PMID- 37558503 OWN - NLM STAT- MEDLINE DCOM- 20231101 LR - 20240425 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 101 IP - 18 DP - 2023 Oct 31 TI - Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. PG - e1771-e1778 LID - 10.1212/WNL.0000000000207747 [doi] AB - BACKGROUND AND OBJECTIVES: Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use. We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: These analyses used participants from a community-based cohort (ARIC) from the time of enrollment (1987-1989) through 2017. PPI use was assessed through visual medication inventory at clinic visits 1 (1987-1989) to 5 (2011-2013) and reported annually in study phone calls (2006-2011). This study uses ARIC visit 5 as baseline because this was the first visit in which PPI use was common. PPI use was examined 2 ways: current use at visit 5 and duration of use before visit 5 (from visit 1 to 2011, exposure categories: 0 day, 1 day-2.8 years, 2.8-4.4 years, >4.4 years). The outcome was incident dementia after visit 5. Cox proportional hazard models were used, adjusted for demographics, comorbid conditions, and other medication use. RESULTS: A total of 5,712 dementia-free participants at visit 5 (mean age 75.4 +/- 5.1 years; 22% Black race; 58% female) were included in our analysis. The median follow-up was 5.5 years. The minimum cumulative PPI use was 112 days, and the maximum use was 20.3 years. There were 585 cases of incident dementia identified during follow-up. Participants using PPIs at visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs (hazard ratio (HR): 1.1 [95% confidence interval (CI) 0.9-1.3]). Those who used PPIs for >4.4 cumulative years before visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3 [95% CI 1.0-1.8]) than those reporting no use. Associations were not significant for lesser durations of PPI use. DISCUSSION: Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia. CI - Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government. FAU - Northuis, Carin A AU - Northuis CA AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Bell, Elizabeth J AU - Bell EJ AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Lutsey, Pamela L AU - Lutsey PL AUID- ORCID: 0000-0002-1572-1340 AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - George, Kristen M AU - George KM AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Gottesman, Rebecca F AU - Gottesman RF AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Mosley, Tom H AU - Mosley TH AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Whitsel, Eric A AU - Whitsel EA AUID- ORCID: 0000-0003-4843-3641 AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. FAU - Lakshminarayan, Kamakshi AU - Lakshminarayan K AD - From the University of Minnesota (C.A.N., P.L.L., K.L.), Minneapolis; Optum (E.J.B.), Minneapolis, MN; University of California, Davis (K.M.G.); National Institute of Neurological Disorders and Stroke (R.F.G.), Washington, DC; University of Mississippi Medical Center (T.H.M.), Jackson; and University of North Carolina (E.A.W.), Chapel Hill. laksh004@umn.edu. LA - eng GR - T32 HL007779/HL/NHLBI NIH HHS/United States GR - 75N92022D00002/HL/NHLBI NIH HHS/United States GR - U01 HL096902/HL/NHLBI NIH HHS/United States GR - U01 HL096899/HL/NHLBI NIH HHS/United States GR - 75N92022D00005/HL/NHLBI NIH HHS/United States GR - U01 HL096917/HL/NHLBI NIH HHS/United States GR - K24 AG078506/AG/NIA NIH HHS/United States GR - 75N92022D00003/HL/NHLBI NIH HHS/United States GR - K24 HL159246/HL/NHLBI NIH HHS/United States GR - 75N92022D00004/HL/NHLBI NIH HHS/United States GR - U01 HL096812/HL/NHLBI NIH HHS/United States GR - 75N92022D00001/HL/NHLBI NIH HHS/United States GR - U01 HL096814/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230809 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Proton Pump Inhibitors) SB - IM CIN - MMW Fortschr Med. 2024 Mar;166(4):35. PMID: 38453855 MH - Humans MH - Female MH - Aged MH - Aged, 80 and over MH - Male MH - *Dementia/chemically induced/epidemiology/drug therapy MH - Proton Pump Inhibitors/adverse effects MH - Risk Factors MH - *Atherosclerosis/chemically induced/epidemiology/drug therapy MH - Black People PMC - PMC10634644 COIS- C.A. Northuis reports no disclosures relevant to the manuscript; E.J. Bell is employed by Optum, and she has received funding Novartis, Incyte, AstraZeneca, EMD Serono, Sandoz, Celgene, and Pfizer; P.L. Lutsey receives NIH funding; K.M. George reports no disclosures relevant to the manuscript; R.F. Gottesman is supported by the NIH intramural program; T.H. Mosley receives NIH funding; E.A. Whitsel reports no disclosures relevant to the manuscript; K. Lakshminarayan receives NIH funding. Go to Neurology.org/N for full disclosures. EDAT- 2023/08/10 00:42 MHDA- 2023/11/01 12:44 PMCR- 2024/10/31 CRDT- 2023/08/09 21:37 PHST- 2023/05/04 00:00 [received] PHST- 2023/06/20 00:00 [accepted] PHST- 2024/10/31 00:00 [pmc-release] PHST- 2023/11/01 12:44 [medline] PHST- 2023/08/10 00:42 [pubmed] PHST- 2023/08/09 21:37 [entrez] AID - WNL.0000000000207747 [pii] AID - WNL-2023-001702 [pii] AID - 10.1212/WNL.0000000000207747 [doi] PST - ppublish SO - Neurology. 2023 Oct 31;101(18):e1771-e1778. doi: 10.1212/WNL.0000000000207747. Epub 2023 Aug 9.