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

Autor:	Rasing I; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., Vlegels N; Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Schipper MR; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., Voigt S; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., Koemans EA; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., Kaushik K; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., van Dort R; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., van Harten TW; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., De Luca A; 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., van Etten ES; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., van Zwet EW; Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherland., van Buchem MA; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., Middelkoop HA; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.; Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, The Netherlands., Biessels GJ; Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Terwindt GM; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands., van Osch MJ; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., van Walderveen MA; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands., Wermer MJ; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2024 Jun 17, pp. 271678X241261771. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.1177/0271678X241261771
Abstrakt:	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. Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. Vlegels reports support by the Netherlands CardioVascular Research Initiative–the Dutch Heart Foundation (CVON 2018–28 & 2012–06). M.R. Schipper reports independent support from the TRACK D-CAA consortium, consisting of Alnylam, Biogen, the Dutch CAA foundation, Vereniging HCHWA-D, and researchers from Leiden, Boston, and Perth. A. De Luca reports independent support from Alzheimer Nederland (WE-03-2022-11) as well as from ZonMW. R. van Dort is funded by the TRACK D-CAA consortium, consisting of Biogen, Alnylam, the Dutch CAA foundation, Vereniging HCHWA-D, and researchers from Leiden, Boston, and Perth. G.M. Terwindt reports independent support from the Dutch Research Council (NWO), European Community, the Dutch Heart Foundation, the Dutch Brain Foundation, and the Dutch CAA foundation.M.J.P. van Osch reports support by a NWO-VICI grant (016.160.351) and a NWO-Human Measurement Models 2.0 grant (18969) as well as support from the Dutch Research Council (NWO), European Community, the Dutch Heart Foundation, and the Dutch Brain Foundation.M.J.H. Wermer reports independent support from de Nederlandse Organisatie voor Wetenschappelijk Onderzoek ZonMw (VIDI grant 91717337), the Netherlands Heart Foundation, and the Dutch CAA foundation. The others report no conflicts.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu