Equalization of Brain State Occupancy Accompanies Cognitive Impairment in Cerebral Small Vessel Disease


BACKGROUND: Cognitive impairment is a hallmark of cerebral small vessel disease (cSVD). Functional magnetic resonance imaging has highlighted connections between patterns of brain activity and variability in behavior. We aimed to characterize the associations between imaging markers of cSVD, dynamic connectivity, and cognitive impairment.

METHODS: We obtained magnetic resonance imaging and clinical data from the population-based Hamburg City Health Study. cSVD was quantified by white matter hyperintensities and peak-width of skeletonized mean diffusivity (PSMD). Resting-state blood oxygen level-dependent signals were clustered into discrete brain states, for which fractional occupancies (%) and dwell times (seconds) were computed. Cognition in multiple domains was assessed using validated tests. Regression analysis was used to quantify associations between white matter damage, spatial coactivation patterns, and cognitive function.

RESULTS: Data were available for 979 participants (ages 45-74 years, median white matter hyperintensity volume 0.96 mL). Clustering identified five brain states with the most time spent in states characterized by activation (+) or suppression (-) of the default mode network (DMN) (fractional occupancy: DMN+ = 25.1 ± 7.2%, DMN- = 25.5 ± 7.2%). Every 4.7-fold increase in white matter hyperintensity volume was associated with a 0.95-times reduction of the odds of occupying DMN+ or DMN-. Time spent in DMN-related brain states was associated with executive function.

CONCLUSIONS: Associations between white matter damage, whole-brain spatial coactivation patterns, and cognition suggest equalization of time spent in different brain states as a marker for cSVD-associated cognitive decline. Reduced gradients between brain states in association with brain damage and cognitive impairment reflect the dedifferentiation hypothesis of neurocognitive aging in a network-theoretical context.

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StatusVeröffentlicht - 01.10.2022

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