Disrupted excitation-inhibition balance in cognitively normal individuals at risk of Alzheimer's disease.

Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE-ɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE-ɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population.