Heterogeneity of Cerebral White Matter Lesions and Clinical Correlates in Older Adults

Abstract

Background and Purpose: Cerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences. Methods: Data from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes. Results: Class I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I. Conclusions: We classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.

Heterogeneity of White Matter Hyperintensities in Cognitively Impaired Patients With Cerebral Small Vessel Disease

“…Wardlaw demonstrated the progression of WMH was heterogeneous and the volume of WMH might grow and/or regress, reflected in the change of brain volume, visual scores, and mean diffusivity in WMH ( 7 ). Keun-Hwa Jung showed the variation on clinical symptoms related to WMH, that the periventricular WMH were associated with hypertension and deep WMH were associated with poor sleep quality ( 28 ). However, the heterogeneity of WMH in cognitively impaired patients has not been reported.…”

Fluid-attenuated inversion recovery magnetic resonance imaging textural features as sensitive markers of white matter damage in midlife adults

“… 36 In another study, a combination of WMH features extracted from T 1 -weighted images (among them WMH volume, contrast and lesion position) was used to classify individual into different classes capturing distinct WMH severity. 37 In this latter study, the class with the higher WMH burden comprised participants who were older, with higher blood pressure, higher Framingham risk score and were less active. WMH within that class were less myelinated (T 1 /T 2 mapping) with relatively high contrast, 37 although it needs to be mentioned that the notion that the T 1 /T 2 ratio is a good proxy for myelination has been challenged.…”

“… 37 In this latter study, the class with the higher WMH burden comprised participants who were older, with higher blood pressure, higher Framingham risk score and were less active. WMH within that class were less myelinated (T 1 /T 2 mapping) with relatively high contrast, 37 although it needs to be mentioned that the notion that the T 1 /T 2 ratio is a good proxy for myelination has been challenged. 38 Taken together, characteristics of the intensity profile of WMH might be defining how WMHs impact reaction time, especially in young or middle-aged cohorts with a relatively low WMH burden, where the effect of WMH, as captured by WMH volumetry is not yet prominent in cognition.…”

Show Me Your White Matter, I Will Tell You Who You Are …

“…Interestingly, patterns I and III were inversely associated with sleep quality and the authors posited that sleep disorders might reduce the clearance of fluids and waste within the perivascular spaces that have been associated with enlarged perivascular spaces and WMSA severity. 10 The results of Jung et al 9 suggest that this mechanism may be prevalent in a nonhypertensive subgroup of patients with WMSA.…”

“…In this issue of Stroke, Jung et al 9 explored the heterogeneity of WMSA in an original way. The authors hypothesized that the appearance of WMSA on magnetic resonance imaging is not uniform and differs by pathophysiology.…”