Peer-reviewedCC BY 4.0Nature Neuroscience
Different functional connectivity gradients reflect aging and Alzheimer’s disease
15 affiliations
- 1Department of Clinical Sciences Malmö, SciLifeLab, Lund University, Lund, Sweden
- 2Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
- 3Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 4Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- 5Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden
- 6Penn Lifespan Informatics and Neuroimaging Center, Philadelphia, PA USA
- 7Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA USA
- 8Penn-Children’s Hospital of Philadelphia Lifespan Brain Institute, University of Pennsylvania, Philadelphia, PA USA
- 9Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA
- 10Diagnostic Radiology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- 11Image and Function, Skåne University Hospital, Lund, Sweden
- 12Department of Neuroscience, University of California, Berkeley, Berkeley, CA USA
- 13Memory Clinic, Skåne University Hospital, Malmö, Sweden
- 14Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
- 15Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands
Abstract
Aging and Alzheimer’s disease (AD) are accompanied by alterations to large-scale communication patterns in the brain, which can be tracked in vivo using functional connectivity. The location, direction and relevance of these changes remain widely debated, although they are rarely studied in the context of whole-cortex communication dynamics. Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer’s Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes associated with aging and AD are strongly aligned with separate fundamental axes of hierarchical brain communication. Early accumulation of AD pathology and subsequent cognitive decline are both linked to functional change along the sensory–association axis. Meanwhile, age-related functional changes occur along the representation–executive axis consistently throughout the adult lifespan. These findings together suggest that both AD and aging alter major but orthogonal functional pathways in the brain. More broadly, our findings position whole-brain connectivity dynamics as a unifying framework for interpreting functional changes across the adult lifespan.
Related
- Emergence of long- and short-range functional connectivity parallels the development of neonatal brain gradients
- Somatotopic functional connectivity gradients in the monkey and human striatum.
- Intervention on modifiable lifestyle and physiological factors via variational autoencoder reveals changes in functional connectivity-mediated risk for Alzheimer’s disease
- Research on dynamic functional connectivity and graph theoretic features of different motor subtypes in Parkinson’s disease based on ICA
- Ongoing thoughts at rest reflect functional brain organization and behaviour
BibTeX
@article{rittmo2026different,
title = {{Different functional connectivity gradients reflect aging and Alzheimer’s disease}},
author = {Jonathan Rittmo and Nicolai Franzmeier and Olof Strandberg and Léa Chauveau and Theodore D. Satterthwaite and Laura E. M. Wisse and Nicola Spotorno and Harry H. Behjat and Amir Dehsarvi and Danielle van Westen and Toomas Erik Anijärv and Susan M. Landau and Susan M. Landau and Susan M. Landau and Sebastian Palmqvist and Shorena Janelidze and Erik Stomrud and Rik Ossenkoppele and Niklas Mattsson-Carlgren and Oskar Hansson and Jacob W. Vogel},
journal = {Nature Neuroscience},
year = {2026},
month = oct,
doi = {10.1038/s41593-026-02402-0},
url = {https://doi.org/10.1038/s41593-026-02402-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Different functional connectivity gradients reflect aging and Alzheimer’s disease
AU - Jonathan Rittmo
AU - Nicolai Franzmeier
AU - Olof Strandberg
AU - Léa Chauveau
AU - Theodore D. Satterthwaite
AU - Laura E. M. Wisse
AU - Nicola Spotorno
AU - Harry H. Behjat
AU - Amir Dehsarvi
AU - Danielle van Westen
AU - Toomas Erik Anijärv
AU - Susan M. Landau
AU - Susan M. Landau
AU - Susan M. Landau
AU - Sebastian Palmqvist
AU - Shorena Janelidze
AU - Erik Stomrud
AU - Rik Ossenkoppele
AU - Niklas Mattsson-Carlgren
AU - Oskar Hansson
AU - Jacob W. Vogel
PY - 2026
DA - 2026/10/01
JO - Nature Neuroscience
DO - 10.1038/s41593-026-02402-0
UR - https://doi.org/10.1038/s41593-026-02402-0
AB - Aging and Alzheimer’s disease (AD) are accompanied by alterations to large-scale communication patterns in the brain, which can be tracked in vivo using functional connectivity. The location, direction and relevance of these changes remain widely debated, although they are rarely studied in the context of whole-cortex communication dynamics. Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer’s Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes associated with aging and AD are strongly aligned with separate fundamental axes of hierarchical brain communication. Early accumulation of AD pathology and subsequent cognitive decline are both linked to functional change along the sensory–association axis. Meanwhile, age-related functional changes occur along the representation–executive axis consistently throughout the adult lifespan. These findings together suggest that both AD and aging alter major but orthogonal functional pathways in the brain. More broadly, our findings position whole-brain connectivity dynamics as a unifying framework for interpreting functional changes across the adult lifespan.
SN - 1097-6256
SN - 1546-1726
ER -