# Brain connectivity signature ARC separates superagers from Alzheimer's patients with AUC 0.85 in fMRI study

- Published: 2026-11-05 18:06 UTC
- Section: Life & Health › Medicine
- Tags: Alzheimer's-resilient connectome, superagers, resting-state fMRI, functional connectivity, cognitive decline, amyloid-β accumulation, mild cognitive impairment, brain age, CLYBL FRMD6, Alzheimer's biomarker
- URL: https://realtech.media/news/rt-007e38c35a484bf28c06dafa_brain_connectivity_signature/

**Researchers used resting-state fMRI to define a connectivity signature that also split cognitively unimpaired adults into subgroups with different rates of cognitive decline.**

![Brain connectivity signature ARC separates superagers from Alzheimer's patients with AUC 0.85 in fMRI study](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/b05c1dcfd5fd3f4b.jpg)
*Bobjgalindo, Wikimedia Commons, CC BY-SA 4.0*

A research team reported in Science Advances a functional connectivity signature, termed Alzheimer's-resilient connectome (ARC), that differentiates superagers from age-matched patients with Alzheimer's disease (AD) [1]. Superagers are older adults who maintain youthful memory into late life. The signature was derived from resting-state fMRI in a discovery cohort of 290 people using machine learning classifiers, which distinguished superagers from AD with AUC = 0.85 [1]. The result was validated in an independent replication cohort of 143 people [1].

## Networks and brain age

According to the authors, ARC involved prefrontal, temporal and insular networks and was strongly associated with brain age [1]. The team then applied it to cognitively unimpaired adults: 818 in the discovery cohort and 497 in the replication cohort. ARC-based subtyping revealed superager-like and AD-like subgroups. At baseline they had similar cognitive performance, but their longitudinal trajectories diverged markedly [1].

## Follow-up outcomes and genetics

Superager-like individuals showed slower cognitive decline and reduced amyloid-β accumulation. They also had a lower risk of conversion to mild cognitive impairment and AD [1]. A genome-wide association analysis identified CLYBL and FRMD6 as novel genetic modulators associated with these divergent aging phenotypes [1].

The authors describe ARC as a sensitive and generalizable biomarker of resilience that could enable early risk stratification. The work is an analysis of cohort data; no intervention was tested.

## Sources

1. [Science Advances](https://doi.org/10.1126/sciadv.aed9351)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-007e38c35a484bf28c06dafa_brain_connectivity_signature/