Another large study has found a correlation between proton pump inhibitors (PPI) and an increased risk of dementia, particularly for those aged 60-69 years. But scientists still don’t fully understand why.
The findings from researchers from Copenhagen University Hospital and Aarhus University in Denmark support earlier studies that have found a link between the stomach acid suppressors and cognitive decline. The broad Danish study examined medical data from 1,983,785 residents aged 60 to 75 regularly using PPIs, between 2000 and 2018. During the time frame, 99,384 people in this cohort developed dementia. This dataset was measured against a control group of 469,920 who had never used a PPI.
Overall, those who used PPIs and were aged 60-69 at the time of their dementia diagnosis had an incidence rate ratio of 1.25 to 1.59, with the risk changing based on how long the medication was used, compared to a ratio rate of 1.36 for the control cohort. However, those in older age brackets had increasingly less significant risk correlation. People aged 70-79 had a slightly elevated dementia prevalence (1.12) compared to the control cohort, and those aged 80-89, lower still at 1.06.
“PPIs pass through the blood-brain barrier and their use has been associated with neurological adverse reactions such as migraine, peripheral neuropathies, and impairment of hearing, vision, and memory,” the researchers note in the research. “A recent study showed that PPIs potently and selectively inhibit the enzyme responsible for biosynthesis of the neurotransmitter acetylcholine (choline-acetyltransferase), and thereby may inhibit neuronal signaling in the brain.”
While PPIs act to suppress gastiric-acid production, just how they’re impacting brain function remains unclear. The scientists note that there could also be a reverse causality at play, with acid production in the stomach ramping up in the early stages of dementia.
The worldwide uptake of PPIs, which are commonly used to treat conditions such as peptic ulcers and gastroesophageal reflux disease (GER), has increased in the last 20 years among adults over 40.
“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the researchers said.
The scientists, who note that while the study has limitations, say the extensive study highlighting vulnerabilities in certain age groups is important for future research and potential medical intervention for those most at risk.
“Further studies are warranted to determine if these findings represent a causal effect of PPIs on dementia risk,” they added, noting how understanding the mechanism linking the brain and gut in this instance is crucial.
The research was published in the journal Alzheimer’s Association.
Source: Aarhus University via MedicalXpress
