Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy

Journal of Cerebral Blood Flow & Metabolism, vol. 44, pp. 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]mm 2 /s × 10 −4 ) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm 2 /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.

Authors 17

1. Ingeborg Rasing corresponding Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

2. Naomi Vlegels

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

3. Sabine Voigt Aachen Department of Neurology, Leiden University Medical Center (LUMC) Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

   Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

4. Emma A. Koemans Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

5. Kanishk Kaushik Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

6. Rosemarie van Dort Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

7. Thijs W. van Harten Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

8. Alberto De Luca

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

   Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

9. Ellis S. van Etten Aachen Department of Neurology, Leiden University Medical Center (LUMC)

   Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

10. Erik W. van Zwet Aachen Department of Biostatistics, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherland

11. Mark A. van Buchem Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

12. Huub A. M. Middelkoop Aachen Department of Neurology, Leiden University Medical Center (LUMC) Institute of Psychology, Health Medical and Neuropsychology Unit

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

    Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, The Netherlands

13. Geert Jan Biessels

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

14. Gisela Marie Terwindt Aachen Department of Neurology, Leiden University Medical Center (LUMC)

    Leiden University Medical Center

    Affiliation as printed

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

15. Matthias J.P. van Osch Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

16. Marianne A.A. van Walderveen Aachen Department of Radiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

17. Marieke J.H. Wermer Aachen Department of Neurology, Leiden University Medical Center (LUMC)

    University Medical Center Groningen · Leiden University Medical Center

    Affiliation as printed

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

    Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands