Longitudinal deterioration of white-matter integrity: Heterogeneity in the ageing population

Konstantinos Poulakis, Robert I. Reid, Scott A. Przybelski, David S. Knopman, Jonathan Graff-Radford, Val J. Lowe, Michelle M. Mielke, Mary M. Machulda, Clifford R. Jack, Ronald C. Petersen, Eric Westman, Prashanthi Vemuri

Research output: Contribution to journalArticlepeer-review


Deterioration in white-matter health plays a role in cognitive ageing. Our goal was to discern heterogeneity of white-matter tract vulnerability in ageing using longitudinal imaging data (two to five imaging and cognitive assessments per participant) from a population-based sample of 553 elderly participants (age ?60 years). We found that different clusters (healthy white matter, fast white-matter decliners and intermediate white-matter group) were heterogeneous in the spatial distribution of white-matter integrity, systemic health and cognitive trajectories. White-matter health of specific tracts (genu of corpus callosum, posterior corona radiata and anterior internal capsule) informed about cluster assignments. Not surprisingly, brain amyloidosis was not significantly different between clusters. Clusters had differential white-matter tract vulnerability to ageing (commissural fibres > association/brainstem fibres). Identification of vulnerable white-matter tracts is a valuable approach to assessing risk for cognitive decline.

Original languageEnglish (US)
Article numberfcaa238
JournalBrain Communications
Issue number1
StatePublished - 2021


  • Cognitive decline
  • Longitudinal clustering
  • Resilience
  • White-matter microstructure

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience
  • Neurology


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