ARC connectome separates superagers from Alzheimer's (AUC 0.85)

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) doi.org. 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 doi.org. The result was validated in an independent replication cohort of 143 people doi.org.

Networks and brain age

According to the authors, ARC involved prefrontal, temporal and insular networks and was strongly associated with brain age doi.org. 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 doi.org.

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 doi.org. A genome-wide association analysis identified CLYBL and FRMD6 as novel genetic modulators associated with these divergent aging phenotypes doi.org.

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.

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

Networks and brain age

Follow-up outcomes and genetics

Sources · 1

Read also

CCMB finds two rare MYH7 mutations linked to hypertrophic cardiomyopathy in 160 patients from Telangana