Uncovering environmental exposures linked with Alzheimer’s and related dementias
Amid the increasing prevalence of Alzheimer’s disease and related dementias (ADRD), a team led by researchers from Harvard T.H. Chan School of Public Health and Harvard Medical School has conducted what they describe as the most extensive systematic evaluation to date of associations between ADRD and nearly 200 environmental exposures—from pollution to diet to social connections. The researchers also produced a first-of-its-kind exposomic risk score that can help predict people’s risk of these diseases and could therefore contribute to prevention strategies.
The study was published Sept. 29 in the journal Alzheimer’s & Dementia. Chenshuang Li, a postdoctoral fellow at Harvard Chan School, was first author. Peng Gao, assistant professor of environmental health and exposomics at Harvard Chan, was a co-corresponding author along with Harvard Medical School’s Chirag Patel. Gao studies the exposome—all the environmental exposures people face across their lifespan—and how these exposures impact health.
Although genetic factors are involved in ADRD, most cases cannot be attributed to genetics alone, and previous research has suggested that environmental exposures also play a significant role. Using data from the UK Biobank—a database that collects health, genetic, and lifestyle data over time—the study followed nearly 500,000 participants for a median of 15.3 years. Researchers conducted an exposome-wide association study examining 193 exposures across five domains: chemical, such as air pollutants and medications; physical, such as noise; lifestyle, such as diet, physical activity, and sleep; social, such as education and socioeconomic status; and ecosystems, such as access to green space.
The study identified 76 exposures significantly linked with ADRD and 34 linked with Alzheimer’s disease specifically. In the social domain, significant risk factors included unemployment, financial difficulties, lower educational attainment, and poor housing conditions, such as renting rather than owning a home. Lifestyle risk factors included never eating eggs, current smoking, improper alcohol consumption, frequent daytime dozing, and sleeping more or less than the optimal amount. Other factors linked with higher ADRD risk included chemical exposures, particularly nitrogen dioxide air pollution, and multiple medication use, which the authors said likely reflects underlying health complexity rather than direct effects of the drugs.
Additionally, the study found potential protective factors against ADRD, including physical activities such as walking for pleasure, other exercise, and heavy do-it-yourself activities like yard work; eating cheese and poultry; computer and mobile phone use; living with a partner; and higher household income. The authors cautioned that these are associations from an observational study and that further research is needed to rule out reverse causation and confounding.
The researchers also developed a novel exposome-based ADRD risk prediction model and an exposomic risk score to help stratify distinct risk groups in a population. Adding environmental exposures to a model based on demographics and APOE genotype—the best-known genetic risk factor for Alzheimer’s—improved its ability to predict who would develop ADRD. People with risk scores in the highest quarter were nearly three times as likely to develop ADRD during follow-up as those in the lowest quarter. The authors noted that the score still needs to be validated in other, more diverse populations.
The co-authors noted that their findings could support the development of multi-component intervention strategies targeting modifiable exposures for ADRD prevention—an effort, they wrote, “which may prove essential for reducing the growing burden of dementia.”
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Learn more:
How pollutants interact inside the body to impact health (Harvard Chan School news)
