Introduction: In middle age, declines in executive functioning (EF) are associated with decrements in the quality and/or quantity of white and grey matter. Recruitment of homologous regions has been identified as a compensatory mechanism for cognitive decline in later middle age, however research into neural substrates of EF has yet to be guided by dedifferentiation models. We hypothesized that frontal-parietal grey matter volume, interhemispheric white matter and intrahemispheric white matter fractional anisotropy (FA) will be predictive of EF. Further, we hypothesized that the comparative association between interhemispheric white matter and EF will increase with age, because of compensatory recruitment. Methods: Neurocognitive test data, DTI, and T1 MPRAGE scans (n = 444) were obtained from the NKI-Rockland Sample. Structural equation modeling was used to examine the relationship between age, EF, interhemispheric white matter (forceps minor; FM), intrahemispheric white matter (superior longitudinal fasciculus; SLF), and a frontal-parietal grey matter network. EF and grey matter were modelled as latent variables, with EF examined as the criterion. Additionally, a subsample of participants aged 55-85 (n = 168) was analyzed to examine the influence of age related compensatory mechanisms. Results: There was a significant relationship between FM, grey matter, and EF, which was fully mediated by age. There was a significant relationship between SLF and EF, which was not mediated by age. For older adults, only the age-mediated pathway from FM to EF was significant. Discussion: Using structural imaging data, support was found for age-related interhemispheric mechanisms of compensation, but not intrahemispheric mechanisms.

On the Impact of Interhemispheric White Matter: Age, Executive Functioning, and Dedifferentiation in the Frontal Lobes