Journal Article

DZNE-2025-00589

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reduced myelin contributes to cognitive impairment in patients with monogenic small vessel disease.

Denecke, J. ; Dewenter, A. ; Lee, J. ; Franzmeier, N. ; Valentim, C. ; Kopczak, A. ; Dichgans, M.DZNE* ; Pirpamer, L. ; Gesierich, B.Extern* ; Duering, M. ; Ewers, M. (Last author)DZNE*

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.70127

Abstract: Myelin is pivotal for signal transfer and thus cognition. Cerebral small vessel disease (cSVD) is primarily associated with white matter (WM) lesions and diffusion changes; however, myelin alterations and related cognitive impairments in cSVD remain unclear.We included 64 patients with familial cSVD (i.e., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]) and 20 cognitively unimpaired individuals. χ separation applied to susceptibility weighted imaging was used to assess myelin and iron within WM hyperintensities, normal appearing WM, and two strategic fiber tracts. Diffusion-based mean diffusivity and free water were analyzed for comparisons. Cognitive impairment was assessed by the Trail Making Test.CADASIL patients showed reduced myelin within WM hyperintensities and its penumbra in the normal appearing WM. Myelin was moderately correlated with diffusion and iron changes and associated with slower processing speed controlled for diffusion and iron alterations.Myelin constitutes WM alterations distinct from diffusion changes and substantially contributes to explaining cognitive impairment in cSVD.χ-negative magnetic resonance signal was reduced within white matter hyperintensities and normal appearing white matter in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting widespread myelin decreases due to cerebral small vessel disease (cSVD). χ-negative values were only moderately associated with diffusion tensor imaging derived indices including free water and mean diffusivity, suggesting that χ separation depicts distinct microstructural changes in cSVD. Alterations in χ-negative values made a unique contribution to explain processing speed impairment, even when controlled for diffusion and iron changes.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Cognitive Dysfunction: etiology (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Middle Aged (MeSH) ; Myelin Sheath: pathology (MeSH) ; Myelin Sheath: metabolism (MeSH) ; White Matter: pathology (MeSH) ; White Matter: diagnostic imaging (MeSH) ; Cerebral Small Vessel Diseases: complications (MeSH) ; Cerebral Small Vessel Diseases: diagnostic imaging (MeSH) ; CADASIL: complications (MeSH) ; CADASIL: diagnostic imaging (MeSH) ; CADASIL: pathology (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Aged (MeSH) ; Diffusion Tensor Imaging (MeSH) ; Neuropsychological Tests (MeSH) ; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ; chi separation ; diffusion magnetic resonance imaging ; susceptibility mapping ; white matter hyperintensities

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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