Alzheimer’s disease (AD), a prevalent form of dementia affecting approximately 40 million people worldwide, has been the focus of extensive research aiming to unravel its complex etiology. Recent studies have begun exploring an intriguing ‘infectious hypothesis,’ suggesting that various pathogens, including Helicobacter pylori (HP), might significantly influence AD’s development.
This hypothesis, initially grounded in pre-clinical, serological, and post-mortem studies, has gained traction through observational studies linking infectious disease burden to an elevated risk of AD.
A pivotal population-based study by our group revealed a subtle yet statistically significant correlation between infections associated with AD pathophysiology and an increased risk of this neurodegenerative disease. Interestingly, this study highlighted a specific association with clinically detected, unspecified gastritis, aligning with prior research suggesting a link between HP infection and a heightened risk of AD.
However, these findings must be viewed cautiously due to potential methodological flaws, such as reverse causality and detection bias in previous studies, alongside inconsistent results across different research.
In light of these limitations, our team embarked on a comprehensive population-based study, focusing on individuals aged 50 and above, to more accurately determine the relationship between clinically apparent HP infection (CAHPI) and the risk of AD. This systematic approach involved reviewing existing literature through databases like PubMed, noting the methodological challenges in earlier studies that made their conclusions less reliable.
Our large-scale study revealed a notable 11% increase in AD risk among subjects aged 50 or older, exposed to CAHPI. This risk peaked at 24% about ten years after the onset of CAHPI, with no significant demographic variations. Multiple sensitivity analyses reinforced these primary findings, underscoring the potential role of HP infection as a modifiable risk factor for AD.
The proposed mechanisms linking HP to AD are multifaceted. HP may access the brain through various routes, including the oral-nasal-olfactory axis or infected circulating monocytes, potentially leading to neuroinflammation and neurodegeneration. Disruption of the gut-brain axis due to HP infection could activate pathological pathways, including amyloid and lipopolysaccharide oversecretion, pro-inflammatory cytokine production, and alterations in gut and blood-brain-barrier permeability. Additionally, chronic HP infection could impair the absorption of vital nutrients like vitamin B12 and iron, deficiencies of which are linked to dementia.
Our study’s strengths lie in its large sample size, extensive follow-up period, and methodological rigor, including the use of a lag period to minimize biases present in earlier studies. However, it’s important to acknowledge its observational nature, which leaves room for residual confounding despite adjustments for various potential confounders. Additionally, misclassification of exposure and outcome cannot be entirely ruled out.
In conclusion, our research contributes significantly to the understanding of AD, suggesting a moderate increase in AD risk associated with CAHPI in individuals over 50 years. These insights bolster the concept of HP infection as a potentially modifiable risk factor for AD and lay the groundwork for future randomized trials. Such trials could evaluate the impact and cost-effectiveness of targeted interventions like individualized HP eradication programs, potentially reducing AD prevalence and offering broader public health benefits.
reference link : https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13561