Abstract
BackgroundCerebrovascular 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.MethodsNondemented 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.ResultsLarger 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.ConclusionHigher 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.
Highlights
Cerebrovascular pathology, quantified by white matter lesions (WML), is known to affect cognition in aging, and is associated with an increased risk of dementia
We investigate whether resting state functional connectivity in cognitive control networks, as a proxy of cognitive reserve (CR), plays a role in mitigating the negative effect of cerebrovascular pathology on cognitive performance (Fig. 1, panel A)
Significant clusters were extracted at a cluster-level threshold of p < 0.05, false discovery rate (FDR)-corrected for multiple comparison, and a voxel-level threshold of p < 0.005
Summary
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. Cerebrovascular pathology, as quantified through white matter lesions (WML), is present in more than 50% of the elderly population [1]. WML are known to affect brain structure [2, 3] and cognitive performance [4,5,6,7], and have been associated with an increased risk of stroke and dementia [8]. While the reserve hypothesis has been well established in the context of WML with behavioral measures of CR [9, 15,16,17], the functional mechanisms within neural networks that may convey reserve in cerebrovascular pathology remain to be understood
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