Do PPIs Increase the Risk of Dementia?

Researchers conducted the longitudinal study using data from the National Alzheimer's Coordinating Center
Researchers conducted the longitudinal study using data from the National Alzheimer's Coordinating Center

The use of proton pump inhibitors (PPIs) did not increase the risk of dementia or Alzheimer's disease, according to a study published in the Journal of the American Geriatrics Society

A team of researchers conducted an observational, longitudinal study to evaluate the risk of mild cognitive impairment, dementia, and Alzheimer's disease associated with PPIs. They analyzed data from the National Alzheimer's Coordinating Center (NACC) database from 2005–2015 for patients aged ≥50 with 2–6 annual visits with baseline normal cognition or mild cognitive impairment. Researchers controlled for various demographic factors, vascular comorbidities, mood, and use of anticholinergics, and histamine-2 receptor antagonists.

Of the total patients (n=10,486), 884 were reportedly taking PPIs at every visit, 1,925 reportedly took PPIs intermittently, and 7,677 reported never taking PPIs. The data indicated continuous PPI use was tied to a reduced risk of cognitive function decline vs. never use (hazard ratio [HR] 0.78, 95% CI: 0.66–0.93; P=0.005). Continuous PPI use was also linked to a reduced risk of progressing to mild cognitive impairment or Alzheimer's disease (HR 0.82, 95% CI: 0.69–0.98; P=0.03).  

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Intermittent PPI use was associated with a reduced risk of cognitive function decline (HR 0.84, 95% CI: 0.76–0.93; P=0.001) and risk of progressing to mild cognitive impairment or Alzheimer's disease (HR 0.82, 95% CI: 0.74–0.91; P=0.001). "This lower risk was found for persons with normal cognition or MCI," added lead author Felicia C. Goldstein, PhD. 

Moreover, a significantly higher proportion of PPI users regularly or occasionally had heart disease, diabetes, hypertension, stroke or transient ischemic attack (TIA), and depression, compared to non-users. More PPI users also regularly or occasionally took more anticholinergic drugs, which have also been associated with cognitive impairment. 

The study found contrasting data compared to recent reports of higher risk of dementia or Alzheimer's disease with PPI. More studies are needed to validate these findings "to guide empirically based clinical treatment recommendations," noted Dr. Goldstein.

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