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. 2023 Oct 31;101(18):e1771-e1778.
doi: 10.1212/WNL.0000000000207747. Epub 2023 Aug 9.

Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study

Carin A Northuis  1 , Elizabeth J Bell  1 , Pamela L Lutsey  1 , Kristen M George  1 , Rebecca F Gottesman  1 , Tom H Mosley  1 , Eric A Whitsel  1 , Kamakshi Lakshminarayan  2
Affiliations

Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study

Carin A Northuis et al. Neurology. .

Erratum in

  • Corrections to Received Date Information.
    [No authors listed] [No authors listed] Neurology. 2024 Jul 9;103(1):e209596. doi: 10.1212/WNL.0000000000209596. Epub 2024 Jun 3. Neurology. 2024. PMID: 38830175 Free PMC article. No abstract available.

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.

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Conflict of interest statement

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.

Figures

Figure
Figure. Flowchart of Participants in the Atherosclerosis Risk in Communities Study, 2011–2017
APOE4 = Apolipoprotein E4; BMI = body mass index.
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