Decoupling of local activity and interhemispheric connectivity in late mild cognitive impairment: A resting-state...

Mild cognitive impairment (MCI), a high-risk precursor to Alzheimer's disease, progresses through early (EMCI) and late (LMCI) stages. While distinct functional brain alterations between EMCI and LMCI have been reported, differences in regional brain activity and interhemispheric functional connectivity during resting-state remain incompletely characterized. The aim of the study was to systematically assess the differences in resting-state brain functional alterations between the LMCI patients and EMCI patients.

We assessed resting-state functional alterations in EMCI and LMCI using fractional amplitude of low-frequency fluctuations (fALFF) and voxel-mirrored homotopic connectivity (VMHC). Data from 35 EMCI patients, 28 LMCI patients, and 37 individuals with normal cognition were analyzed from the Alzheimer's Disease Neuroimaging Initiative-Phase 2.

Compared to EMCI patients, LMCI patients exhibited increased fALFF in the left inferior temporal gyrus and left precentral gyrus, alongside decreased VMHC in the anterior cerebellar lobe and posterior cingulate cortex. Among MCI patients, Montreal Cognitive Assessment scores showed a significant negative correlation with fALFF in the left inferior temporal gyrus/left precentral gyrus but a significant positive correlation with VMHC in the anterior cerebellar lobe/posterior cingulate cortex.

These findings suggest that elevated regional activity (fALFF) may represent a compensatory mechanism, while reduced interhemispheric connectivity (VMHC) reflects a neuropathological basis underlying progression from EMCI to LMCI. (PsycInfo Database Record (c) 2026 APA, all rights reserved).