Many older adults take proton pump inhibitors (PPIs) to treat gastrointestinal diseases. And, many older adults have dementia. Recently, a study in JAMA Neurology linked these two common features of the elderly, but questions remain about the validity of the results and about the real risk of PPI use.

The authors of the current study examined eight years of German data and evaluated associations between PPI use and new diagnoses of dementia. They report that the nearly 3,000 people who were older than 75 and regularly used PPIs had a significantly increased risk of developing dementia compared to people who did not regularly use PPIs. (The same group published a similar report of a longitudinal multicenter study in the European Archives of Psychiatry and Clinical Neuroscience; both studies reported an approximately 1.4-fold increased risk of developing dementia with regular PPI use.) The authors go so far as to posit that avoiding PPIs may prevent dementia.

This observed association between PPIs and dementia is supported by previous pharmacoepidemiological studies and mouse models that indicate that PPI use alters the development and metabolism of beta-amyloid plaques, a key factor in Alzheimer’s, a specific type of dementia. Still, many other factors contribute to the development of dementia, and the authors of the current study adjusted the estimated risks of dementia for several confounding factors: age, sex, other medications, history of stroke, depression, diabetes, and ischemic heart disease. But, they did not adjust for other well-known risks such as family history of dementia, hypertension, and alcohol use. Further, they did not address length of PPI use or dose in the association with dementia.

Data are unclear and associations are far from conclusive evidence of cause-and-effect. In fact, a recent case-control study (also conducted in Germany) reported that PPIs were associated with a decreased risk of dementia. And, several reports of medication use in older adults add to the “which comes first” conundrum of PPIs and dementia. In fact, the reports claim that dementia is associated with an increased risk of inappropriate PPI use.

By 2040, nearly 100 million people worldwide are expected to suffer from dementia. So, an increased understanding of the risks associated with this condition is warranted. However, the current study leaves too many questions unanswered to claim that PPI use should be avoided in the elderly.

Still, the findings may serve as a reminder that many medicines are prescribed incorrectly or inappropriately – especially in the elderly – and health care providers should be diligent to ensure that all medications are used only for the correct indications and at the correct doses, while minimizing risks associated with all medication use.

References

Badiola N, Alcalde V, Pujol A, Münter LM, Multhaup G, Lleó A, Coma M, Soler-López M, & Aloy P (2013). The proton-pump inhibitor lansoprazole enhances amyloid beta production. PloS one, 8 (3) PMID: 23520537

Booker A, Jacob LE, Rapp M, Bohlken J, & Kostev K (2016). Risk factors for dementia diagnosis in German primary care practices. International psychogeriatrics / IPA, 1-7 PMID: 26744954

Dwyer LL, Lau DT, & Shega JW (2015). Medications That Older Adults in Hospice Care in the United States Take, 2007. Journal of the American Geriatrics Society, 63 (11), 2282-9 PMID: 26531894

Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, Doblhammer G, & Haenisch B (2016). Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA neurology PMID: 26882076

Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, Brettschneider C, König HH, Werle J, Weyerer S, Luppa M, Riedel-Heller SG, Fuchs A, Pentzek M, Weeg D, Bickel H, Broich K, Jessen F, Maier W, & Scherer M (2015). Risk of dementia in elderly patients with the use of proton pump inhibitors. European archives of psychiatry and clinical neuroscience, 265 (5), 419-28 PMID: 25341874

Hamzat H, Sun H, Ford JC, Macleod J, Soiza RL, & Mangoni AA (2012). Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs & aging, 29 (8), 681-90 PMID: 22775478

Parsons C, Johnston S, Mathie E, Baron N, Machen I, Amador S, & Goodman C (2012). Potentially inappropriate prescribing in older people with dementia in care homes: a retrospective analysis. Drugs & aging, 29 (2), 143-55 PMID: 22204669

Image via Lucky Business / Shutterstock.