Proton pump inhibitors (PPIs) are effective and suppressing acid, and therefore have effi cacy against gastric acid-related disorders. The long-term safety of PPIs is less clear and there have been a number of studies raising concerns regarding risk of pneumonia, fracture, Clostridium diffi cile , chronic renal failure, and dementia. This latter concern is addressed by a study in this issue of AJG using health care registry data and found there was no association between PPI use and Alzheimer's dementia. Furthermore, there was no increased risk of dementia with long-term use of PPIs or higher doses of PPIs. Discrepancies between studies probably relate to multiple testing and residual confounding and currently there is insuffi cient evidence to suggest that the association between PPIs and dementia is causal. Am J Gastroenterol 2017; 112:1809-1811 doi: 10.1038/ajg.2017 Proton pump inhibitors (PPIs) have been one of the major innovations in gastroenterology over the last 30 years. Th ey are extremely eff ective in treating gastro-esophageal refl ux disease ( 1 ) and indications have expanded to include diverse conditions such as prevention of peptic ulcer bleeding and functional dyspepsia ( 2 ). PPIs have also been extremely lucrative for the pharmaceutical industry earning over $25 billion each year globally ( https://www. fiormarkets.com/report/global-proton-pump-inhibitor-drugmarket-research-report-54096.html ). Extessnsive randomized controlled trial data have shown these drugs are safe with adverse event rates very similar to placebo in the short term ( 1 ). Success stories in medicine oft en have a cycle of enthusiastic uptake followed by a period where caution is urged as reports regarding potential harm start to accrue. PPIs have been no exception to this phenomenon. Th e emergence of medical administrative databases such as the UK General Practice Research Database have allowed the evaluation of possible long term adverse eff ects of drugs using large numbers of patients with long term outcome data. Exploration of these databases suggested a link between PPIs and pneumonia ( 3 ) and this was soon followed by associations of PPI use and fracture ( 4 ), C. diffi cile risk ( 5 ), ischemic heart disease ( 6 ), chronic renal failure ( 7 ), and even all-cause mortality ( 8 ). Th e latest concern has been the association between PPI use and risk of dementia ( 9 ). A study ( 9 ) of 73,679 participants over the age of 75 yaers registered with a German statutory health insurer found regular PPI users had an increased risk of developing dementia with a hazard ratio of 1.44 (95% confi dence interval (CI) 1.36-0.152).It is important for others to replicate the association of PPIs with dementia as worldwide 47 million people have some form of dementia, a heterogeneous group of conditions which result in signifi cant decline in cognitive domains such as memory, executive function and social cognition ( 10 ). As the population ages, it is predicted that the number of people with dementia will increase to close...