Dynamic Progression of White Matter Hyperintensities in Alzheimer's Disease and Normal Aging: Results from the Sunnybrook Dementia Study

Abstract

Although white matter hyperintensities (WMH), markers of cerebral small vessel disease (SVD), are believed to generally increase over time, some studies have shown sharp decreases after therapeutic intervention, suggesting that WMH progression may be more dynamic than previously thought. Our primary goal was to examine dynamic progression of WMH in a real-world sample of Alzheimer's disease (AD) patients and normal elderly (NC), with varying degrees of SVD. WMH volumes from serial magnetic resonance imaging (MRI; mean = 1.8 years) were measured from NC (n = 44) and AD patients (n = 113) with high and low SVD burden. Dynamic progression for each individual was measured using spatial overlap images to assess shrinkage, growth, and stable WMH volumes. Significant group differences were found for shrinkage (p < 0.001), growth (p < 0.001) and stable (p < 0.001) WMH, where the AD high SVD group showed the largest changes relative to low SVD and NC. Our results suggest spatial progression measured at the individual patient level may be more sensitive to the dynamic nature of WMH.

Keywords: Alzheimer’s disease; aging; dementia; longitudinal progression; small vessel disease; white matter hyperintensities.

Figure 1

Baseline (left) and follow-up (right) MRIs were half transformed into intermediate space (middle) using linear registration (FLIRT). Shrinking (yellow), growing (blue) and stable (purple) white matter hyperintensities (WMH) spatial segmentations are displayed in intermediate space for a 71 year old female with Alzheimer’s disease (AD). Net change in WMH total volume from baseline to follow-up was −1.5 cc. However, when considering dynamic progression based on spatial information: shrinking WMH = −8.2 cc, growing WMH = +6.3 cc, and stable WMH = 32.4 cc.

Figure 2

Two year ventricular expansion in a 60 year old man living with AD. Baseline vCSF = 83.6 cc, follow-up vCSF = 119.0 cc. Green indicates baseline vCSF voxels, pink indicates follow-up (right) and growth (middle). WMH within vCSF growth regions were subsequently removed to account for ventricular expansion.

Figure 3

Dynamic changes in WMH volume over a mean interscan interval (ISI) of 2 years for NC, AD low small vessel disease (SVD), and AD high SVD groups. P values represent significant differences between all diagnostic groups, based on estimated marginal means, accounting for baseline age, years of education, mini mental state exam (MMSE), and vCSF.