Temporo-frontoparietal hypoconnectivity as a biomarker for isolated language impairment in mild cognitive impairment: A cross-cohort comparison.

Introduction: Whether brain functional connectivity (FC) is consistently disrupted in individuals with mild cognitive impairment (MCI) with isolated language impairment (ilMCI), and its potential to differentiate between MCI subtypes remains uncertain.

Methods: Cross-sectional data from 404 participants in two cohorts (the Chinese Preclinical Alzheimer's Disease Study and the Alzheimer's Disease Neuroimaging Initiative) were analyzed, including neuropsychological tests, resting-state functional magnetic resonance imaging (fMRI), cerebral amyloid positivity, and apolipoprotein E (APOE) status.

Results: Temporo-frontoparietal FC, particularly between the bilateral superior temporal pole and the left inferior frontal/supramarginal gyri, was consistently decreased in ilMCI compared to amnestic MCI (aMCI) and normal controls, which was correlated with semantic impairment. Using mean temporo-frontoparietal FC as a classifier could improve accuracy in identifying ilMCI subgroups with positive cerebral amyloid deposition and APOE risk alleles.

Discussion: Temporal-frontoparietal hypoconnectivity was observed in individuals with ilMCI, which may reflect semantic impairment and serve as a valuable biomarker to indicate potential mechanisms of underlying neuropathology.

Highlights: Temporo-frontoparietal hypoconnectivity was observed in impaired language mild cognitive impairment (ilMCI). Temporo-frontoparietal hypoconnectivity may reflect semantic impairment. Temporo-frontoparietal functional connectivity can classify ilMCI subtypes.