Association of Physical Activity With Incidence of Dementia Is Attenuated by Air Pollution

David A. Raichlen; Melissa Furlong; Yann C. Klimentidis; M. Katherine Sayre; Kimberly L. Parra; Pradyumna K. Bharadwaj; Rand R. Wilcox; Gene E. Alexander


Med Sci Sports Exerc. 2022;54(7):1131-1138. 

In This Article

Abstract and Introduction


Introduction: Physical activity (PA) is recognized as one of the key lifestyle behaviors that reduces risk of developing dementia late in life. However, PA also leads to increased respiration, and in areas with high levels of air pollution, PA may increase exposure to pollutants linked with higher risk of developing dementia. Here, we investigate whether air pollution attenuates the association between PA and dementia risk.

Methods: This prospective cohort study included 35,562 adults 60 yrs and older from the UK Biobank. Average acceleration magnitude (ACCave) from wrist-worn accelerometers was used to assess PA levels. Air pollution levels (NO, NO2, PM10, PM2.5, PM2.5–10, and PM2.5 absorbance) were estimated with land use regression methods. Incident all-cause dementia was derived from inpatient hospital records and death registry data.

Results: In adjusted models, ACCave was associated with reduced risk of developing dementia (HR = 0.71, 95% confidence interval [CI] = 0.60–0.83), whereas air pollution variables were not associated with dementia risk. There were significant interactions between ACCave and PM2.5 (HRinteraction = 1.33, 95% CI = 1.13–1.57) and PM2.5 absorbance (HRinteraction = 1.24, 95% CI = 1.07–1.45) on incident dementia. At the lowest tertiles of pollution, ACCave was associated with reduced risk of incident dementia (HRPM 2.5 = 0.66, 95% CI = 0.49–0.91; HRPM 2.5 absorbance = 0.60, 95% CI = 0.44–0.81). At the highest tertiles of these pollutants, there was no significant association of ACCave with incident dementia (HRPM 2.5 = 0.88, 95% CI = 0.68–1.14; HRPM 2.5 absorbance = 0.79, 95% CI = 0.60–1.04).

Conclusions: PA is associated with reduced risk of developing all-cause dementia. However, exposure to even moderate levels of air pollution attenuates the benefits of PA on risk of dementia.


Engagement in physical activity (PA) is one of the key lifestyle behaviors often associated with reduced risk of developing dementia or Alzheimer's disease in meta-analyses of prospective cohorts.[1–4] Although the underlying pathways remain unclear, researchers have suggested that PA improves vascular and metabolic health, reduces age-related cognitive and brain structural decline, increases production of neurotransmitters and growth factors related to brain structural health, and alters key biomarkers associated with neurodegenerative disease, including reduced amyloid-β levels in the brain.[5] The weight of available evidence has led the Lancet Commission on dementia prevention and the Committee on Preventing Dementia and Cognitive Impairment from the U.S. National Academies of Sciences, Engineering, and Medicine to include PA as a recommended behavioral modification that may reduce the risk of developing dementia or Alzheimer's disease.[3,6]

Although epidemiological evidence suggests that PA improves brain health and disease prevention, there may be circumstances in which the benefits of PA are inconsistent. For example, exposure to air pollution is increasingly recognized as a potential risk factor for the development of dementia in older adults.[3] Specifically, exposure to particulate matter (PM2.5) and other pollutants (including NO and NO2) has been linked to age-related cognitive decline and increased risk of neurodegenerative disease.[7,8] There is some evidence that inhalation of gases or PM induces inflammatory responses, microglial activation, and the deposition of amyloid plaques in the brain.[9,10] Although PA generally improves cardiovascular and respiratory health through several mechanisms, including beneficial changes in inflammatory status, improved blood flow, and decreases in myocardial oxygen demand,[11] PA may also exacerbate the effects of pollution on health because it effectively increases exposure to pollutants due to higher respiration rates (higher minute ventilation: the volume of air displaced per minute of respiration) compared with rest.[12] For example, during cycling commutes, individuals have minute ventilation two to five times higher than at rest, leading to a larger volume of lung exposure to air pollution, and higher fractions of PM deposited in the respiratory tract or bloodstream.[12] Acute exposure to air pollution during exercise is associated with altered blood biomarkers of inflammation and cardiovascular risk,[13] reduced pulmonary function and airway inflammation,[14] and attenuated exercise-induced increases in circulating brain-derived neurotrophic factor, a protein thought to be at least partially responsible for the brain benefits of exercise.[15]

Previous work has shown that PA in areas of high pollution may diminish the benefits of exercise for overall health. For example, Lin et al.[16] showed that high levels of PA exacerbated the effects of air pollution on stroke risk. In addition, a recent meta-analysis demonstrated that exercise in areas of high air pollution was associated with decreased pulmonary function and increased vascular damage that are both linked with negative health outcomes.[14] Similarly, exposure to black carbon, a constituent of PM2.5, was found to reduce the benefits of PA for lung function.[17] However, many studies find no significant interaction between PA and pollution on risk of myocardial infarction,[11] arterial stiffness,[18] hypertension,[19] diabetes,[20] and cardiovascular or respiratory mortality.[21]

Although the balance of these results suggests that pollution may not affect the health benefits of PA, these studies all used self-reported questionnaires to assess activity levels, which are often prone to recall and social desirability biases.[22] To date, we are not aware of any study that has examined the interaction between PA as measured by accelerometry and air pollution exposure on the risk of developing dementia. The goal of this study is to determine how objectively measured PA and air pollution interact to alter or attenuate the risk of developing all-cause dementia in a large prospective study, the UK Biobank. We predict that PA will be associated with reduced risk of incident dementia in low and moderate levels, but not in the highest levels of pollution exposure.