H. pylori Infection – A Potential Modifiable Risk Factor of Alzheimer’s Dementia

By Seema Gupta, MD, MSPH

Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV

SYNOPSIS: A large nested case-control cohort study of subjects aged 50 years and older found that clinically apparent Helicobacter pylori infection is associated with a moderately increased risk of developing Alzheimer’s disease.

SOURCE: Douros A, Ante Z, Fallone CA, et al. Clinically apparent Helicobacter pylori infection and the risk of incident Alzheimer’s disease: A population-based nested case-control study. Alzheimers Dement 2023; Dec 13. doi: 10.1002/alz.13561. [Online ahead of print.]

It is estimated that 6.7 million (10.7%) people aged 65 years and older in the United States are living with Alzheimer’s dementia (AD). The number could double in the next three decades unless there is a breakthrough to prevent, cure, or slow down the disease.¹ Although mortality from leading causes of death like heart disease has declined, deaths from AD more than doubled between 2000 and 2019. Not only is AD an expensive disease to manage, but it takes a devastating toll on caregivers.

AD is a multifactorial disease affected by genetic and environmental factors. Recent reports have suggested that microorganisms, including various bacteria, viruses, and even some parasites, may trigger pathological changes in the brain that may induce accumulation of beta-amyloid aggregates.² Specifically, studies have demonstrated an association between AD and infectious pathogens like Helicobacter pylori.³ There have been suggestions that the mere presence of infectious agents may induce both local and systemic inflammatory responses promoting cellular damage and neuronal loss. However, several of the previous studies suffered from methodological limitations that made it difficult to clearly interpret their findings.

To more definitively understand the public health effect of whether pathogens like H. pylori are associated with an increased risk of AD, Douros et al studied a population-based cohort of more than 4 million dementia-free subjects aged 50 years or older in the United Kingdom between 1988 and 2017 and followed the subjects until 2019. The researchers used a nested case-control approach within the cohort so that each newly diagnosed case of AD was matched with 40 randomly selected controls (not having AD).

The exposure of interest was clinically apparent H. pylori infection (CAHPI), defined based on an algorithm using clinical guidelines and recommendations on the management of H. pylori infection. Because individuals with H. pylori can remain asymptomatic over time and may never develop any medical condition, researchers focused on infected subjects presenting with symptoms or developing serious complications from the infection.

Douros et al found that, compared to no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.01-1.21), with no major effect modification by demographics or socioeconomic status. This elevated risk peaked at 7.3 to 10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before declining. The authors concluded that CAHPI was associated with a moderately increased risk of AD.

COMMENTARY

According to the Alzheimer’s Association, AD and other dementias cost the nation $345 billion, which does not include the significant costs of unpaid caregiving. Medicare and Medicaid were expected to cover $222 billion (64%), while out-of-pocket spending was expected to be $87 billion.¹ It also is estimated that the total payments for healthcare, long-term care, and hospice care for people living with dementia are projected to increase to nearly $1 trillion in 2050. The total lifetime cost of care for a single person in the United States living with dementia is estimated at $392,874.

The Douros et al findings of a moderate but statistically significant increase (11%) in the risk of AD associated with CAHPI in subjects aged ≥ 50 years is important for several reasons. First, a large sample size, sound methodology, and the decades-long follow-up represented in this study are critical to ascertaining accurate estimates of the association between CAHPI and AD risk. Second, these results point to symptomatic H. pylori infection as a potential modifiable risk factor of AD. Thus, there is a need to understand whether efforts to eradicate H. pylori may actually affect the development of AD and/or other dementias and, if so, to what extent. Third, this study more definitively indicates that systemic infections potentially can cause inflammation, damage, and the destruction of neurons in the brain. And finally, serious consideration should be given to adding AD prevention as a part of H. pylori intervention and surveillance programs across the globe that already are being tested for gastric cancer prevention. Treatment for H. pylori may become a future public health approach to preventing AD and related dementias, similar to other modifiable risk factors such as physical activity, smoking prevention, weight management, chronic disease management, and others.⁴

REFERENCES

1. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement 2023;19:1598-1695.
2. Piekut T, Hurla M, Banaszek N, et al. Infectious agents and Alzheimer’s disease. J Integr Neurosci 2022;21:73.
3. Noori M, Mahboobi R, Nabavi-Rad A, et al. Helicobacter pylori infection contributes to the expression of Alzheimer’s disease-associated risk factors and neuroinflammation. Heliyon 2023;9:e19607.
4. Omura JD, McGuire LC, Patel R, et al. Modifiable risk factors for Alzheimer disease and related dementias among adults aged ≥ 45 years — United States, 2019. MMWR Morb Mortal Wkly Rep 2022;71:680-685.