Infection Plus Pollution Equals Increased Alzheimer’s Risk

The combination of a history of infection and exposure to air pollution from traffic increased the risk of Alzheimer’s disease (AD) by 177% in adults ages 60-75, according to data from nearly 100,000 people.

Svetlana V. Ukraintseva, PhD, a research professor of biodemography of aging at Duke University in North Durham, said a growing evidence base suggests that susceptibility to infections plays a role in the development of Alzheimer’s, but the mechanism of action remains unclear. Carolina and colleagues in a poster presented at the annual meeting of the Gerontological Society of America.

“My view on Alzheimer’s disease is that Alzheimer’s is a ‘multi-hit’ disease that requires not one but several risk factors to ‘hit’ a person into the clinical stage,” Ukraintseva said in an interview. said Ukraintseva.

AD risk factors/hits include high exposure to traffic-related air pollution (TRAP) and infections, as well as the following factors: hypertension, depressionsleep disorders, brain trauma, as well as genes and their components APOE4 and single nucleotide polymorphism rs6859 said.

In a previous study, researchers found a significant synergistic effect of TRAP and APOE4 On hippocampal volume, one of the biomarkers of neurodegeneration, Ukraintseva said: Medscape Medical News. “As a next step, we decided to evaluate the joint effect of high exposure to TRAP and infections (another AD risk factor) on AD,” he said.

In the current study, researchers examined risk factors that may synergistically increase the risk of AD and predict the clinical onset of AD with more than 80% probability, Ukraintseva said. He explained that identifying combinations of risk factors is important for the prevention of AD because targeting multiple risk factors simultaneously in the same individual at the preclinical stage can potentially prevent the clinical onset of AD in many cases.

The researchers used data from the UK Biobank for 51,079 women and 48,983 men aged 60 to 75, where data on infectious diseases, Alzheimer’s and other dementias were available. High exposure to TRAP was defined as the primary residence being 50 meters or less from a major road.

Overall, the presence of both a history of infection and exposure to TRAP was associated with a 164% higher risk of onset of AD after age 75 years (hazard ratio, 2.64) compared with individuals with neither a history of infection nor exposure to TRAP. .

Potential mechanisms driving this association include disruption of the integrity of the blood-brain barrier as a result of TRAP, which may make the brain more vulnerable to infections and related damage, the researchers wrote in their poster.

Ukraintseva said the current findings were not unexpected, given previous data on the concept of multiple-hit AD risk. Medscape Medical News.

“Targeting several AD risk factors simultaneously in the same individual can potentially prevent the clinical onset of most cases of AD, especially if these factors synergistically increase the risk of AD,” Ukraintseva said. Stating that he and his team plan to investigate the effect of other risk factor combinations on the clinical onset of AD, he said, “More research is needed in this direction, and this is currently not sufficiently researched.”

Focus on Prevention Strategies and Stronger Studies

Given limited treatment options and a lack of cures, preventing AD remains an important strategy, Ryan T. Demmer, MPH, professor of epidemiology at the Mayo Clinic in Rochester, Minnesota, said in an interview.

“There is strong evidence that serious infections play a role in the etiology of AD,” Demmer said. “The assumption that air pollution has adverse effects on multiple organ systems is also strong, and there is significant evidence linking TRAP to cardiovascular disease and diabetes, both of which are linked to increased risk of dementia,” he said.

Demmer was “somewhat surprised” by the strength of the relationships in the current study, given the high degree of measurement error in measuring air pollution and infection; This often reduces the findings to a weaker or no relationship.

Limitations of the current study include using ICD codes alone to identify infections, which could contribute to measurement error, Demmer said. If doctors suspect infection, patients may be classified as such even if further examination shows no infection, he noted. “There is also the potential for measurement error to manifest differently between individuals at high and low risk for developing AD,” Demmer said. “Older individuals with more risk factors for AD may be more likely to seek medical care for mild infections and document the ICD code in their medical records, while younger, healthier individuals may be less likely to seek care,” he said.

Additionally, “Air pollution information is address-based, but people spend different amounts of time at their home address, which creates a lot of bias in their communities about how much exposure they have to air pollution,” Demmer said. “Confounding in this study is also a concern; “Common causes of infections and Alzheimer’s, such as health behaviors or comorbidities, may explain this association, and these factors do not appear to be taken into account,” he said.

Additional research is needed to determine the causality of the relationships between air pollution, infections and Alzheimer’s, Demmer said. Medscape Medical News. “A few examples include studies that can more robustly quantify potential confounders, more carefully quantify infectious disease and air pollution history, and/or directly investigate underlying biological mechanisms,” he said.

Demmer added that although the lack of causality limits the impact of the study findings on clinical practice at this time, “there is little downside to recommending that patients take precautions to prevent serious infections and minimize exposure to air pollution.”

The study was supported by the National Institute on Aging of the National Institutes of Health. The researchers had no financial conflicts to disclose. Demmer had no financial conflicts to disclose.