Brain atrophy and clinical diagnosis independently predict default mode network failure across the Alzheimer's disease continuum.

INTRODUCTION

This study examined the link between default mode network (DMN) functional connectivity, cerebral small vessel disease (CSVD), brain atrophy, and plasma Alzheimer's disease (AD) biomarkers.

METHODS

We analyzed the Alzheimer's Disease Neuroimaging Initiative database (N = 279), examining the relationships between DMN functional integrity (network failure quotient [NFQ]), gray and white matter fractions (GMF, WMF), white matter hyperintensities (WMHs), plasma phosphorylated tau (p-tau)217 and amyloid beta (Aβ)42/Aβ40 ratio, and clinical assessments. Statistical associations were tested using one-way analysis of variance and univariate and multivariate regression models.

RESULTS

The AD group showed increased NFQ values (P < 0.001). Significant univariate associations were found between NFQ and WMH, gray and white matter atrophy, Aβ ratio, and p-tau217 (P < 0.05). Atrophy markers (GMF, WMF) and AD diagnosis were the only independent predictors of NFQ in multivariate models (P < 0.05).

DISCUSSION: Our study identifies markers of brain atrophy as independent predictors of DMN failure, unlike AD plasma biomarkers and magnetic resonance imaging markers of CSVD.