Network segregation is associated with processing speed in the cognitively healthy oldest-ol

Abstract

The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain's organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry. We found that the segregation of the association system and the individual networks within the association system [the fronto-parietal network (FPN), cingulo-opercular network (CON) and default mode network (DMN)], has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.

Data availability

Code is available for node creation at https://github.com/Visscher-Lab/MBAR_oldestold_nodes and code and post processed data for statistical analyses and figures is available at https://github.com/Visscher-Lab/MBAR_segregation_paperBecause these data come from a select group of people who have lived to oldest-old ages, making them potentially identifiable, raw data is not available. More detailed data than the post processed data available online can be requested by submitting a request with explanation of intended use of the data to kmv@uab.edu. Requests are reviewed by a committee of principal investigators of the McKnight brain aging registry.

Article and author information

Author details

  1. Sara A Nolin

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    For correspondence
    nolin@musc.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Mary E Faulkner

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Paul Stewart

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Leland L Fleming

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4047-9031
  5. Stacy Merritt

    Miller School of Medicine, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Roxanne F Rezaei

    Evelyn F and William L McKnight Brain Institute, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Prad K Bharadwaj

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Mary Kate Franchetti

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David A Raichlen

    University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Courtney J Jessup

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Lloyd Edwards

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. G Alex Hishaw

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Emily J Van Etten

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Theodore P Trouard

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. David Geldmacher

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Virginia G Wadley

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Noam Alperin

    Miller School of Medicine, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Eric S Porges

    Evelyn F and William L McKnight Brain Institute, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Adam J Woods

    Evelyn F and William L McKnight Brain Institute, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Ron A Cohen

    Evelyn F and William L McKnight Brain Institute, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  21. Bonnie E Levin

    School of Medicine, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  22. Tatjana Rundek

    School of Medicine, University of Miami, Miami, United States
    Competing interests
    The authors declare that no competing interests exist.
  23. Gene E Alexander

    Evelyn F McKnight Brain Institute, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  24. Kristina Visscher

    School of Medicine, University of Alabama at Birmingham, Birmingham, United States
    For correspondence
    kmv@uab.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0737-4024

Funding

Evelyn F. McKnight Brain Research Foundation

  • Ron A Cohen
  • Bonnie E Levin
  • Tatjana Rundek
  • Gene E Alexander
  • Kristina Visscher

National Institute of Health/National institute of Neurological Disorder and Stroke (T32NS061788-12 07/2008)

  • Sara A Nolin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Informed consent was obtained from all participants and approval for the study was received from the Institutional Review Boards at each of the data collection sites including University of Alabama at Birmingham (IRB protocol X160113004), University of Florida (IRB protocol 201300162), University of Miami (IRB protocol 20151783), and University of Arizona (IRB protocol 1601318818).

Copyright

© 2025, Nolin et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 37
    views
  • 15
    downloads
  • 0
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sara A Nolin
  2. Mary E Faulkner
  3. Paul Stewart
  4. Leland L Fleming
  5. Stacy Merritt
  6. Roxanne F Rezaei
  7. Prad K Bharadwaj
  8. Mary Kate Franchetti
  9. David A Raichlen
  10. Courtney J Jessup
  11. Lloyd Edwards
  12. G Alex Hishaw
  13. Emily J Van Etten
  14. Theodore P Trouard
  15. David Geldmacher
  16. Virginia G Wadley
  17. Noam Alperin
  18. Eric S Porges
  19. Adam J Woods
  20. Ron A Cohen
  21. Bonnie E Levin
  22. Tatjana Rundek
  23. Gene E Alexander
  24. Kristina Visscher
(2025)
Network segregation is associated with processing speed in the cognitively healthy oldest-ol
eLife 14:e78076.
https://doi.org/10.7554/eLife.78076

Share this article

https://doi.org/10.7554/eLife.78076

Further reading

    1. Neuroscience
    Lotfi Ferhat, Rabia Soussi ... Michel Khrestchatisky
    Research Article

    Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury, and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to be efficient in pharmacologically induced hypothermia (PIH). Neurotensin (NT), a 13 amino acid neuropeptide that regulates body temperature, interacts with various receptors to mediate its peripheral and central effects. NT induces PIH when administered intracerebrally. However, these effects are not observed if NT is administered peripherally, due to its rapid degradation and poor passage of the blood-brain barrier (BBB). We conjugated NT to peptides that bind the low-density lipoprotein receptor (LDLR) to generate ‘vectorized’ forms of NT with enhanced BBB permeability. We evaluated their effects in epileptic conditions following peripheral administration. One of these conjugates, VH-N412, displayed improved stability, binding potential to both the LDLR and NTSR-1, rodent/human cross-reactivity and improved brain distribution. In a mouse model of kainate (KA)-induced status epilepticus (SE), VH-N412 elicited rapid hypothermia associated with anticonvulsant effects, potent neuroprotection, and reduced hippocampal inflammation. VH-N412 also reduced sprouting of the dentate gyrus mossy fibers and preserved learning and memory skills in the treated mice. In cultured hippocampal neurons, VH-N412 displayed temperature-independent neuroprotective properties. To the best of our knowledge, this is the first report describing the successful treatment of SE with PIH. In all, our results show that vectorized NT may elicit different neuroprotection mechanisms mediated by hypothermia and/or by intrinsic neuroprotective properties.

    1. Neuroscience
    Simon Weiler, Manuel Teichert, Troy W Margrie
    Research Article

    The neocortex comprises anatomically discrete yet interconnected areas that are symmetrically located across the two hemispheres. Determining the logic of these macrocircuits is necessary for understanding high level brain function. Here in mice, we have mapped the areal and laminar organization of the ipsi- and contralateral cortical projection onto the primary visual, somatosensory, and motor cortices. We find that although the ipsilateral hemisphere is the primary source of cortical input, there is substantial contralateral symmetry regarding the relative contribution and areal identity of input. Laminar analysis of these input areas show that excitatory Layer 6 corticocortical cells (L6 CCs) are a major projection pathway within and between the two hemispheres. Analysis of the relative contribution of inputs from supra- (feedforward) and infragranular (feedback) layers reveals that contra-hemispheric projections reflect a dominant feedback organization compared to their ipsi-cortical counterpart. The magnitude of the interhemispheric difference in hierarchy was largest for sensory and motor projection areas compared to frontal, medial, or lateral brain areas due to a proportional increase in input from L6 neurons. L6 CCs therefore not only mediate long-range cortical communication but also reflect its inherent feedback organization.