A functional connectome identifies vulnerability to cognitive decline and Alzheimer's disease progression
Related Experiment Video
Updated: Nov 6, 2026

Modeling the Functional Network for Spatial Navigation in the Human Brain
Published on: October 13, 2023
Kanhao Zhao1,2,3, Hua Xie4, Gregory A Fonzo5
1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:
Identifying the neurobiological basis of cognitive vulnerability is essential for preventing Alzheimer's disease (AD). We derived the Alzheimer's Resilience-Vulnerability Connectome (ARC) by contrasting SuperAgers (SA), an extreme phenotype of preserved late-life memory, with AD using resting-state fMRI. ARC distinguished SA from AD in a discovery cohort (N = 290; AUC = 0.85) and replicated independently (N = 143), involving prefrontal, temporal, and insular networks and associating with brain age. Applied to cognitively unimpaired adults (discovery: N = 818; replication: N = 497), ARC-based subtyping revealed SA-like and AD-like subgroups with comparable baseline cognition but divergent longitudinal trajectories. AD-like individuals exhibited faster cognitive decline, greater amyloid-β accumulation, and higher AD conversion risk. Exploratory GWAS nominated CLYBL and FRMD6 as candidate novel loci associated with the subtype difference. These findings suggest that ARC captures a continuous connectomic dimension of cognitive aging spanning SA, cognitively typical aging, and AD, highlighting the potential of functional connectomic variation for early risk stratification in AD.
More Related Videos
08:43Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
09:38Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Related Concept Videos
Alzheimer Disease ll: Pathophysiology
Dementia l: Introduction
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease l: Introduction
Functional Brain Systems: Limbic System
Alzheimer's Disease: Treatment