{"id":"doi:10.1002/alz.71891","kind":"article","title":"Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals","authors":["Zhang S","Roemer-Cassiano SN","Chong JR","Fang T","Li Y","Wang Z","Zeng T","Li X","Deco G","Venketasubramanian N","Zhou JH","Chen CL","Lai MKP","Franzmeier N","Yeo BTT"],"author_count":15,"year":2026,"published":"2026-10-01","venue":"Alzheimer's & dementia : the journal of the Alzheimer's Association","cited_by":0,"doi":"10.1002/alz.71891","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/alz.71891","archive_url":"https://space-kitty.com/papers/doi:10.1002/alz.71891","updated":null,"pmid":"42811946","pmcid":"PMC13624711","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13624711/pdf","abstract":"Introduction Excitation-inhibition (E/I) imbalance has been proposed as an early circuit-level mechanism in Alzheimer's disease (AD), but its relationship to molecular pathology and cognition in humans remains unclear. Methods We integrated biophysical modeling of resting-state functional magnetic resonance imaging with cerebrospinal fluid (CSF) and plasma biomarkers to examine whether E/I ratio links amyloid pathophysiology to memory in non-demented individuals across two cohorts from North America (N = 302; CSF amyloid beta 42 [Aβ42]) and Singapore (N = 240; plasma phosphorylated tau 217 [p-tau217]). Results Elevated E/I ratio was associated with lower CSF Aβ42 and higher plasma p-tau217, with greater sensitivity in sensory-motor regions. In contrast, elevated E/I ratio in association cortices was more strongly related to worse memory function. Mediation analyses indicated E/I ratio partially accounted for the AD biomarker-memory relationship. Discussion E/I imbalance represents an intermediate, systems-level circuit mechanism that links AD pathophysiology to cognitive impairment, offering novel insight into early neurophysiological changes along the AD continuum.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals\" by Zhang S, Roemer-Cassiano SN, Chong JR et al., https://doi.org/10.1002/alz.71891, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}