Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype

J Alzheimers Dis. 2023;93(1):193-209. doi: 10.3233/JAD-221054.


Background: Fine particulate matter (PM2.5) and nitrogen dioxide (NO2) measures of ambient air pollution are associated with accelerated age-related cognitive impairment, and Alzheimer's disease and related dementias (ADRD).

Objective: We examined associations between air pollution, four cognitive factors, and the moderating role of apolipoprotein E (APOE) genotype in the understudied period of midlife.

Methods: Participants were ∼1,100 men in the Vietnam Era Twin Study of Aging. Baseline cognitive assessments were from 2003 to 2007. Measures included past (1993-1999) and recent (3 years prior to baseline assessment) PM2.5 and NO2 exposure, in-person assessment of episodic memory, executive function, verbal fluency, and processing speed, and APOE genotype. Average baseline age was 56 years with a 12-year follow-up. Analyses adjusted for health and lifestyle covariates.

Results: Performance in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains: PM2.5 with executive function and NO2 with episodic memory. Higher PM2.5 exposure was related to worse executive function in APOE ɛ4 carriers, but not in non-carriers. There were no associations with processing speed.

Conclusion: These results indicate negative effects of ambient air pollution exposure on fluency alongside intriguing differential modifications of cognitive performance by APOE genotype. APOE ɛ4 carriers appeared more sensitive to environmental differences. The process by which air pollution and its interaction with genetic risk for ADRD affects risk for later life cognitive decline or progression to dementia may begin in midlife.

Keywords: PM2.5; APOE genotype; Aging; air pollution; cognition; midlife; nitrogen dioxide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Air Pollutants*
  • Air Pollution* / adverse effects
  • Air Pollution* / analysis
  • Apolipoproteins E / genetics
  • Cognition
  • Environmental Exposure / adverse effects
  • Genotype
  • Humans
  • Male
  • Nitrogen Dioxide
  • Particulate Matter / adverse effects
  • Particulate Matter / analysis


  • Nitrogen Dioxide
  • Particulate Matter
  • Apolipoproteins E
  • Air Pollutants