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. Satizábal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H. Mosley, Gary A. Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G. Helmer, Steven M. Greenberg, Charles DeCarli, Arvind Caprihan
Abstract
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).