Unraveling the Complex Relationship between Air Pollution, Genetics, and Dementia

APOE genotype modifies the link between ambient air pollution and cognitive function.

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A new study led by scientists at the University of California San Diego has found that exposure to ambient air pollution may increase the risk of developing dementia, with the risk further complicated by genetics. 

The research builds on a 2018 study commissioned by The Lancet, which listed 12 modifiable risk factors that increase the risk of dementia, including three new ones: excessive alcohol, head injury, and air pollution.

The researchers examined cognitive assessments of approximately 1,100 men in their 40s and 50s with an average baseline age of 56, participating in the ongoing Vietnam Era Twin Study of Aging. 

The new study had a follow-up period of 12 years. In addition to cognitive assessments, the researchers measured participants’ exposure to particular matter (PM2.5) and nitrogen dioxide (NO2) in the air and assessed their APOE genotypes.

APOE is a gene that provides instructions for making a protein crucial to transport cholesterol and other fats in the bloodstream. The APOE-4 allele of this gene has been identified as a strong risk factor for Alzheimer’s disease.

First author Carol E. Franz, Ph.D., professor of psychiatry and co-director of the Center for Behavior Genetics of Aging, said, “The 2020 Lancet report concluded that modifying 12 risk factors, which include others like education and depression at midlife, could reduce dementia incidence by as much as 40%.” 

The researchers found that participants with higher exposure to PM2.5 and NO2 in their 40s and 50s displayed worse cognitive functioning in verbal fluency from age 56 to 68. Additionally, persons with the APOE-4 allele appeared even more sensitive, with those exposed to higher PM2.5 levels showing worse outcomes for executive function and those with higher NO2 exposure showing worse outcomes involving episodic memory.

The study underscores the importance of identifying modifiable risk factors, such as air pollution, early in life to reduce the incidence of dementia. It also suggests that the processes by which air pollution affects the risk for later-life cognitive decline begin earlier than previously thought.

The 2020 Lancet report concluded that modifying 12 risk factors, which include others like education and depression at midlife, could reduce dementia incidence by as much as 40%. However, this new study places ambient air pollution as a greater risk for Alzheimer’s and related dementias than diabetes, physical activity, hypertension, alcohol consumption, and obesity.

A new study found that exposure to ambient air pollution, such as car exhaust and power plant emissions, is associated with a measurably greater risk of developing dementia over time. The researchers also found that those with the APOE-4 allele, a gene that is a strong risk factor for Alzheimer’s disease, are even more sensitive to the effects of air pollution. 

The study suggests that exposure to ambient air pollution may increase the risk of developing dementia, and those with the APOE-4 gene are more sensitive to its effects. These findings highlight the importance of identifying modifiable risk factors early in life and the need to address air pollution as a potential risk factor for Alzheimer’s disease and related dementias.

Journal Reference:

  1. Franz, Carol E. et al. ‘Associations between ambient air pollution and cognitive abilities from midlife to early old age: Modification by APOE Genotype.’ DOI: 10.3233/JAD-221054
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