A functional connectome identifies vulnerability to cognitive decline and Alzheimer's disease progression.

The Alzheimer's Resilience-Vulnerability Connectome (ARC) distinguishes SuperAgers from Alzheimer’s disease with AUC = 0.85 in a discovery cohort (N = 290) using resting-state fMRI.

• Why it matters: Cognitive vulnerability is a key target for preventing Alzheimer’s disease, but the neurobiological basis linking preserved memory to AD progression remains unclear.
• What they did: ARC was built by contrasting SuperAgers (SA) with AD in resting-state fMRI, then replicated independently (N = 143) and applied to cognitively unimpaired adults (N = 818; N = 497) for subtype discovery.
• The result: ARC-defined AD-like subgroups showed faster cognitive decline, greater amyloid-β accumulation, and higher AD conversion risk, and exploratory GWAS nominated CLYBL and FRMD6 as candidate loci.

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