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PPI does not up dementia risk

Pearl Toh
13 Jul 2017

Proton pump inhibitors (PPIs) were not associated with a higher risk of dementia or Alzheimer's disease (AD), in contrast to recent studies.

The observational, longitudinal study included 10,486 participants (aged ≥50 years) with baseline normal cognition or mild cognitive impairment (MCI), of which 884 reported always taking PPIs at every study visit (2–6 visits yearly), 1,925 reported taking PPIs intermittently, and 7,677 never reported using any PPI during any visit. [J Am Geriatr Soc 2017;doi:10.1111/jgs.14956]

Among individuals with normal baseline cognition, those who always took PPIs had a lower risk of cognitive decline than those who never did (hazard ratio [HR], 0.78; p=0.005). Similarly, a reduced risk of cognitive decline was also observed with intermittent use of PPI (HR, 0.84; p=0.001). 

In an already vulnerable group comprising individuals with MCI at baseline, both consistent and intermittent use of PPIs was associated with a lower risk of progression from MCI to AD compared with nonuse (HR, 0.82; p=0.03 for consistent use and HR, 0.82; p=0.001 for intermittent use).

In addition, individuals with baseline MCI who used PPIs intermittently also had a lower risk of cognitive decline with a suspected AD cause (HR, 0.86; p=0.03).

“The current findings do not support that PPIs are associated with greater risk of dementia despite mechanisms proposed as to why they should be,” said the researchers.

Potential mechanisms that were believed to underlie the association between PPIs and cognitive function included high β-amyloid levels or vitamin B12 deficiency, which have been observed with PPI use in previous studies. [PLoS ONE 2013;8:e58837; JAMA 2013;310:2435-2442]

While the current results corroborate a recent study which found no association between PPIs and dementia, [Int Psychogeriatr 2016;28:1059-1065] they are in conflict with another two reports, which implied a detrimental effect of PPIs on cognition of persons aged ≥75 years, raising concerns about widespread use of PPIs in the elderly, noted the researchers. [Eur Arch Psychiatry Clin Neurosci 2015;265:419-428; JAMA Neurol 2016;73:410-416]

However, a subgroup analysis in the current study which was restricted only to individuals aged ≥75 years showed that the risk of cognitive decline was significantly reduced with intermittent (HR, 0.85; p=0.009) and consistent PPI use (HR, 0.81; p=0.049) compared with nonuse among individuals with normal cognition or MCI, but not dementia, at baseline.

“It is possible that the PPI users, because of the greater frequency of cardiovascular risk factors [in this study], received better health care than non-PPI users. This, in turn, could have reduced their risk of dementia,” said the researchers.

“Caution needs to be exercised when speculating about the effect of PPIs on brain functioning until a randomized, prospective clinical trial elucidates the effect of PPIs on cognition,” they advised. 

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