Aging-Sensitive Networks Within the Human Structural Connectome Are Implicated in Late-Life Cognitive Declines

James W. Madole*, Stuart J. Ritchie, Simon R. Cox, Colin R. Buchanan, Maria Valdés Hernández, Susana Muñoz Maniega, Joanna M. Wardlaw, Mathew A. Harris, Mark E. Bastin, Ian J. Deary, Elliot M. Tucker-Drob

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Background: Aging-related cognitive decline is a primary risk factor for Alzheimer's disease and related dementias. More precise identification of the neurobiological bases of cognitive decline in aging populations may provide critical insights into the precursors of late-life dementias. Methods: Using structural and diffusion brain magnetic resonance imaging data from the UK Biobank (n = 8185; age range, 45–78 years), we examined aging of regional gray matter volumes (nodes) and white matter structural connectivity (edges) within 9 well-characterized networks of interest in the human brain connectome. In the independent Lothian Birth Cohort 1936 (n = 534; all 73 years of age), we tested whether aging-sensitive connectome elements are enriched for key domains of cognitive function before and after controlling for early-life cognitive ability. Results: In the UK Biobank, age differences in individual connectome elements corresponded closely with principal component loadings reflecting connectome-wide integrity (|rnodes| = .420; |redges| = .583), suggesting that connectome aging occurs on broad dimensions of variation in brain architecture. In the Lothian Birth Cohort 1936, composite indices of node integrity were predictive of all domains of cognitive function, whereas composite indices of edge integrity were associated specifically with processing speed. Elements within the central executive network were disproportionately predictive of late-life cognitive function relative to the network's small size. Associations with processing speed and visuospatial ability remained after controlling for childhood cognitive ability. Conclusions: These results implicate global dimensions of variation in the human structural connectome in aging-related cognitive decline. The central executive network may demarcate a constellation of elements that are centrally important to age-related cognitive impairments.

Original languageEnglish
JournalBiological psychiatry
Publication statusAccepted/In press - 1 Jan 2020


  • Brain age
  • Brain networks
  • Cognitive decline
  • Connectomics
  • Diffusion MRI
  • Structural MRI


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