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

Alzheimers Dement (Amst). 2022 Dec 13;14(1):e12362. doi: 10.1002/dad2.12362. eCollection 2022.

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).

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