Vascular Conditions Offer No Clarity on Pollution-Dementia Link

Investigators appeared to rule out vascular dysfunction mediating the previously reported link between fine particulate matter (PM_2.5) and dementia.

Contrasting with prior studies, their nationally representative U.S. cohort study found no significant association between greater long-term exposure to PM_2.5 and a higher dementia risk 10 years later (HR 1.04, 95% CI 0.98-1.11).

Sensitivity analysis suggested a link between chronic PM_2.5 exposure and incident dementia among those with hypertension at baseline. However, there was no statistically significant association seen between PM_2.5 and stroke or hypertension:

• Stroke: OR 1.08 per quartile of PM_2.5 (95% CI 0.91-1.29)
• Hypertension: OR 0.99 per quartile of PM_2.5 (95% CI 0.92-1.07)

“These findings suggest that although hypertension may enhance the susceptibility of individuals to air pollution, hypertension and stroke do not significantly mediate or modify the association of PM_2.5 with dementia, indicating the need to investigate other pathways and potential mediators of risk,” concluded Boya Zhang, PhD, of the University of Michigan School of Public Health in Ann Arbor, and collaborators of the Environmental Predictors of Cognitive Health and Aging (EPOCH) Project in JAMA Network Open.

Previously, a rise in dementia risk has been associated with wildfire smoke and overall worsening air quality, with PM_2.5 proposed as a key factor.

“This does not mean that the previous or this study are wrong, though,” commented Sayantani Sindher, MD, of Stanford Medicine Healthcare in Palo Alto, California, who was not involved in the research. “What this does tell us is that in the cohort for the EPOCH Project that is the focus of this study, PM_2.5 levels were not a significant driver of dementia.”

According to the researchers, PM_2.5 has been associated with vascular conditions such as cardiovascular disease, which suggests a relationship between PM_2.5 and vascular conditions could explain an effect on dementia.

“Via these pathways, as well as the shared mechanisms of inflammation and oxidative stress in the pathways from PM_2.5 and vascular conditions to accelerate cognitive decline, it is possible that pollution exacerbates the impact of vascular disease on cognitive decline even if the vascular disease was not the result of air pollution exposure,” Zhang’s group wrote.

Based on the present study, however, the researchers pointed to the entry of neurotoxic compounds entering the brain, or particles causing inflammation and oxidative stress, as alternate mechanisms mediating the relationship between dementia and exposure to pollution. “Additionally, although the evidence is not conclusive, recent studies suggest that there are mediated pathways through mental health disorders (e.g., depression), poor sleep quality, and insulin resistance or disruption of the normal action of insulin in the brain.”

Among the participants in the study (survey respondents age 50 and older; mean 61 years), 14.7% developed dementia after an average follow-up of 10.2 years. The average PM_2.5 exposure — estimated from residential histories over the course of 10 years — was 12.96 μg/m³ overall, or 12.8 μg/m³ in the dementia-free and 13.8 μg/m³ in those with incident dementia over follow-up.

“Notably there do not appear to be large differences in PM_2.5 exposure in this cohort, so these findings could suggest that for the average individual, PM_2.5 levels are not a common concern for the development of dementia,” Sindher told MedPage Today via email.

“However, this does not completely rule out this potential. Larger differences in PM_2.5 levels over a long period of time that would result in a much higher 10-year PM_2.5 exposure, could still increase the risk of dementia,” she said. “In short, this study shows that the average individual is not exposed to high enough PM_2.5 levels to have an impact on development of dementia, but there is still the possibility of an association of PM_2.5 levels and dementia at higher exposure levels.”

The study included 27,857 Health and Retirement Study participants surveyed from 1998 to 2016. Of this group, 56.5% were women. The population was 69.1% non-Hispanic white, 16.7% non-Hispanic Black, and 11.4% Hispanic. Just over half lived in an urban area, 22.3% in an ex-urban area, and 21.6% in a rural area.

At baseline, 4.8% of participants had had a stroke, and 46.8% had hypertension. During follow-up, these figures grew another 8.2% and 13.8%, respectively.

Patients with incident dementia were more likely to have hypertension and a history of stroke at baseline.

Limitations to the study include its reliance on 10-year average exposure estimates for PM_2.5 based on residential histories, which could have introduced measurement error, Zhang and colleagues acknowledged. The study authors also said they lacked information regarding short-term blood pressure extremes and potentially had hypertension misclassified due to self-reporting by the participants.

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