They are indicative of vascular pathology but represent a mixture of microstructural tissue alterations that is highly variable between individuals. To better understand these alterations, we leveraged the signal of different MRI contrasts sampled within WMHs, which have differential sensitivity to microstructural properties. We demonstrated that the correlations between WMH signal measures were variable, suggesting that they are likely influenced by different microstructural properties.
These findings may have implications in determining the reversibility of WMHs and potential efficacy of cardio- and cerebrovascular treatments. WMHs are commonly detected in the elderly and considered to be markers of small vessel disease. However, ex vivo histological examinations of microstructural alterations within WMHs report heterogeneous tissue alterations, 15 , 16 with demyelination, axonal loss, and inflammation being present at various degrees or even absent.
In this study, we aimed to determine which WMH microstructural measures would be useful in assessing the severity of tissue damage. We measured six different MRI signals within WMHs in a sample of cognitively intact elderly and of participants spanning the AD spectrum from high-risk to clinically diagnosed AD dementia totaling subjects. Using univariate and multivariate methods and two different white matter parcellations, we examined the relationships among WMH measures and assessed the sensitivity of signal trends to WMH-specific tissue deterioration by comparing the age- and disease-related trends of the signal between WMH and normal-appearing white matter NAWM.
We further related WMH measures to multiple types of clinical variables cortical and global atrophy, cognition, demographic and group differences, and cardiovascular risk factors , with the rationale that signal measures sensitive to clinically-meaningful variations in underlying WMH tissue alterations would be related to adverse neurobiological and clinical outcomes. Our methodology is outlined in Fig. Signed informed consent from all participants was obtained and the research protocols were approved by the Research Ethics Board of the Douglas Mental Health University Institute, Montreal, Canada.
Summary statistics of demographic and cognitive variables before and after quality control QC procedures see Supplementary Methods 1 are detailed in Table 1 both cohorts combined. Summary statistics of demographic and cognitive variables before and after quality control QC procedures.
