Skip to content
DraconiticResearch
Search Sources API
197,783 studies31 sourcesUpdated 7 min ago
Peer-reviewedCC BY-NC 4.0Science Advances

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

  • Kanhao Zhao1,2,3
  • Hua Xie4
  • Gregory A. Fonzo5
  • Nancy B. Carlisle6
  • Tovia Jacobs7
  • Ricardo S. Osorio8
  • Arpana Church3
  • Feng Vankee Lin1,9,10
  • Yu Zhang1,9,10
  • Alzheimer’s Disease Neuroimaging Initiative
10 affiliations
  1. 1Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  2. 2Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.
  3. 3Goodman-Luskin Microbiome Center, Vache and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  4. 4Center for Neuroscience Research, Children’s National Hospital, Washington, DC, USA.
  5. 5Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
  6. 6Department of Psychology, Lehigh University, Bethlehem, PA, USA.
  7. 7Penn State College of Medicine, Hershey, PA, USA.
  8. 8Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
  9. 9Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
  10. 10Stanford Institute for Human-Centered Artificial Intelligence, Stanford, CA, USA.
Read full textDOICite

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.

Related

  1. Sex-dependent effects of chronic stress during adolescence on cognitive bias and functional connectome in young adult rats
    Twain Dai, Liz Jaeschke-Angi, Marissa Penrose-Menz +2
    Translational PsychiatryPeer-reviewedCC BY-NC-ND 4.0Full textNeuroscienceCrossref
  2. Discovering Subtypes of Neurodegenerative Progression with a Scalable Connectome-Constrained Dynamic Model
    Daniel Semchin, Emile d'Angremont, Hao Ding +6
    arXivPreprintarXiv licenceFull textBioinformatics & computational biologyNeurosciencearXiv
  3. Identifying Neurophysiological Subtypes in Clinical High Risk for Psychosis Using Functional Connectome Profiling
    Guoliang Hou, Jiayu Feng, Yulin Wang +1
    Schizophrenia BulletinPeer-reviewedPublisher termsFull textNeurosciencePMC
  4. Exploring the spatio-temporal functional connectome in PTSD: evidence of static and dynamic network alterations
    Jing Shang, Minlan Yuan, Xian Mo +5
    BMC PsychiatryPeer-reviewedCC BY 4.0Full textNeurosciencePMC
  5. Connectivity allometry is a robust organizing principle of the human functional connectome
    C. Wu, X. Qiu, J. Li +3
    bioRxivPreprintCC BYFull textNeurosciencebioRxiv

Cite

BibTeXRIS
BibTeX
@article{zhao2026functional,
  title = {{A functional connectome identifies vulnerability to cognitive decline and Alzheimer’s disease progression}},
  author = {Kanhao Zhao and Hua Xie and Gregory A. Fonzo and Nancy B. Carlisle and Tovia Jacobs and Ricardo S. Osorio and Arpana Church and Feng Vankee Lin and Yu Zhang and Alzheimer’s Disease Neuroimaging Initiative},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aed9351},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aed9351},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - A functional connectome identifies vulnerability to cognitive decline and Alzheimer’s disease progression
AU  - Kanhao Zhao
AU  - Hua Xie
AU  - Gregory A. Fonzo
AU  - Nancy B. Carlisle
AU  - Tovia Jacobs
AU  - Ricardo S. Osorio
AU  - Arpana Church
AU  - Feng Vankee Lin
AU  - Yu Zhang
AU  - Alzheimer’s Disease Neuroimaging Initiative
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aed9351
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aed9351
AB  - 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.
SN  - 2375-2548
ER  -