Microstructural white matter integrity in relation to vascular reactivity in Dutch-type hereditary cerebral amyloid angiopathy

Journal of Cerebral Blood Flow & Metabolism, vol. 43, pp. 2144–2155

Abstract

Cerebral Amyloid Angiopathy (CAA) is characterized by cerebrovascular amyloid-β accumulation leading to hallmark cortical MRI markers, such as vascular reactivity, but white matter is also affected. By studying the relationship in different disease stages of Dutch-type CAA (D-CAA), we tested the relation between vascular reactivity and microstructural white matter integrity loss. In a cross-sectional study in D-CAA, 3 T MRI was performed with Blood-Oxygen-Level-Dependent (BOLD) fMRI upon visual activation to assess vascular reactivity and diffusion tensor imaging to assess microstructural white matter integrity through Peak Width of Skeletonized Mean Diffusivity (PSMD). We assessed the relationship between BOLD parameters – amplitude, time-to-peak (TTP), and time-to-baseline (TTB) – and PSMD, with linear and quadratic regression modeling. In total, 25 participants were included (15/10 pre-symptomatic/symptomatic; mean age 36/59 y). A lowered BOLD amplitude (unstandardized β = 0.64, 95%CI [0.10, 1.18], p = 0.02, Adjusted R 2 = 0.48), was quadratically associated with increased PSMD levels. A delayed BOLD response, with prolonged TTP (β = 8.34 × 10 −6 , 95%CI [1.84 × 10 −6 , 1.48 × 10 −5 ], p = 0.02, Adj. R 2 = 0.25) and TTB (β = 6.57 × 10 −6 , 95%CI [1.92 × 10 −6 , 1.12 × 10 −5 ], p = 0.008, Adj. R 2 = 0.29), was linearly associated with increased PSMD. In D-CAA subjects, predominantly in the symptomatic stage, impaired cerebrovascular reactivity is related to microstructural white matter integrity loss. Future longitudinal studies are needed to investigate whether this relation is causal.

Authors 14

1. Naomi Vlegels

   University Medical Center Utrecht · Institut für Schlaganfall- und Demenzforschung · Ludwig-Maximilians-Universität München

   Affiliation as printed

   Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands

   Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany

2. 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

3. Ingeborg Rasing 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

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. 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

6. Alberto De Luca

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands

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

7. 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

8. 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

9. 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 Netherlands

10. 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

11. Geert Jan Biessels

    University Medical Center Utrecht

    Affiliation as printed

    Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands

12. 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

13. 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

14. 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