Mitochondrial DNA copy number and neurocognitive outcomes in children

Abstract

Low mitochondria DNA copy number (mtDNAcn) has been linked to cognitive decline. However, the role of mtDNAcn in healthy cognitive development is unclear. We hypothesized early-life mtDNAcn would be associated with children’s learning and memory. We quantified mtDNAcn in umbilical cord blood and child blood at ages 5–7 from participants in a prospective birth cohort. We administered the Children’s Memory Scale (CMS) at ages 9–14 (N = 342) and the Wechsler Intelligence Scale for Children (WISC-IV) at ages 7 and 9 (N = 457). Associations between mtDNAcn tertiles and CMS and WISC were evaluated with linear regression and linear mixed-effects models, respectively. We examined non-linear associations using generalized additive mixed models. Relative to the middle tertile of mtDNAcn, lower childhood mtDNAcn was associated with lower WISC Working Memory (β = −2.65, 95% CI [−5.24, –0.06]) and Full-Scale IQ (β = −3.71 [−6.42, −1.00]), and higher CMS Visual Memory (β = 4.70 [0.47, 8.93]). Higher childhood mtDNAcn was linked to higher CMS Verbal Memory (β = 7.75 [2.50, 13.01]). In non-linear models, higher childhood mtDNAcn was associated with lower WISC Verbal Comprehension. Our study provides novel evidence that mtDNAcn measured in childhood is associated with children’s neurocognitive performance. mtDNAcn may be a marker of healthy child development.