Another large study has found a link between proton pump inhibitors (PPIs) and an increased risk of dementia, particularly among people aged 60-69. But scientists still don't fully understand why. The conclusions drawn by researchers at Copenhagen University Hospital and Aarhus University in Denmark support earlier studies that found a link between stomach acid inhibitors and cognitive decline.
The extensive Danish study examined medical data from 1,983,785 residents aged 60 to 75 who regularly used PPIs between 2000 and 2018. During this period, 99,384 people developed dementia. The data set was compared to a control group of 469,920 people who had never used PPIs.
Overall, patients who used PPIs and were 60 to 69 years old at the time of dementia diagnosis had an incidence rate ratio of 1.25 to 1.59, with risk varying with length of use, compared with an incidence rate ratio of 1.36 for the control group. However, the older you are, the smaller the risk association. Compared with the control group, the dementia incidence rate increased slightly (1.12) in those aged 70-79 years, while the incidence rate was lower at 1.06 in those aged 80-89 years.
The researchers noted in the study: "PPIs can pass the blood-brain barrier, and their use has been associated with neurological adverse effects, such as migraine, peripheral neuropathy, hearing, vision, and memory impairment. A recent study showed that PPIs can effectively and selectively inhibit the enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine (choline acetyltransferase), thereby potentially inhibiting neuronal signaling in the brain."
Although PPIs inhibit gastric acid secretion, how they affect brain function remains unclear. The scientists noted that reverse causation may also exist, with increased gastric acid secretion in the early stages of dementia.
PPIs are commonly used to treat conditions such as peptic ulcers and gastroesophageal reflux disease (GER), and the number of adults over 40 years old taking them has increased worldwide over the past 20 years.
"The association between PPI use and dementia was undoubtedly greatest among the youngest cases of dementia, which may indicate the existence of a critical window of exposure in which PPI use in midlife affects dementia risk to a greater extent than PPI use in later life," the researchers said.
The scientists noted that while the study had limitations, they said the broad study highlighted the vulnerability of certain age groups, which is important for future research and potential medical interventions for those most at risk.
They added: "Further research is necessary to determine whether these findings represent a causal effect of PPIs on dementia risk."
The research was published in the journal Alzheimer's Association.