Adults with a recent history of clinically apparent Helicobacter pylori (HP) infection (CAHPI) have an increased risk for Alzheimer's disease (AD), compared with patients without CAHPI exposure, data suggested.
In a population-based cohort of 4,262,092 patients aged 50 years or older without dementia, CAHPI in the previous 2 years or more was associated with an 11% increased risk for AD compared with no exposure to CAHPI. A secondary analysis found a similarly increased risk for non-AD dementia with CAPHI exposure.
"Our result confirms the assumption that H pylori infection could be a modifiable risk factor for AD," senior author Paul Brassard, MD, a professor of medicine at McGill University in Montreal, told Medscape Medical News. "Whether and to what extent the consistent and comprehensive control of this stomach bacterium through so-called eradication programs actually influences the development of AD, however, must first be tested in large-scale, randomized trials."
The data were published on December 13 in Alzheimer's & Dementia.
Small Effect Size
The study cohort was taken from the UK Clinical Practice Research Datalink (CPRD) GOLD, a large primary care database covering more than 11 million patients at 674 UK general practices. Participants were enrolled between January 1988 and December 2017 and were followed until December 2019: Diagnosis of AD, end of registration with the CPRD's general practice, or death from any cause.
AD was defined as one or more of these criteria: AD diagnosis and one or more prescriptions for AD medications in any sequence, unspecified dementia diagnosis followed by two or more prescriptions for AD medications, two or more records of an AD diagnosis, AD diagnosis after a dementia test, and AD diagnosis and any dementia symptom (such as memory impairment, aphasia, apraxia, or agnosia). The investigators matched each AD case to as many as 40 AD-free controls selected from the same cohort with risk-set sampling.
They focused on patients with CAHPI who presented with symptoms or developed serious complications from the infection because "the majority of HP-infected individuals remain asymptomatic over time and may never develop any medical condition," the researchers wrote.
The definition of CAHPI was based on one or more of the following criteria: Positive urea breath test or monoclonal stool antigen test and eradication therapy within 30 days of the test, diagnosis of HP-related disease or related complication (such as uninvestigated or functional dyspepsia, unspecified gastric or duodenal ulcer, unspecified gastritis, or confirmed HP-gastritis) and eradication therapy within 30 days of the diagnosis, or diagnosis of gastric mucosa-associated lymphoid tissue lymphoma or noncardia gastric cancer.
The mean age of participants at cohort entry was 60.4 years, and 52.1% of the population were women. In all, 40,455 patients were diagnosed with AD. Compared with no exposure to CAHPI, exposure was associated with a "moderate but statistically significant" increase in the risk for AD (odds ratio [OR], 1.11), wrote the researchers. The increase in risk peaked at 7.3-10.8 years after CAHPI onset (OR, 1.24).
"Indeed, the effect size is small but significant and at the population level would not have a major impact taken alone," said Brassard. "We think it supports the infectious hypothesis in general as a potential contributor, through various mechanisms, to a neurodegenerative process."
A Chance Observation?
Commenting on the study for Medscape Medical News, David S. Knopman, MD, a clinical neurologist specializing in AD at the Mayo Clinic and professor of neurology at the Mayo Clinic College of Medicine, both in Rochester, Minnesota, said that he has concerns that such reports are "either of no use or actually misleading." Knopman did not participate in the research.
"First, the claim that they are looking at AD is simply a gross overstatement of diagnostic specificity. You can be certain that these administratively defined cases had dementia of diverse etiology," he told Medscape Medical News. "To make claims about risk for AD, where AD in this context actually meant all-cause dementia, is misleading."
Another concern "is that the likelihood that this is a chance observation that has no biological significance is very high, especially given the tiny effect size. Alternatively, it's possible that the association is real but entirely nonspecific. It is well known that there is a link between general health and risk of dementia, but in the end, a report like this just adds noise and confusion, not substance."
The study was funded by a project grant from the Canadian Institutes of Health Research. Brassard and another coauthor received consulting fees from Becton Dickinson and Pendopharm, respectively, on topics unrelated to this work. A coauthor attended scientific advisory committee meetings or consulted for AstraZeneca, Atara, Bristol-Myers-Squibb, Merck, Novartis, Panalgo, Pfizer, and Seqirus and received speaking fees from Boehringer-Ingelheim and Novartis. All other authors declared no conflict of interest. Knopman declared no conflicts of interest.
Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.
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