Late life cognitive control deficits are accentuated by white matter disease burden

Recent evidence suggests that age-related impairments in cognition may be mediated by a specific deficit in the ability to maintain goal-relevant information, a critical component of cognitive control dependent on the dorsolateral prefrontal cortex, although the underlying neural mechanism of these deficits remains unclear. To examine white matter hyperintensities as a neurobiological mechanism of these impairments, older individuals with severe white matter hyperintensity burden, older individuals with low white matter hyperintensity burden, and young adults were assessed in an event-related functional imaging scan while performing the 'AX'-continuous performance task. Individuals with severe white matter hyperintensity burden showed a significant reduction in dorsolateral prefrontal cortex activity during the high cognitive control cue condition relative to the low white matter hyperintensity group and young individuals. Conversely, those with severe white matter hyperintensity burden showed greater activity in rostral anterior cingulate cortex compared to young individuals. These results are consistent with impaired cognitive control and a possible failure to deactivate default-mode regions in these subjects. Additionally, those with severe white matter hyperintensity burden showed reduced functional connectivity between dorsolateral prefrontal cortex and task-relevant brain regions including middle frontal gyrus, and supramarginal gyrus relative to young subjects and those with minimal white matter hyperintensity burden. These results suggest that age-related goal maintenance impairments and associated dorsolateral prefrontal cortex dysfunction may partly reflect incipient white matter disease of interconnected cognitive networks.