White Matter Hyperintensities, Systemic Inflammation, Brain Growth, and Cognitive Functions in Children Exposed to Air Pollution

Article type: Research Article

Authors: Calderón-Garcidueñas, Lilian^{a; b; *} | Mora-Tiscareño, Antonieta^a | Styner, Martin^c | Gómez-garza, Gilberto^a | Zhu, Hongtu^d | Torres-Jardón, Ricardo^e | Carlos, Esperanza^a | Solorio-López, Edelmira^a | Medina-Cortina, Humberto^a | Kavanaugh, Michael^b | D'Angiulli, Amedeo^f

Affiliations: [a] Instituto Nacional de Pediatría, Mexico City, Mexico | [b] The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT, USA | [c] Department of Psychiatry and Computer Science, University of North Carolina, Chapel Hill, NC, USA | [d] Biostatistics, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA | [e] Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico | [f] Department of Neuroscience, Carleton University, Ottawa, ON, Canada

Correspondence: [*] Correspondence to: Lilian Calderón-Garcidueñas MD, PhD, The Center for Structural and Functional Neurosciences, The University of Montana, 32 Campus Drive, Skaggs Building 287, Missoula, MT 59812, USA. Tel.: +1 406 243 4785; E-mail: lilian.calderon-garciduenas@umontana.edu.

Abstract: Air pollution exposures are linked to neuroinflammation and neuropathology in young urbanites. Forty percent of exposed children and young adults exhibit frontal tau hyperphosphorylation and 51% have amyloid-β diffuse plaques compared to 0% in low pollution controls. In older adults, white matter hyperintensities (WMH) are associated with cognitive deficits while inflammatory markers correlate with greater atrophy than expected for age. We investigated patterns of WMH, magnetic resonance imaging (MRI) volume growth, blood inflammatory mediators, and cognition in matched children from two urban cohorts: one severely and one minimally exposed to air pollution. Baseline and one year follow-up measurements of cognitive abilities, brain MRI volumes, and blood were collected in 20 Mexico City (MC) children (10 with WMH+, and 10 without WMH−) and 10 matched controls (WMH−). MC WMH− children display the profile of classical pro-inflammatory defensive responses: high interleukin 12, production of powerful pro-inflammatory cytokines, and low concentrations of key cytokines and chemokines associated with neuroprotection. MC WMH+ children exhibit a response involved in resolution of inflammation, immunoregulation, and tissue remodeling. The MC WMH+ group responded to the air pollution-associated brain volumetric alterations with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to MC WMH−. We conclude that complex modulation of cytokines and chemokines influences children's central nervous system structural and volumetric responses and cognitive correlates resulting from environmental pollution exposures. Identification of biomarkers associating systemic inflammation to brain growth is critical for detecting children at higher risk for cognitive deficits and neurodegeneration, thereby warranting early implementation of neuroprotective measures.

Keywords: Air pollution, Alzheimer's disease risk, biomarkers, chemokines, children, cognition, cytokines, fine particulate matter, MRI volumes, systemic inflammation, white matter hyperintensities

DOI: 10.3233/JAD-2012-120610

Journal: Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 183-191, 2012