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Original Investigation |

Association of Proton Pump Inhibitors With Risk of Dementia A Pharmacoepidemiological Claims Data Analysis

Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1
[+] Author Affiliations
1German Center for Neurodegenerative Diseases, Bonn, Germany
2Federal Institute for Drugs and Medical Devices, Bonn, Germany
3Department of Psychiatry, University of Bonn, Bonn, Germany
4Rostock Center for the Study of Demographic Change, Rostock, Germany
5Max-Planck-Institute for Demographic Research, Rostock, Germany
6Institute for Sociology and Demography, University of Rostock, Rostock, Germany
JAMA Neurol. 2016;73(4):410-416. doi:10.1001/jamaneurol.2015.4791.
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Importance  Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective  To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Design, Setting, and Participants  We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.

Exposures  Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Main Outcomes and Measures  The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.

Results  A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

Conclusions and Relevance  The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

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Figure 1.
Flowchart of Patients Included for Analysis
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Figure 2.
Dementia-Free Survival by Use of Proton Pump Inhibitors (PPIs)
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Submit a Comment
Aluminum antacid use confounds this study
Posted on February 16, 2016
David Louis Keller, MD, FACP
Independent
Conflict of Interest: None Declared
Dietary aluminum ingestion is theorized to be neurotoxic and play a causative role in the onset and progression of dementia. A recent meta-analysis showed that individuals chronically exposed to aluminum were 71% more likely to develop AD (OR: 1.71, 95% confidence interval (CI), 1.35-2.18) [1]. Many strong antacids contain aluminum hydroxide, and are often taken for years by patients with peptic ulcer disease or gastro-esophageal reflux before they are prescribed proton pump inhibitors (PPIs), and concurrent with their use. Gomm and colleagues do not correct for the use of aluminum-containing antacids when calculating the association of dementia with PPI use. How much of their observed association of PPI use with dementia is actually due to chronic ingestion of aluminum antacids, either currently or in the past?

Reference

1: Wang Z, Wei X, Yang J, Suo J, Chen J, Liu X, Zhao X. Chronic exposure to
aluminum and risk of Alzheimer's disease: A meta-analysis. Neurosci Lett. 2016
Jan 1;610:200-6. doi: 10.1016/j.neulet.2015.11.014. Epub 2015 Nov 27. PubMed PMID: 26592479.
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