevated risks for dementia associated with omeprazole and pantoprazole, but a slightly higher risk associated with esomeprazole.

“The avoidance of PPI medication may contribute to the prevention of dementia,” the researchers concluded. “The present study can only provide a statistical association between PPI use and risk of dementia. The possible underlying causal biological mechanism has to be explored in future studies.”

This study has “provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia,” Lewis H. Kuller, MD, DrPH, of the University of Pittsburgh, wrote in a related editorial. “This is a very important issue given the very high prevalence of pharmacological drugs’ long-term use in elderly populations that have a very high risk of dementia. An important issue raised by this study and similar studies of drugs that may increase risk of dementia is whether a careful evaluation of cognitive changes and/or neuropathology should be a component of the evaluation of drugs that are widely used among the elderly.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.