Discrete white matter hyperintensity (WMH) growth quantification is superior to measurements of total longitudinal WMH volume change: implications for clinical trials in VCID

AbstractBackgroundSmall vessel ischemic disease (SVID) is a major risk factor for late‐life cognitive impairment and dementia (VCID). White matter hyperintensities (WMH) are a SVID biomarker that can be detected on MRI FLAIR imaging. Prior studies show dynamic change in WMH volumes that increase and decrease within subjects over time. We reported a method to quantify discrete WMH volume growth and regression in individuals over one‐year with instrumental validation performed within the MarkVCID consortium. The present study provides preliminary evidence for the clinical relevance of this methodology.Method3D MRI T1‐weighted and FLAIR images at baseline and 12‐month follow‐up visits for sixty‐one participants (mean age 74 ± 5.9 years, 31 women) were analyzed. The Stroop test was administered using the CANS‐MCI computerized battery. WMH growth and regression were quantified for all participants. A linear regression model was used to assess the association of dynamic WMH changes with Stroop performance.ResultWMH growth, but not regression or total WMH volume changes was associated with Stroop performance at the 12‐months (β = ‐0.24, P = 0.02) after controlling for sex, and age (graph).ConclusionThese data show that WMH growth, but not regression or total WMH volume change, was associated with a decline in performance on the Stroop test over12‐months. These findings highlight the importance of studying dynamic, within subject, WMH growth and regression rather than solely focusing on longitudinal change in total WMH volume measurements. Measurement of WMH growth may help reduce sample sizes, facilitate clinical trial conduct, and optimize the potential to identify interventions intended to mitigate SVID contributions to VCID.