Exposure to particulate matter smaller than 2.5 microns in diameter (PM_2.5) was associated with increased risk of dementia, a meta-analysis suggested.

Across 14 studies that assessed PM_2.5, the overall risk of dementia rose by 4% (HR 1.04, 95% CI 0.99-1.09) for every 2 μg/m³ increase in average annual PM_2.5 concentration, according to Marc Weisskopf, PhD, ScD, of Harvard T.H. Chan School of Public Health in Boston, and colleagues.

But among seven studies that used active case ascertainment — a method that involves in-person evaluations of people who did not have dementia at baseline — dementia risk rose by 42% (HR 1.42, 95% CI 1.00-2.02), Weisskopf and co-authors reported in The BMJ. A more conservative estimate, after removing four studies due to possible concerns about time trend bias and causally relevant time windows, was HR 1.17 (95% 0.96-1.43), the researchers said.

Among seven studies that used passive surveillance methods like electronic health records, the HR was 1.03 (95% 0.98-1.07).

“This is a big step in providing actionable data for regulatory agencies and clinicians in terms of making sense of the state of the literature on this hugely important health topic,” Weisskopf said in a statement.

“The results can be used by organizations like the Environmental Protection Agency [EPA], which is currently considering strengthening limits on PM_2.5 exposure,” Weisskopf added. “Our findings support the public health importance of such a measure.”

The study is the first such systematic review and meta-analysis to use active case ascertainment. It’s also the first to use the new Risk of Bias in Non-Randomized Studies of Exposure (ROBINS-E) tool, which provides a structured approach to assessing bias in observational epidemiological studies.

“Evidence that a reduction in air pollution is associated with a lower incidence of dementia is only just emerging,” noted Andrew Sommerlad, PhD, and Kathy Liu, MRCPsych, both of University College London, in an accompanying editorial.

This new systematic review highlights many remaining uncertainties about links between air pollution and dementia, the editorialists observed. “Risk factors for dementia cluster together, many of which are driven by socioeconomic status, and the interactions between risk factors are likely to be complex,” they pointed out.

“Many studies have attempted to resolve this issue by adjusting for potential confounders, but this adjustment might not be adequate because the manipulation could obscure the complex inter-relations between socioeconomic status, ethnic group, air pollution, and dementia,” Sommerlad and Liu wrote.

While air pollution is considered a modifiable risk factor for dementia globally, PM_2.5 concentrations in major cities vary widely from 10µg/m³ in Toronto, Canada, to more than 100µg/m³ in Delhi, India, they added.

In January, the EPA sought to tighten the national annual limit on particulate matter pollution by proposing updates to the National Ambient Air Quality Standards for Fine Particulate Matter, aiming to lower the primary (health-based) annual PM_2.5 standard to 9.0-10.0 µg/m³, down from its current cutoff of 12.0 µg/m³.

In their review, Weisskopf and co-authors identified 51 studies that evaluated an association between ambient air pollution and clinical dementia. Most studies were from North America or Europe; some were from Asia or Australia. All publications were from the past 10 years.

The researchers assessed the studies for bias using ROBINS-E and included 16 studies in their meta-analyses. Most evaluated PM_2.5. Some looked at nitrogen dioxide, nitrogen oxide, or ozone.

In nine studies, the overall HR per 10 μg/m³ of nitrogen dioxide was 1.02 (95% CI 0.98-1.06). In five studies, the HR per 10 μg/m³ of nitrogen oxide was 1.05 (95% CI 0.98-1.13). Ozone showed no clear association with dementia.

The PM_2.5 findings indicate links between ambient air pollution and clinical dementia may be consistent, even below the EPA annual standard of 12 μg/m³ or the U.K. (20 μg/m³) and the European Union (25 μg/m³) limits, the researchers suggested.

“Given the massive numbers of dementia cases, identifying actionable modifiable risk factors to reduce the burden of disease would have tremendous personal and societal impact,” Weisskopf said. “Exposure to PM_2.5 and other air pollutants is modifiable to some extent by personal behaviors — but more importantly, through regulation.”

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