White matter hyperintensities in the deep cerebral venous territory differ between subcortical and cortical 4-repeat tauopathies

Abstract

Background: Progressive supranuclear palsy (PSP) syndromes and corticobasal syndrome (CBS) are atypical parkinsonian disorders resulting from 4-repeat (4R) tauopathies. They target a common network of brain regions, although relative involvement of cortical and subcortical regions differs. White matter hyperintensities (WMHs) are explicit in neurodegenerative disorders, however, little is known about their distribution in 4R-tauopathies.

Objectives: To evaluate the distribution of WMHs in the cortical and subcortical predominant 4R-tauopathies using venous territory-based and the derivative layer designed atlases.

Methods: Ninety-five participants with clinical variants of PSP or CBS were recruited by the Neurodegenerative Research Group, Mayo Clinic, and were classified as cortical (n = 64) or subcortical (n = 31) predominant. WMH volume was calculated for superficial, deep cerebral venous territory, and the periventricular (PV) region. Additionally, a layered atlas was created to assess WMH volume from the lateral ventricles (LV) to the brain surface. WMH volumes, clinical tests, and vascular-relevant histories were compared across groups and to 50 age-matched controls.

Results: Compared to the cortical group, the subcortical group had greater WMHs in the deep venous territory (p = 0.04). The major WMHs in the subcortical group distributed in layers 5-10 (12-30 mm from the LV) (p ≤ 0.01). The subcortical group had more histories of old strokes, chronic kidney disease, and headache.

Conclusions: The distribution of WMHs in the deep cerebral venous territory and the presumed watershed zone suggests that dysfunction of the venous system may play a role in the pathomechanism of 4R-tauopathies, particularly subcortical variants.

Keywords: 4R-tauopathies; Cerebral venous territory; Corticobasal syndrome; Progressive supranuclear palsy; White matter hyperintensities.