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April 1, 2026Journal of Alzheimer s Disease0 citations

Longitudinal trajectories of amyloid-β-driven alterations in voxel-mirrored homotopic connectivity and cognitive decline in mild cognitive impairment

Key Points

This research aims to analyze the effects of amyloid-β on homotopic connectivity and cognitive decline in individuals with mild cognitive impairment over time.
Eighty-three participants from ADNI were assessed over two years, with baseline and follow-up evaluations.
Participants were classified as Aβ-positive or negative based on 18F-AV45 PET imaging.
Voxel-mirrored homotopic connectivity (VMHC) and corpus-callosum volume comparisons were conducted using ANOVA.
Spearman correlations linked VMHC to cognitive performance and cerebrospinal fluid biomarkers.
Linear mixed-effects models evaluated group-by-time interactions.
MCI-Aβ- showed lower VMHC in specific brain regions compared to MCI-Aβ+.
MCI-Aβ+ had greater reductions in VMHC, linking to poorer cognitive outcomes and abnormal CSF profiles.
VMHC changes inversely correlated with cognitive performance decline over two years.
Distinct VMHC trajectories were observed, indicating the relationship between amyloid burden and interhemispheric connectivity loss.

Abstract

BackgroundAmyloid-β (Aβ) deposition in mild cognitive impairment (MCI) disrupts interhemispheric homotopic connectivity, yet its longitudinal course is unclear.ObjectiveWe aim to characterize the longitudinal decay of voxel-mirrored homotopic connectivity (VMHC) in MCI patients, elucidate underlying Aβ-associated mechanisms, and link these processes to cognitive decline.MethodsEighty-three ADNI participants (60 MCI, 23 cognitively normal CN) underwent baseline and two-year follow-up. MCI cases were stratified by 18F-AV45 PET into Aβ-positive (MCI-Aβ+, n = 44) and Aβ-negative (MCI-Aβ-, n = 16) subgroups. VMHC and corpus-callosum volume were compared across groups (ANOVA). Spearman correlations linked regional VMHC to cognition, cerebrospinal fluid (CSF) biomarkers, and callosal volume. Linear mixed-effects models tested group-by-time interactions; two-year VMHC change was related to parallel cognitive decline.ResultsAt baseline, MCI-Aβ- patients showed lower VMHC in the fusiform and postcentral gyri, whereas MCI-Aβ+ patients exhibited additional reductions in the precuneus, superior frontal gyrus, cerebellum, and superior occipital gyrus. Lower VMHC correlated with poorer cognition, corpus-callosum atrophy, and abnormal CSF profiles; callosal volume itself did not differ between groups. Longitudinally, MCI-Aβ+ participants exhibited a slower VMHC decline across the posterior cingulate, cerebellum and thalamus. Two-year cumulative change in VMHC inversely correlated with change in cognitive performance.ConclusionsAβ burden shapes distinct trajectories of interhemispheric connectivity loss in MCI. VMHC decline tracks multi-domain cognitive deterioration and may serve as a biomarker of progression toward Alzheimer's disease.

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