PPIs use linked to Incident dementia in regular users

According to a population-based cohort study, regular use of proton pump inhibitors is associated with an increased risk of incident dementia; the relationship is more significant in the APOE ε4 genotype.

The study was published in BMC Medicine by the lead author Peidong Zhang from the Department of Epidemiology, School of Public Health, China.

Proton pump inhibitors (PPI) are easily accessible to the public for over-the-counter purchases. They treat peptic ulcers, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication, and NSAID-associated ulcers. PPIs are commonly prescribed for incorrect indications, both in and out of the hospital, for long-term use that does not meet the criteria.

There is increasing attention given to research on the side effect of PPI with its increasing use. Several cohort studies have reported the association of PPI with all-cause dementia. The hazard ratio of PPI users has been calculated as 1.38 to 1.44. Studies are mentioning conflicting conclusions also. There is still uncertainty in the association of PPI with dementia.

Dementia is a progressive impairment in cognitive and independent living functions. The cases are expected to rise to 65.7 million by 2030. Reducing exposure to risk factors is vital in the ray of limited treatment.

The study enrolled 501,002 participants in the age group 40-70 years, including 54.4 % of females from the UK Biobank between 2006 and 2010. Of this, 53,735 constituting 10 %, were regular users of PPIs. The follow-up was done up to 2018 with nine years of median length. The incidence rates were compared for both users and non-users by the Cox proportional hazard model. The participants had no baseline dementia.

The findings from the study include:

• There were a total of 2505 incident cases of all-cause dementia.
• Nine hundred thirty-two cases of Alzheimer's disease (AD) and 524 (VaD) cases of vascular dementia were reported in the total cases.
• Among PPI users, the incident rate of all-cause dementia was 1.06 events per 1000 person-years.
• Among non-users, the rate was 0.51 events per 1000 person-years.
• The Hazard's ratio for PPI users was 1.20 for incident all-cause dementia, 1.23 for incident AD, and 1.32 for VaD, with P values of 0.001, 0.031, and 0.017, respectively.
• A statistically significant interaction was observed in subgroup analysis to verify the association between PPI use and incident all-cause dementia among the APOE ε4 heterozygotes, with HR of 1.46 and P value of 0.048.
• This association was stronger in females for AD, non-smokers, and participants without stroke for VaD with a P value < 0.05

The study concluded that PPI use increases the risk for all-cause dementia, AD, and VaD. The association is more prominent in AOPE ε4 heterozygotes.

The study has extensive results providing valid observations consistent with the previous studies. The high-quality evidence of the study is beneficial in future controlled trials to verify this causal relationship.

Reference:

Zhang, P., Li, Z., Chen, P. et al. Regular proton pump inhibitor use and incident dementia: population-based cohort study. BMC Med 20, 271 (2022)