White matter hyperintensities and normal-appearing white matter integrity in the aging brain

Susana Muñoz Maniega,Maria C Valdés Hernández,Jonathan D Clayden,Natalie A Royle,Catherine Murray,Zoe Morris,Benjamin S Aribisala,Alan J Gow,John M Starr,Mark E Bastin,Ian J Deary,Joanna M Wardlaw

doi:10.1016/j.neurobiolaging.2014.07.048

Abstract

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10−9 m2s−1 (area under curve, 0.982; 95% CI, 0.975–0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.

Highlights

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging (MRI) scans of healthy elderly individuals and are important features associated with impaired cognitive function in later life (Deary et al, 2003)
Values of Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower whereas mean diffusivity (MD) and T1 were significantly higher in WMH than normal-appearing white matter (NAWM) (p < 0.0001), with MD providing the largest difference between the two tissue classes (Fig. 2 and Table 2); all effect sizes were large
Results from the four imaging biomarkers used in the present study indicate that WMH have reduced white matter integrity compared with NAWM, with the integrity of NAWM, in turn, affected by the severity of these lesions even after accounting for age, gender, and self-reported vascular risk factors (VRF)

Summary

Introduction

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging (MRI) scans of healthy elderly individuals and are important features associated with impaired cognitive function in later life (Deary et al, 2003). These lesions appear as hyperintensities in the. Structural changes in NAWM in people with WMH versus those without have been reported using a variety of imaging modalities, including structural, vascular, and metabolic MRI (Firbank et al, 2003; Maillard et al, 2011; Uh et al, 2010), these changes are still to be fully characterized

Methods

Results

Conclusion