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Published on: March 19, 2021
Cortical Oscillations as an Endophenotype Mediating ApoE-ε2 Effects on Poststroke Functional Status
Célia Delcamp1,2, Anne Schwarz1,2, Kathie J Ngo1
1Department of Neurology (C.D., A.S., K.J.N., D.Y.W., B.L.F., S.C.C.), David Geffen School of Medicine, University of California, Los Angeles.
Background:
Abundant data link ApoE (apolipoprotein E)-ε2 with favorable outcomes in several neurological settings and in healthy subjects, but studies in relation to stroke outcomes are few. ApoE-ε2 activities are associated with poststroke cortical oscillations, which themselves are correlated with poststroke outcomes. The aim of this cohort study was to determine whether cortical oscillations could represent an endophenotype mediating the effects of ApoE-ε2 on poststroke function.
Methods:
In 33 patients with recent stroke, resting EEG activity (3 minutes), APOE genotype, and functional outcome (GG scores) were measured. ANCOVAs and partial Pearson correlations were performed to validate the prerequisites for mediation analyses, in which EEG cortical power was tested as a mediator of the relationship between APOE-ε2 and functional outcome.
Results:
ApoE-ε2 carriers showed higher ipsilesional beta power and lower ipsilesional theta power, both of which were linked to better functional outcomes. The principal mediation analysis revealed an indirect effect of ApoE-ε2 on functional outcome via ipsilesional M1 beta power (ACME, 14.79 [0.9-34.6], P=0.03), explaining 14% of the average outcome. Exploratory mediation analyses further highlighted an indirect effect of ApoE-ε2 on functional outcome via ipsilesional M1 theta power (ACME, 48.2 [13.3-89.6], P=0.017), explaining 43% of the average outcome. Ipsilesional M1 power in other frequency bands (delta, alpha, gamma) and contralesional M1 power across all frequency bands did not reveal significant mediation effects.
Conclusions:
The mediation analysis results suggests that ApoE-ε2 supports a pro-repair environment, which may translate into more favorable cortical dynamics after stroke. Cortical oscillatory activity may be considered as an endophenotype that mediates the effects of ApoE-ε2 on functional outcome and could potentially be leveraged as a biomarker to develop personalized interventions targeting stroke recovery.
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