PMID- 37315867
OWN - NLM
STAT- MEDLINE
DCOM- 20230828
LR  - 20240410
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 165
IP  - 3
DP  - 2023 Sep
TI  - Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive 
      Decline in Older Adults: A Prospective Cohort Study.
PG  - 564-572.e1
LID - S0016-5085(23)00873-9 [pii]
LID - 10.1053/j.gastro.2023.05.052 [doi]
AB  - BACKGROUND & AIMS: Prior studies have suggested that proton pump inhibitor (PPI) 
      use is associated with increased risk of dementia; however, these have been 
      limited by incomplete assessment of medication use and failure to account for 
      confounders. Furthermore, prior studies have relied on claims-based diagnoses for 
      dementia, which can lead to misclassification. We investigated the associations 
      of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive 
      decline. METHODS: We conducted a post hoc analysis of ASPirin in Reducing Events 
      in the Elderly (ASPREE), a randomized trial of aspirin in the United States and 
      Australia, including 18,934 community-based adults >/=65 years of all 
      races/ethnicities. Baseline and recent PPI and H2RA use were determined according 
      to review of medications during annual in-person study visits. Incident dementia 
      was defined according to Diagnostic and Statistical Manual for Mental Disorders, 
      Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no 
      dementia (CIND) and changes in cognition. Associations of medication use with 
      dementia and CIND outcomes were examined using Cox proportional hazards models. 
      Changes in cognitive test scores were examined using linear mixed-effects models. 
      RESULTS: Baseline PPI use vs nonuse was not associated with incident dementia 
      (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND 
      (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with 
      changes in overall cognitive test scores over time (multivariable B, -0.002; 
      standard error, 0.01; P = .85). Similarly, no associations were observed between 
      H2RA use and all cognitive endpoints. CONCLUSIONS: In adults >/=65 years of age, 
      PPI and H2RA use were not associated with incident dementia, CIND, or decline in 
      cognition over time. These data provide reassurance about the safety of long-term 
      use of PPIs among older adults.
CI  - Copyright (c) 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Mehta, Raaj S
AU  - Mehta RS
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts.
FAU - Kochar, Bharati
AU  - Kochar B
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts.
FAU - Zhou, Zhen
AU  - Zhou Z
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, 
      Australia.
FAU - Broder, Jonathan C
AU  - Broder JC
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Chung, Paget
AU  - Chung P
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts.
FAU - Yang, Keming
AU  - Yang K
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts.
FAU - Lockery, Jessica
AU  - Lockery J
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Fravel, Michelle
AU  - Fravel M
AD  - Department of Pharmacy Practice and Science, College of Pharmacy, University of 
      Iowa, Iowa City, Iowa; Department of Family Medicine, Carver College of Medicine, 
      University of Iowa, Iowa City, Iowa.
FAU - Ryan, Joanne
AU  - Ryan J
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Mahady, Suzanne
AU  - Mahady S
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Orchard, Suzanne G
AU  - Orchard SG
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - McNeil, John J
AU  - McNeil JJ
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Murray, Anne
AU  - Murray A
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Woods, Robyn L
AU  - Woods RL
AD  - School of Public Health and Preventive Medicine, Monash University, Melbourne, 
      Australia.
FAU - Ernst, Michael E
AU  - Ernst ME
AD  - Department of Pharmacy Practice and Science, College of Pharmacy, University of 
      Iowa, Iowa City, Iowa; Department of Family Medicine, Carver College of Medicine, 
      University of Iowa, Iowa City, Iowa.
FAU - Chan, Andrew T
AU  - Chan AT
AD  - Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and 
      Harvard Medical School, Boston, Massachusetts; Channing Division of Network 
      Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 
      Massachusetts. Electronic address: achan@mgh.harvard.edu.
LA  - eng
GR  - P30 AG024824/AG/NIA NIH HHS/United States
GR  - RF1 AG067744/AG/NIA NIH HHS/United States
GR  - U01 AG029824/AG/NIA NIH HHS/United States
GR  - U19 AG062682/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230612
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - R16CO5Y76E (Aspirin)
RN  - 0 (Proton Pump Inhibitors)
SB  - IM
MH  - Aged
MH  - Humans
MH  - Aspirin
MH  - Cognition
MH  - *Cognitive Dysfunction/diagnosis/epidemiology
MH  - Prospective Studies
MH  - *Proton Pump Inhibitors/adverse effects
MH  - Risk Factors
MH  - United States/epidemiology
PMC - PMC10527011
MID - NIHMS1909200
OTO - NOTNLM
OT  - Cognition
OT  - Dementia
OT  - Pharmacoepidemiology
OT  - Proton Pump Inhibitors
COIS- Conflict of interest: Dr Chan served as a consultant for Bayer Pharma AG, Pfizer 
      Inc., and Boehringer Ingelheim. Dr. Kochar served on an advisory board to Pfizer. 
      This study was not funded by Bayer Pharma AG, Boehringer Ingelheim, or Pfizer 
      Inc. No other conflict of interest exists. The other authors declare that they 
      have no conflicts of interest.
EDAT- 2023/06/15 01:08
MHDA- 2023/08/22 06:42
PMCR- 2024/09/01
CRDT- 2023/06/14 19:18
PHST- 2023/03/16 00:00 [received]
PHST- 2023/05/02 00:00 [revised]
PHST- 2023/05/12 00:00 [accepted]
PHST- 2024/09/01 00:00 [pmc-release]
PHST- 2023/08/22 06:42 [medline]
PHST- 2023/06/15 01:08 [pubmed]
PHST- 2023/06/14 19:18 [entrez]
AID - S0016-5085(23)00873-9 [pii]
AID - 10.1053/j.gastro.2023.05.052 [doi]
PST - ppublish
SO  - Gastroenterology. 2023 Sep;165(3):564-572.e1. doi: 10.1053/j.gastro.2023.05.052. 
      Epub 2023 Jun 12.