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Abstract
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.
Glossary
- ARIC=
- Atherosclerosis Risk in Communities;
- BMI=
- body mass index;
- CKD=
- chronic kidney disease;
- GERD=
- gastroesophageal reflux disease;
- H2RAs=
- Histamine2 receptor antagonists;
- HR=
- hazard ratio;
- NHLBI=
- National Heart, Lung, and Blood Institute;
- PPIs=
- proton pump inhibitors
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
K. Lakshminarayan is senior author.
Submitted and externally peer reviewed. The handling editor was Associate Editor Linda Hershey, MD, PhD, FAAN.
Class of Evidence: NPub.org/coe
- Received May 4, 2023.
- Accepted in final form June 20, 2023.
- 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.
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- Author Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
- Author Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
- Author Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
- Reader Response: Cumulative use of proton pump inhibitors and risk of dementia: The Atherosclerosis Risk in Communities Study
- Reader Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
- Reader Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia
- Reader Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
- Reader Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.
- Reader Response: Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study
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