Denecke Jannis, Dewenter Anna, Lee Jongho, Franzmeier Nicolai, Valentim Carolina, Kopczak Anna, Dichgans Martin, Pirpamer Lukas, Gesierich Benno, Duering Marco, Ewers Michael
Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Munich, Germany.
Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering, Seoul, Republic of Korea.
Alzheimers Dement. 2025 May;21(5):e70127. doi: 10.1002/alz.70127.
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.
髓磷脂对信号传递乃至认知起着关键作用。脑小血管疾病（cSVD）主要与白质（WM）病变及扩散变化相关；然而，cSVD中的髓磷脂改变及相关认知障碍仍不明确。
我们纳入了64例家族性cSVD患者（即伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病[CADASIL]）以及20名认知功能未受损的个体。应用于磁敏感加权成像的χ分离法用于评估WM高信号、正常WM以及两条关键纤维束内的髓磷脂和铁。分析基于扩散的平均扩散率和自由水以进行比较。通过连线测验评估认知障碍。
CADASIL患者在WM高信号及其在正常WM中的半暗带内髓磷脂减少。髓磷脂与扩散和铁的变化呈中度相关，并与在控制了扩散和铁改变后的较慢处理速度相关。
髓磷脂构成了与扩散变化不同的WM改变，并在很大程度上有助于解释cSVD中的认知障碍。
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病患者的白质高信号和正常白质内的χ阴性磁共振信号降低，提示脑小血管疾病（cSVD）导致广泛的髓磷脂减少。χ阴性值仅与包括自由水和平均扩散率在内的扩散张量成像衍生指标中度相关，表明χ分离描绘了cSVD中独特的微观结构变化。即使在控制了扩散和铁的变化后，χ阴性值的改变对解释处理速度损害也有独特贡献。
