Higher mitochondrial DNA functional impact score was associated with lower connectivity between dorsal attention and language networks in young adults.
Evidence
An observational neuroimaging analysis in ELSPAC young adults linked mtDNA functional impact score to between-network functional connectivity, with beta = -0.41, p = 0.0007, and AdjR = 0.15 after adjustment for sex, BMI, and substance use.
Caveat
The mediation was only suggestive, with a 95% CI crossing zero, and the observational design cannot show that mitochondrial variants cause worse language-related attention or cognition.
Simplified
Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact () score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. Overall, we conclude that individuals with a greater mtDNA FI score might be at greater risk of experiencing worse attention to relevant linguistic inputs, greater difficulties with speech comprehension, and verbal working memory. 2
Key numbers
-0.41
Decrease in Connectivity
Connectivity between dorsal attention and language networks
0.0007
Significance Level
p-value for the relationship
0.15
Adjusted R-squared
Model fit for the regression analysis
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