Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City

Abstract

Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2.5) influence cognition. The Wechsler Intelligence Scale for Children (WISC-R) was administered to 105 Mexico City children (12.32±5.4 years, 69 APOE 3/3 and 36 APOE 3/4). APOE 4v 3 children showed decrements on attention and short-term memory subscales, and below-average scores in Verbal, Performance and Full Scale IQ. APOE 4 females had higher BMI and females with normal BMI between 75-94% percentiles had the highest deficits in Total IQ, Performance IQ, Digit Span, Picture Arrangement, Block Design and Object Assembly. Fasting glucose was significantly higher in APOE 4 children p=0.006, while Gender was the main variable accounting for the difference in insulin, HOMA-IR and leptin (p<.05). Gender, BMI and APOE influence children's cognitive responses to air pollution and glucose is likely a key player. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5-2SD from average IQ). Young female results highlight the urgent need for gender-targeted health programmes to improve cognitive responses. Multidisciplinary intervention strategies could provide paths for prevention or amelioration of female air pollution targeted cognitive deficits and possible long-term AD progression.

Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

“…Although olfactory impairment, or anosmia, occurs during normal aging 95,96 , anosmia frequently precedes many neurological disorders [97][98][99][100][101] . Furthermore, studies have shown correlations with the levels of air pollution with olfactory impairment 34,102-105 and neurodegenerative disease pathology, such as Alzheimer's disease [106][107][108][109][110][111] , though the mechanism behind these correlations is unclear. Anosmia has many causes, such as smoking and head trauma 102 , and toxin exposure is another source of olfactory deficits.…”

Gender Difference in the Effects of Outdoor Air Pollution on Cognitive Function Among Elderly in Korea

“…Although a few studies explored effect modification by gender/sex as a supplementary purpose concerning examining the main effects of air pollution on cognitive function (11,20), the results were varied. Specifically, previous research found that the effect of air pollution exposure on cognition was different between males and females (21,22), while no such result was found for other research (23). Notably, there is a discrepancy over whether the effect is higher in males than females or vice versa (21)(22)(23).…”

Clinical effects of air pollution on the central nervous system; a review

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