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The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time\u2010varying exposure modeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40\u00a0years and older were classified as PPI initiators or non\u2010initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow\u2010up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1\u2010year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non\u2010initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time\u2010varying use versus non\u2010use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all, 29,746 PPI initiators (4.4%) and 26,830 non\u2010initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51\u20131.58). The hazard ratio for time\u2010dependent PPI use versus non\u2010use was 1.56 (95% confidence interval 1.50\u20131.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time\u2010varying PPI use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that PPI initiation and time\u2010varying PPI use may increase overall dementia risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15284","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T08:14:42Z","timestamp":1644999282000},"page":"1335-1343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Emulating a target trial of proton pump inhibitors and dementia risk using claims data"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4414-114X","authenticated-orcid":false,"given":"Nayeon","family":"Ahn","sequence":"first","affiliation":[{"name":"Institute for Medical Information Processing, 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