Piling on PPIs -Now Concerns about Dementia

A recent study (see abstract below -from Mike Hart) indicates the possibility that proton pump inhibitors (PPIs) could increase the risk of dementia to a small degree.  Despite the big numbers, this study cannot adequately control for numerous factors that could influence these results.  As is often said, association does not prove causation.  Nevertheless, this study is another reminder to use PPIs when indicated and to use them for the appropriate length of therapy.

Here’s NBC News Narrative: Popular Heartburn Drugs Linked to Dementia

ONLINE FIRST

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

JAMA Neurol
. Published online February 15, 2016. doi:10.1001/jamaneurol.2015.4791
 
ABSTRACT

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.

Related blog post: Proton Pump Inhibitors Webinar

Unrelated article (from Ben Gold): J Molina-Infante et al. Am J Gastroenterol 2015; 110: 1567-1575.  This study examined 75 patients (mean age 38 years) with proton-pump inhibitor responsive esophageal eosinophilia (PPI-REE).  55 (73%) had long-term sustained histologic remission with low-dose PPI therapy (20 mg once or twice daily). In addition, the article noted that 9 of 10 relapsers with distal eosinophilia were noted to have a CYP2C19 rapid metabolizer genotype and regained histologic remission with dose intensification.

Briefly noted: AI Sharara et al. Clin Gastroenterol Hepatol 2016; 14: 317-21.  Among 414 who met inclusion criteria (at least 6 months of PPI usage and at least 1 serum magnesium level), 57 (13.8%) had at least 1 low serum magnesium –44 of these patients had recognizable causes (eg. diuretics, chronic diarrhea).  Of the remainder who continued with PPI therapy, the level was normal at final measurement and only mildly low levels were noted previously.  Thus, in patients without other reasons for low magnesium, the authors found that use of a PPI does not appear to be associated with hypomagnesemia.

 

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