Functional connectivity in cognitive control networks mitigates the impact of white matter lesions in the elderly

Abstract

Background: Cerebrovascular pathology, quantified by white matter lesions (WML), is known to affect cognition in aging, and is associated with an increased risk of dementia. The present study aimed to investigate whether higher functional connectivity in cognitive control networks mitigates the detrimental effect of WML on cognition. Methods: Nondemented older participants (≥ 50 years; n = 230) underwent cognitive evaluation, fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and resting state functional magnetic resonance imaging (fMRI). Total WML volumes were quantified algorithmically. Functional connectivity was assessed in preselected higher-order resting state networks, namely the fronto-parietal, the salience, and the default mode network, using global and local measures. Latent moderated structural equations modeling examined direct and interactive relationships between WML volumes, functional connectivity, and cognition. Results: Larger WML volumes were associated with worse cognition, having a greater impact on executive functions (β = -0.37, p < 0.01) than on memory (β = -0.22, p < 0.01). Higher global functional connectivity in the fronto-parietal network and higher local connectivity between the salience network and medial frontal cortex significantly mitigated the impact of WML on executive functions, (unstandardized coefficients: b = 2.39, p = 0.01; b = 3.92, p = 0.01) but not on memory (b = -5.01, p = 0.51, b = 2.01, p = 0.07, respectively). No such effects were detected for the default mode network. Conclusion: Higher functional connectivity in fronto-parietal and salience networks may protect against detrimental effects of WML on executive functions, the cognitive domain that was predominantly affected by cerebrovascular pathology. These results highlight the crucial role of cognitive control networks as a neural substrate of cognitive reserve in older individuals.