A Tale of Two Cohorts: One City, Similar Air Quality

Air pollution was associated with lower baseline cognitive scores and more rapid cognitive decline in one northern Manhattan cohort but not another, a prospective study found.

For each interquartile range (IQR) increase in residential nitrogen dioxide (NO₂), adjusted models showed that participants in the Washington Heights–Inwood Community Aging Project (WHICAP) had a 0.22 standard deviation (SD) lower global cognitive score on enrollment and 0.06 SD more rapid decline in cognitive score between biennial visits. Results were similar for two other pollutants, fine particulate matter (PM_2.5) and respirable particulate matter (PM₁₀).

However, those in the Northern Manhattan Study (NOMAS) cohort showed no consistent association between air pollution and cognitive function, reported Erin Kulick, PhD, of Brown University in Providence, Rhode Island, and coauthors in Neurology.

NOMAS participants were slightly younger, had lower prevalence of cardiovascular disease, and were more likely to be Hispanic. Although average air pollution levels were similar, variability was decreased for NOMAS versus WHICAP participants.

“While the magnitude of the observed associations in this study may appear small, if these associations represent a causal effect, the implications for global public health would be pronounced,” Kulick and colleagues wrote. “Specifically, the association between NO₂ and the accelerated rate of cognition decline was comparable to approximately 1 year of aging.”

Age, cerebrovascular disease, and cardiovascular risk factors do not fully account for cognitive decline and “identification of novel risk factors, particularly modifiable risk factors, is of great importance,” they added.

Air pollution has emerged as a risk factor for cognitive decline in addition to its association with other cardiovascular and neurologic outcomes.

Proposed mechanisms include a systemic circulatory response and direct toxicity following translocation to the brain through the lungs or olfactory bulb. Effects include vascular inflammation, impaired microvascular reactivity, and changes in cerebral hemodynamics. Autopsied brains of dogs and children in high versus lower pollution areas of Mexico City showed an association with cerebral microvascular damage and inflammation.

Research on the association between air pollution and cognitive decline has shown mixed results. While the National Social Health and Aging Project found decreased cognitive function associated with long-term PM_2.5 and NO₂ exposure in an older American cohort, a recent British cohort showed no association in adjusted analysis. The EPA concluded in its 2019 integrated science assessment (ISA) on particulates that “since the 2009 PM ISA, the literature base has greatly expanded, and the combination of animal toxicological and epidemiologic evidence supports a likely to be causal relationship between long-term PM_2.5 exposure and nervous system effects.”

The present study examined the association between long-term exposure to ambient residential air pollution and cognitive decline among older adults in northern Manhattan. Data from WHICAP comprised 5,330 participants and from NOMAS 1,093. Participants in both had no dementia at baseline, at least one neuropsychological examination during the study period, and a primary address in New York City.

WHICAP is a prospective, population-based study of aging and dementia begun in 1992, enrolling Medicare-eligible adults 65 or older with second and third recruitment waves in 1999 and 2010. Patients are evaluated once every 18 to 24 months. Average age was 74 and 33% were men. White non-Hispanic people made up 15% of the sample, black non-Hispanic people 31%, and Hispanic people 43%.

NOMAS is a prospective, population-based cohort study of participants designed to measure cardiovascular risk factors and outcomes. Permanent Manhattan residents were enrolled from 1993 to 2001; between 2003 and 2008, a subgroup of participants 50 or older with no history of stroke underwent MRI and neuropsychological testing. Average age of people was 70 and 39% were men. White non-Hispanic persons were 14% of the cohort, black non-Hispanic persons 17%, and Hispanic persons 66%.

Using NO₂, PM_2.5, and PM₁₀ data from the EPA Air Quality System, researchers derived annual average values to predict concentrations by address. Distances to roadways were 301 meters in WHICAP and 321 meters in NOMAS. Mean estimated exposures [and IQR] for WHICAP and NOMAS cohorts, respectively, were:

• NO₂ (parts per billion, or ppb): 31.88 [12.32] versus 30.51 [13.16]
• PM_2.5 (μg/m³): 13.07 [4.81] versus 13.88 [1.34]
• PM₁₀ (μg/m³): 20.93 [9.90] versus 16.21 [5.37]

In WHICAP, one IQR increase in PM_2.5 and PM₁₀ was predictive of lower baseline global cognitive scores and more rapid rates of decline in global cognitive scores between visits. Cognitive function was calculated based on standardized baseline z scores with cohort-specific means and SDs. Researchers developed a global score and scores for memory, executive function, and language.

In an accompanying editorial, Jennifer Weuve, MPH, ScD, of Boston University noted that ambient NO₂ concentrations near most WHICAP participant homes fell below the U.S. regulatory annual standard of 53 ppb.

“These measured exposure levels could be surrogates for etiologically pertinent and higher levels from an earlier period,” she wrote. “Yet adverse associations observed at subregulatory standard levels raises questions about whether those standards are sufficiently low to protect population health.”

Studying individuals with no dementia, stroke, or cardiac events from a preexisting cohort likely contributed to significant selection bias in this study, Kulick and colleagues noted. Other limitations included lack of data about some participants because cognitive impairment prevented follow-up. In addition, older patient age at enrollment provided a limited opportunity to include data about possibly-more-important midlife risk factors for cognitive decline.

1. Greater air pollution was associated with lower baseline cognitive scores and more rapid cognitive decline in one northern Manhattan cohort but not another, a prospective study showed.

2. In the Washington Heights–Inwood Community Aging Project (WHICAP) cohort, one IQR increase in fine particulate matter and respirable particulate matter predicted lower baseline cognitive scores and more rapid rates of decline.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Environmental Health, the National Institute of Aging, and the Environmental Protection Agency.

The researchers reported no disclosures. The editorialist serves on the Health Effects Institute’s advisory panel of Traffic-Related Health Effects and is a consultant for the Alzheimer’s Association.

Cat ID: 494

Topic ID: 398,494,282,494,730,361,192,149,150,60,925