Multilayer brain connectivity and long-term cognitive changes in individuals at risk for Alzheimer's disease

Abstract

Background

Among aging individuals, some develop Alzheimer's disease (AD) while others remain cognitively stable. Understanding how structural and functional brain changes interact, could clarify this heterogeneity particularly among individuals at increased risk for AD.

Objective

This study aims to explore how structure-function connectivity changes relate to subsequent long-term cognitive trajectories in older adults with SMC and varying amyloid burden.

Methods

We analyzed data from the INSIGHT-preAD cohort, which includes older individuals with subjective cognitive complaints followed neuropsychologically over five years. Multiplex connectome integrating resting-state EEG functional connectivity and diffusion-weighted imaging-based structural connectivity was used to characterize brain network organization. We computed the multiplex participation coefficient (PC) as an index of structure-function similarity and examined its association with individual cognitive trajectories across the follow-up period.

Results

Significant differences in multiplex connectivity were observed among amyloid positive participants who later progressed to AD compared to amyloid positive stable (e.g., non-progressors) and amyloid negative controls. Specifically, higher PC values in the delta band were observed in amyloid positive individuals who later developed AD. This pattern, particularly within the default mode network, was associated with subsequent cognitive decline suggesting that delta band structure-function similarity may represent a potential candidate marker of cognitive vulnerability and progression in AD.

Conclusions

Most studies investigating AD have primarily examined functional or structural connectivity separately. By integrating both modalities using a multiplex approach, our study provides interesting preliminary evidence that structure-function connectivity may capture network-level changes associated with cognitive trajectories along AD continuum.