Tract-defined regional white matter hyperintensities and memory

Abstract

White matter hyperintensities (WMH) are common radiological findings among older adults and strong predictors of age-related cognitive decline. Recent work has implicated WMH in the pathogenesis and symptom presentation of Alzheimer's disease (AD), which is characterized clinically primarily by a deficit in memory. The severity of WMH volume is typically quantified globally or by lobe, whereas white matter itself is organized by tracts and fiber classes. We derived WMH volumes within white matter tract classes, including association, projection, and commissural tracts, in 519 older adults and tested whether WMH volume within specific fiber classes is related to memory performance. We found that increased association and projection tract defined WMH volumes were related to worse memory function but not to a global cognition summary score that excluded memory. We conclude that macrostructural damage to association and projection tracts, manifesting as WMH, may result in memory decline among older adults.

Keywords: Alzheimer's disease; Memory; White matter fiber tracts; White matter hyperintensities.

Graphical abstract

Fig. 1

Axial slice of a FLAIR sequence with unlabeled white matter hyperintensities (left), and labeled white matter hyperintensities (right).

Fig. 2

The three tract classes using the JHU White Matter Tractography Atlas with corresponding colors (red = commissural, yellow = projection, orange = association) are visualized here, with an overlaid segmented WMH image (in blue) on top.

Fig. 3

A representation of the three classes of white matter tract fibers. Each tract class was 3D rendered in 3D slicer, and displayed next to a cortical hemisphere.

Fig. 4

The interaction plot of Memory Group by WMH Region (F = 3.419, p = .037) illustrating that individuals with lower memory had particularly elevated WMH volume in projection tracts.