Underpinnings of Air Pollution and Dementia Risk Explained?

Batya Swift Yasgur, MA, LSW

July 26, 2023

A new study sheds light on the biological underpinnings that may explain the association between air pollution and the development of dementia.

Investigators found that high levels of homocysteine and low levels of methionine are associated with increased risk of dementia in the presence of air pollution. Homocysteine is an amino acid associated with increased risk of cardiovascular disease (CVD) and dementia; methionine is an amino acid that's a precursor of homocysteine,

Study investigator Giulia Grande, MD, PhD, a postdoctoral researcher at the Aging Research Center, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News that her team was able to establish the harmful effects of pollution on human health in Stockholm — a city with low levels of pollution — and that these effects were mediated by the levels of these amino acids.

"We can only expect worse outcomes in other, more polluted cities, which calls for the need to intensify the control of emissions, as they are known to have numerous negative health effects," she said.

The study was published online July 19 in the journal Neurology.

A Known Dementia Risk Factor

"Air pollution is now acknowledged as a possible risk factor for dementia; however, we have a poor understanding of the biological underpinnings of the association between air pollution and dementia," Grande said.

Findings from animal and human studies suggest polluted air can cause higher brain amyloid-beta deposition and neurodegeneration. Previous research has demonstrated that methionine is involved in normal brain function, and low levels have been linked with dementia and brain aging. In turn, high levels of homocysteine have been associated with vascular and cellular damage, with subsequent insult to brain structures, she explained.

The mechanisms at play in the association between high homocysteine levels and low methionine levels with dementia are "complex and only partly understood," Grande noted.

There has been little research on the impact of air pollution on these amino acids, but one recent study showed positive association between high levels of particulate matter and homocysteine, and low levels of methionine.

"We wanted to further investigate the possible mechanisms and test whether altered blood concentrations of these two vitamin B-related amino acids could at least partly explain this link," Grande said.

The researchers also examined whether cardiovascular diseases (CVDs) played a role in this association, or whether homocysteine and methionine have an independent mediating effect.

For the study, investigators used data from the ongoing SNAC-K study, a population-based longitudinal study of adults age 60 years and older living in central Stockholm's Kungsholmen district.

After a baseline evaluation, 2512 dementia-free participants aged 60-78 years were followed every 6 years, while those 78 and older were followed every 3 years. At baseline, participants underwent blood testing, and provided socioeconomic data and information about physical activity and diet.

At each visit, clinical and laboratory testing was conducted, and patients were interviewed to determine cognitive status.

The total effect of air pollution on dementia risk was categorized into 4 pathways: direct effect; indirect effect (mediation); effect due to interaction; and effect due to both mediation and interaction.

High Homocysteine

Investigators calculated the annual average levels of particulate matter (PM2.5) at participants' home addresses and found a 70% increased hazard of dementia per unit of increased PM2.5 exposure during the 5 years before baseline. PM2.5 consists of pollutant particles of less than 2.5 microns in diameter suspended in air.

Results showed a higher dementia risk per unit (µg/m3) increase of PM2.5 during the 5 years prior to baseline (hazard ratio [HR], 1.71; 95% CI, 1.33 - 2.09) after adjusting for other factors.

In addition, 51.6% (95% CI, 9% - 94.1%) of the total effect of PM2.5 on dementia was due to mediation and/or interaction with homocysteine, with 6.6% (95% CI, 1.6% - 11.6%) attributable to mediation only and 47.8% (95% CI, 4.9% - 91.7%) attributable to interaction. Close to half (48.4%) of the association could be attributed to a direct effect (P = .03).

Roughly half of the increased PM2.5-related dementia risk was attributable to an interaction between the air pollution and high levels of homocysteine or low levels of methionine.

On the other hand, high levels of methionine reduced the dementia hazard associated with PM2.5 exposure by 31% (HR, 0.69; 95% CI, 0.56 - 0.85), of which 24.8% was attributable to the interaction with methionine and 25.9% was attributable to the direct effect of PM2.5 (P = .001).

"No mediation affect was found through methionine," the authors report, adding that findings for homocysteine were "attenuated" after excluding participants who developed CVDs, but remained similar for methionine.

"High levels of homocysteine enhanced the dementia risk attributed to air pollution, while high methionine concentrations reduced the risk," the researchers note.

"The impact of homocysteine on cardiovascular conditions partly explains this association, [but] alternative pathways other than cardiovascular mechanisms may be at play between methionine and dementia," they suggest.

Multiple Mechanisms

Commenting for Medscape Medical News, Andrew Sommerlad, PhD, associate professor, division of psychiatry, University College London, UK, said the findings of this "further strengthen the evidence that air pollution is detrimental to brain health."

Sommerlad, who was not involved with the study, called the exact ways by which pollution increases risk of dementia unknown. But the study "suggests that there may be multiple mechanisms."

The fact that the increased risk is seen even in a country like Sweden, with relatively low levels of pollution, "highlights the pressing need for all countries, particularly those with much higher air pollutions levels, to adhere to the World Health Organization's strict air quality recommendations," said Sommerlad, who is also a Consultant Old Age Psychiatrist with Islington Memory Service in London.

The study was funded by Swedish Ministry of Health and Social Affairs, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare and several Swedish foundations. Grande, co-authors, and Sommerlad report no relevant financial relationships.

Neurology. Published online July 19, 2023. Abstract

Batya Swift Yasgur, MA, LSW is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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