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<jats:title>Abstract</jats:title> <jats:p>One third of ischemic stroke patients develop cognitive impairment. It is not known whether topographical secondary neurodegeneration within distributed brain structural covariance networks (SCNs) underlies this cognitive decline. We examined longitudinal changes in SCNs and their relationship to domain-specific cognitive decline in 73 ischemic stroke patients. Patients were scanned with magnetic resonance imaging (MRI) and assessed on five cognitive domains at subacute (3-months) and chronic (1-year) timepoints. Individual-level SCN scores of major cognitive networks were derived from MRI data at each timepoint. We found that distributed degeneration in higher-order cognitive networks was associated with cognitive impairment in subacute stroke. Importantly, faster degradation in these major cognitive SCNs over time was associated with greater decline in attention, memory, and language domains. Our findings suggest that subacute ischemic stroke is associated with degeneration of higher-order structural brain networks and degradation of these networks contribute to individual trajectories of longitudinal domain-specific cognitive dysfunction.</jats:p>

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