A team of scientists has published a study that heightens concerns over the detrimental impact of the apolipoprotein E (APOE4) allele, the most prevalent genetic risk for Alzheimer's disease, upon cognition, olfaction, and metabolic brain indices in healthy urban children and teens. The research report (“Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein E4 Children Exposed to Air Pollution”) appears in the Journal of Alzheimer's Disease.

These children have lifetime exposures to concentrations of air pollutants above current U.S. standards, including fine particulate matter (limit of PM 2.5). Metropolitan Mexico City is an example of extreme urban growth and serious environmental pollution and eight million children are involuntarily exposed to harmful concentrations of PM 2.5 every day since conception.

The study focused on children's and teens' cognitive and olfaction responses using the Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test. Researchers measured three major brain metabolites in hippocampus, pons, and the white matter of the frontal and parietal lobes using proton magnetic resonance spectroscopy. Carriers of the APOE4 versus E3 children had a key metabolite NAA/Cr ratio reduced in the right frontal white matter and showed significant decrements on attention and short-term memory.

A worrisome finding in this study was the below-average scores in Verbal and Full Scale IQ (>10 points) in the Mexico City carriers of the gene associated with the risk for Alzheimer's. APOE4 children had problems with odor detection and failed to identify the smell of soap more often than E3 carriers. Interestingly, this finding strongly correlated with the left hippocampus mI/Cr ratio, a ratio of key importance in Alzheimer's patients.

“APOE4 is likely playing a role in Mexico City children's response to their cumulative air pollution exposures. Of importance for health and educational issues, since Mexico City children mostly attend underprovided public schools that do not help in the development of executive function skills and do not build cognitive reserves, the >10 point IQ difference will likely have a negative impact on academic and social issues, including bullying and teen delinquency,” said investigators Lilian Calderon-Garciduenas, M.D., Ph.D., from the Center for Structural and Functional Neurosciences, University of Montana, and Amedeo D'Angiulli, Ph.D., department of neuroscience, Carleton University.

“The results add to growing data suggesting APOE4 carriers could have a higher risk of developing early AD if they reside in a polluted urban environment,” added Dr. Calderon-Garciduenas.

The authors argue that sustained exposures to urban air pollution result in cognitive underperformance and metabolic brain changes that reflect glial and neuronal alterations. The combined effects of residency in a highly polluted city and APOE4 could lead to an acceleration of neurodegenerative changes.

“APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection, and AD prevention,” wrote the investigators.

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