Reduced myelin contributes to cognitive impairment in patients with monogenic small vessel disease

Denecke, Jannis ; Dewenter, Anna ; Lee, Jongho; Franzmeier, Nicolai ; Valentim, Carolina; Kopczak, Anna ; Dichgans, Martin ; Pirpamer, Lukas; Gesierich, Benno; Duering, Marco und Ewers, Michael (2025): Reduced myelin contributes to cognitive impairment in patients with monogenic small vessel disease. In: Alzheimer's & Dementia, Bd. 21, Nr. 5, e70127

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: Myelin constitutes WM alterations distinct from diffusion changes and substantially contributes to explaining cognitive impairment in cSVD.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 666881
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198