Proton Pump Inhibitors Linked to Dementia in the Elderly

In the previous issue of Worst Pills, Best Pills News, we discussed the increased risk of chronic kidney disease associated with proton pump inhibitors (PPIs).[1] These medications (including esomeprazole [NEXIUM], omeprazole [PRILOSEC] and pantoprazole [PROTONIX]) are widely used, especially among the elderly, to treat acid-related disorders of the upper gastrointestinal tract, including heartburn and peptic ulcers.[2]

We previously have classified all PPIs as Limited Use drugs, due to their long list of serious side effects.[3]

A recent German study offers evidence for yet another potential serious side effect for PPIs. Specifically, the study linked these drugs to an increased risk of dementia, a disorder that is common among the elderly and is characterized by gradual deterioration in cognitive ability and capacity to live independently.

The new study

The study was published in the April issue of the Journal of the American Medical Association (JAMA) Neurology.[4] It used data from a medical insurance database made up of claims from 2004 to 2011, representing about half of Germany’s elderly population. The researchers examined data pertaining to patients 75 years of age or older who did not have dementia at baseline.

From those patients, the researchers further selected two groups: regular PPI users (with at least one PPI prescription every three months for a total of 18 months) and non-users (with no PPI prescriptions for the same period). The number of regular PPI users included in the study was nearly 3,000, and the number of non-users was about 71,000. Three-quarters of the patients were female, with an average age of 83.

Comparing the two groups, the researchers found a 44 percent increased risk of a new dementia diagnosis among regular PPI users, compared with non-users. A subgroup analysis of the three most commonly used PPIs (omeprazole, pantoprazole and esomeprazole) showed similar associations, with a slightly more pronounced risk among esomeprazole users. The researchers adjusted their analysis for several factors that might bias the results, such as age, sex, existing health conditions and simultaneous use of multiple drugs.

The findings of the new study are consistent with those from a similar but smaller 2015 study, also conducted in Germany.[5] The 2015 study, involving over 3,300 adults ages 75 and older, linked PPI use to a 38 percent increased risk of dementia compared to non-users.

These two studies do not establish a direct cause-and-effect relationship between PPI use and dementia. Yet further support for the strong associations found in these studies comes from animal studies showing that PPIs can affect certain chemicals in the brain that may play a role in the development of dementia.[6] Additional research points to reduced levels of vitamin B12 in PPI users, which, in turn, may lead to cognitive decline.[7]

Even a small risk increase matters

In an editorial accompanying the JAMA Neurology study,[8] Dr. Lewis Kuller from the University of Pittsburgh emphasized the importance of the study findings considering the widespread long-term use of PPIs in the elderly, who already have a very high risk of dementia.

Kuller cautioned that even a relatively small increased risk of dementia can translate into many more people with this condition. Using estimates from the new study, along with prior estimates that about 3 percent of the elderly population receive long-term PPI therapy, he estimated that PPI use in patients age 75 to 84 could lead to approximately 10,000 additional cases of dementia each year in the U.S.

What You Can Do

If you suffer from heartburn, you should first try nondrug approaches to relieve your symptoms. Raising the head of the bed at night and avoiding excessive amounts of alcohol, coffee, chocolate or foods high in fat, for example, can go a long way toward relieving heartburn symptoms.

If you require medications, we recommend that you first try over-the-counter antacids unless you have kidney disease, in which case you should first check with your health care provider. If antacids do not work, you can try histamine-2-receptor antagonists (H2As), such as famotidine (PEPCID) or ranitidine (ZANTAC). H2As are a safer alternative with fewer side effects than PPIs.

If nondrug approaches or H2A drugs fail to relieve your gastrointestinal symptoms, you may ask your health care provider for the lowest effective dose of a PPI for the shortest time possible.

Discuss the risks of PPIs with your health care provider. For a detailed discussion of these risks, see our related article in the November 2011 issue of Worst Pills, Best Pills News.[9]

If you are taking PPIs, watch for early signs of dementia (including changes in memory or thinking abilities), in which case these medications need to be discontinued under medical supervision.

References

[1] Proton pump inhibitors might cause chronic kidney disease. Worst Pills, Best Pills News. July 2016. /newsletters/view/1041. Accessed July 11, 2016.

[2] Maggio M, Corsonello A. Use of proton pump inhibitors in older subjects: Risk of adverse clinical outcomes and potential mechanisms. Eur Geriatr Med. 2015;6(1):94-95.

[3] WorstPills.org. Drug profile: Proton pump inhibitors. /monographs/view/239. Accessed May 11, 2016.

[4] Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.

[5] Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-428.

[6] Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.

[7] Ibid.

[8] Kuller LH. Do proton pump inhibitors increase the risk of dementia? JAMA Neurol. 2016;73(4):379-381.

[9] Proton pump inhibitors: Dangerous and habit-forming heartburn drugs. Worst Pills, Best Pills News. November 2011. /newsletters/view/772. Accessed May 11, 2016.