Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy

Abstract

Objective: To determine the rate of progression of white matter lesions and hemorrhages in a cohort with cerebral amyloid angiopathy (CAA).

Methods: The authors analyzed data from 26 patients with possible (3) or probable (23) CAA, diagnosed by the Boston Criteria. Brain maps of white matter hyperintensities, normalized to head size (nWMH), were created by blinded computer-assisted segmentation of MRI images obtained at baseline and after a median follow-up interval of 1.1 year.

Results: There was a substantial nWMH volume increase over the interscan interval (median 0.5 mL/year, interquartile range 0.1 to 2.8, p < 0.001). The median yearly increase, expressed as a percentage of the baseline WMH volume, was 18%. The characteristic most strongly associated with nWMH volume increase was the baseline nWMH volume (r = 0.57, p = 0.002). The volume of nWMH progression was also associated with history of cognitive impairment (median 5.0 mL/year in cognitively impaired subjects vs 0.3 mL/year in cognitively unimpaired, p = 0.02) but not age or hypertension. This association remained present in an analysis stratified by baseline WMH volume. New hemorrhages, including asymptomatic microbleeds, were seen in 46% of subjects. The number of new MRI hemorrhages correlated strongly with baseline nWMH (r = 0.53, p = 0.005) but not with nWMH progression (r = 0.22, p = 0.28).

Conclusions: There is a progressive increase in white matter lesions in subjects with cerebral amyloid angiopathy. The association of white matter lesions with incident lobar hemorrhages suggests that white matter damage may reflect a progressive microangiopathy due to cerebral amyloid angiopathy.

Figure 1

Example of WMH progression. WMH are seen on the baseline (left) and follow-up (right) MRI FLAIR sequences in a 75 year woman with a history of remote left temporal hemorrhage and multiple asymptomatic lobar microbleeds. The results of WMH segmentation (green-colored regions-of-interest) are shown in the bottom panels. During the scan interval of 9 months, WMH increased from 17.8 mL to 23.1 mL (including an increase in WMH around the left occipital horn of the lateral ventricle, arrow). WMH, white matter hyperintensity.

Figure 2

Association of nWMH volume progression with baseline nWMH tertile, by box and whisker plot (the box borders are at the 25^th and 75^th percentiles, the middle bar is at the median, the whiskers extend to 1.5 interquartile ranges, and other values are represented by points). Statistical testing is by Spearman correlation coefficient. nWMH, white matter hyperintensity volume normalized to subject head size.

Figure 3

Association of baseline nWMH with new hemorrhages on MRI, by box and whisker plot (see legend to Figure 2). GRE, gradient-recalled echo MRI sequence; nWMH, white matter hyperintensity volume normalized to subject head size. *Value for number of new hemorrhages was off the scale of the graph (one subject with 78 new hemorrhages).