ArticleCommunications biology2025
Longitudinal excitation-inhibition balance altered by sex and APOE-ε4.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
2 citing papers in PubMed.
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Sex andInternational journal of molecular sciences · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
Neuronal hyperexcitation affects memory and neural processing across the Alzheimer's disease (AD) cognitive continuum. Levetiracetam, an antiepileptic, shows promise in improving cognitive impairment by restoring the neural excitation/inhibition balance in AD patients. We previously identified a hyper-excitable phenotype in cognitively unimpaired female APOE-ε4 carriers relative to male counterparts cross-sectionally. This sex difference lacks longitudinal validation; however, clarifying the vulnerability of female ε4-carriers could better inform antiepileptic treatment efficacy. Here, we investigated this sex-by-ε4 interaction using a longitudinal design. We used resting-state fMRI and diffusion tensor imaging collected longitudinally from 106 participants who were cognitively unimpaired for at least one scan event but may have been assessed to have clinical dementia ratings corresponding to early mild cognitive impairment over time. By including scan events where participants transitioned to mild cognitive impairment, we modeled the trajectory of the whole-brain excitation-inhibition ratio throughout the preclinical cognitively healthy continuum and extended to early impairment. A linear mixed model revealed a significant three-way interaction among sex, ε4-status, and time, with female ε4-carriers showing a significant hyper-excitable trajectory. These findings suggest a possible pathway for preventative therapy targeting preclinical hyperexcitation in female ε4-carriers.
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Registered trials
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