Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy
Rasing, Ingeborg, Vlegels, Naomi, Schipper, Manon R., Voigt, Sabine, Koemans, Emma A., Kaushik, Kanishk, van Dort, Rosemarie, van Harten, Thijs W., De Luca, Alberto, van Etten, Ellis S., van Zwet, Erik W., van Buchem, Mark A., Middelkoop, Huub A.M., Biessels, Geert Jan, Terwindt, Gisela M., van Osch, Matthias J.P., van Walderveen, Marianne A.A., Wermer, Marieke J.H.
DOI: https://doi.org/10.1177/0271678X241261771
Journal of Cerebral Blood Flow and Metabolism 44 (11), p. 1253-1261
Abstract
Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77–9.50]mm2/s × 10−4) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm2/s × 10−4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16–0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08–0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22–0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13–0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = −0.42 [−0.69–0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.