Abstract WP365: Apolipoprotein E ε2 Genotype Influences Post-Stroke Function through EEG Biomarkers

Post-stroke function is influenced by many biological factors, including apolipoprotein E (APOE) genotype. While APOE ε4 may be linked to poorer motor outcomes and altered cortical activity, the effects of ε2 remain understudied. Given that EEG measures relate to post-stroke function, we hypothesized that EEG activity may mediate the relationship between APOE genotype and function. Subacute stroke patients (n=33) were stratified according to APOE genotype (ε2 carriers, non-ε2 carriers). Cortical power in ipsilesional and contralesional primary motor cortex (M1) was extracted from a 3 min resting-state EEG (14±5.3 post-stroke day (PSD)), across five frequency bands (δ, θ, α, β, γ). The GG score, assessing functional status, was collected at admission (PSD 6.7±3.7) and discharge (PSD 24.9±8.3) from inpatient rehabilitation. Change in GG score was expressed as % of admission score (% Δ GG score). ANCOVA tested associations between APOE genotype and cortical activity; Spearman’s correlations assessed links between cortical activity and function; and mediation analyses examined APOE genotype effects on GG scores. P-values were FDR adjusted. Ipsilesional M1 β-power was higher in ε2 carriers ( F (2, 29)=9.89, p =.004; Fig. 1) and correlated positively with discharge GG score (ρ=0.43, p =.013). Mediation showed an indirect APOE effect via ipsilesional M1 β-power, explaining ~16% of discharge GG score (p=0.034). Mediation on the two discharge GG subscores showed no effect specific to either mobility or self-care subscore. ε2 carriers also had lower ipsilesional M1 θ-power ( F (2, 29)=10.16, p =0.003; Fig. 2), which correlated negatively with % Δ GG score (ρ=-0.41, p =0.015). Mediation showed an indirect APOE effect via ipsilesional M1 θ-power, explaining ~53% of % Δ GG score (ACME=48.3, p=0.026). Mediation on the two % Δ GG subscores showed an indirect APOE effect on mobility subscore, via ipsilesional M1 θ-power (p=0.003). Contralesional M1 power was not related to APOE genotype or GG scores. After stroke, APOE ε2 is linked with an EEG profile favorable to function, with increased β- and decreased θ-power ipsilesionally. This matches prior reports linking β-power to better motor status and θ-power to worse motor status. This is the first evidence that EEG activity mediates APOE effects on function and mobility recovery. Clinically, early APOE genotyping combined with EEG may provide useful information for patient stratification and rehabilitation strategies.