MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

Pauline Maillard, Laura J. Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T. Gold, Christopher E. Bauer, Joel H. Kramer, Adam M. Staffaroni, Lara Stables, Danny J.J. Wang, Sudha Seshadri, Claudia L. Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H. Mosley, Gary A. Rosenberg, Baljeet Singh, Herpreet Singh, Kristin SchwabKarl G. Helmer, Steven M. Greenberg, Charles DeCarli, Arvind Caprihan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p = 0.0026). Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

Original languageEnglish (US)
Article numbere12362
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Issue number1
StatePublished - 2022


  • VCID
  • biomarker
  • diffusion tensor imaging
  • free water
  • small vessel disease
  • vascular contributions to cognitive impairment and dementia
  • white matter injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health


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