Abstract

There is well-documented evidence of brain network differences between individuals with Alzheimer’s disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitudinal ADNI data on the whole brain to jointly compute the brain network at baseline and one-year using a state of the art approach that pools information across both time points to yield distinct visit-specific networks for the AD and HC cohorts, resulting in more accurate inferences. We perform a multiscale comparison of the AD and HC networks in terms of global network metrics as well as at the more granular level of resting state networks defined under a whole brain parcellation. Our analysis illustrates a decrease in small-worldedness in the AD group at both the time points and also identifies more local network features and hub nodes that are disrupted due to the progression of AD. We also obtain high reproducibility of the HC network across visits. On the other hand, a separate estimation of the networks at each visit using standard graphical approaches reveals fewer meaningful differences and lower reproducibility.

Highlights

  • Alzheimer’s disease (AD) is one of the most common forms of dementia

  • We focused on global efficiency (GE), local efficiency (LE), characteristic path length (CPL), mean clustering coefficient (MCC), and small-worldedness, which were calculated based on the estimated adjacency matrices from Bayesian joint network learning (BJNL)

  • In comparison to 40.1% and 40.0% connections that were contained within resting state networks (RSNs) for the healthy controls (HC) network at baseline and one-year, only 30.3% and 30.3% of the connections were contained within RSNs for the AD network at baseline and one-year

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Summary

Introduction

Alzheimer’s disease (AD) is one of the most common forms of dementia. An increasing emphasis is being placed on identifying biomarkers for the detection of AD at an early or pre-clinical stage in hopes of limiting the neuronal damage caused by AD. Graph-theoretical studies of functional connectivity in HC and AD patients typically estimate the brain network separately for each individual or cohort and examine differences in these networks to identify brain regions with disrupted connectivity in AD patients[5,6]. These differences can be investigated at different levels of granularity, such as at the edge level, node level, or at the level of global or local network metrics. Compared to cross-sectional data, a key advantage in longitudinal fMRI studies is that one can potentially use state of the art statistical methods to jointly estimate the brain networks over multiple visits by pooling information across visits. The approach by[26] uses a regression based model that is unable to produce a positive definite precision matrix which is key to quantifying the edge strengths

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