To the Editor I read with interest the article by Gomm et al1 investigating the association of proton pump inhibitors and dementia. The authors are to be commended for their large data set, analysis, and detailed proposed pathophysiologic mechanism by which this association might occur. However, 2 important medical comorbidities seem to be missing from their study: gastroesophageal reflux disease and obstructive sleep apnea. Both of these comorbidities can cause cognitive issues, especially in those with apolipoprotein E genetic variants2 and those who have had a stroke. Gastroesophageal reflux disease would constitute the reason patients took a proton pump inhibitor but could also be a surrogate for obesity, increased body mass index, and comorbid obstructive sleep apnea. Obstructive sleep apnea is a known risk factor for nocturnal hypoxic episodes and could, in theory, be covariate to help explain why this association may be statistically present.
Freeman WD. Proton Pump Inhibitors and Dementia Incidence. JAMA Neurol. 2016;73(8):1026-1027. doi:10.1001/jamaneurol.2016.1503