PMID- 36260313
OWN - NLM
STAT- MEDLINE
DCOM- 20221223
LR  - 20230209
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 113
IP  - 1
DP  - 2023 Jan
TI  - Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?
PG  - 152-159
LID - 10.1002/cpt.2767 [doi]
AB  - The association between proton pump inhibitor (PPI) use and dementia remains 
      controversial. This cohort study re-examines this issue, addressing shortcomings 
      identified in previous publications using a population-based and a high-dimension 
      propensity-score matched cohort to follow patients for up to 22 years. Cox 
      regression models using baseline characteristics, a lag period, and time-varying 
      variables were used to examine the risk of dementia by cumulative PPI exposure. 
      High-dose PPI users (> 180 days of use) had significantly higher risk of dementia 
      in crude Cox models. After adjustment for medical diagnoses and prescription drug 
      use, these associations disappeared. Among high-dose users starting PPI therapy 
      between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% 
      confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 
      (95% CI 0.80, 1.51). For high-dose users starting therapy between 56 and 
      65 years, HR = 1.22 (95% CI1.03, 1.44); aHR = 0.99 (95% CI 0.83, 1.17). High-dose 
      users between the ages of 66 and 75 years had no association with the risk of 
      dementia. The use of lag models or time-varying parameters similarly found some 
      association with dementia in crude, but not multivariable Cox models. Although 
      high-dose PPI users were more likely to develop dementia, they were more likely 
      to be diagnosed with dementia risk factors, such as diabetes and cardiovascular 
      disease, which are risk factors for dementia. Controlling for these conditions 
      using multivariable models or a propensity-score matched cohort eliminated this 
      association.
CI  - (c) 2022 The Authors. Clinical Pharmacology & Therapeutics (c) 2022 American Society 
      for Clinical Pharmacology and Therapeutics.
FAU - Friesen, Kevin J
AU  - Friesen KJ
AUID- ORCID: 0000-0002-6038-550X
AD  - College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 
      Winnipeg, Manitoba, Canada.
FAU - Falk, Jamie
AU  - Falk J
AUID- ORCID: 0000-0003-4029-320X
AD  - College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 
      Winnipeg, Manitoba, Canada.
FAU - Chateau, Dan
AU  - Chateau D
AUID- ORCID: 0000-0002-2215-820X
AD  - Research School of Population Health, ANU College of Health and Medicine, 
      Australian National University, Canberra, Australian Capital Territory, 
      Australia.
FAU - Kuo, I Fan
AU  - Kuo IF
AUID- ORCID: 0000-0002-2660-2777
AD  - Optimal Use and Evaluation, Clinical Services and Evaluation Branch, 
      Pharmaceutical, Laboratory & Blood Services, British Columbia Ministry of Health, 
      Victoria, British Columbia, Canada.
FAU - Bugden, Shawn
AU  - Bugden S
AUID- ORCID: 0000-0002-9842-5909
AD  - College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 
      Winnipeg, Manitoba, Canada.
AD  - School of Pharmacy, Memorial University of Newfoundland, St. John's, 
      Newfoundland, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221108
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Proton Pump Inhibitors)
SB  - IM
MH  - Humans
MH  - Aged
MH  - Middle Aged
MH  - Cohort Studies
MH  - Proton Pump Inhibitors
MH  - Risk Factors
MH  - *Cardiovascular Diseases/drug therapy
MH  - *Dementia/chemically induced/diagnosis/epidemiology
EDAT- 2022/10/20 06:00
MHDA- 2022/12/24 06:00
CRDT- 2022/10/19 11:33
PHST- 2022/07/05 00:00 [received]
PHST- 2022/10/03 00:00 [accepted]
PHST- 2022/10/20 06:00 [pubmed]
PHST- 2022/12/24 06:00 [medline]
PHST- 2022/10/19 11:33 [entrez]
AID - 10.1002/cpt.2767 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2023 Jan;113(1):152-159. doi: 10.1002/cpt.2767. Epub 2022 
      Nov 8.