Zarkali Angeliki, Thomas George, Paterson Ross, Hannaway Naomi, Dobreva Ivelina, Heslegrave Amanda J, Veleva Elena, Zetterberg Henrik, Weil Rimona S
Dementia Research Centre, Institute of Neurology, University College London, London, UK.
National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Mov Disord. 2025 Aug 7. doi: 10.1002/mds.30325.
Impaired glymphatic clearance may contribute to pathological accumulations in Parkinson's (PD), but how it interacts with other processes causing dementia remains unclear. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as an indirect proxy for glymphatic clearance.
To clarify DTI-ALPS' relationship with cognition in PD, and its relationship with established imaging markers.
We assessed DTI-ALPS in 98 PD patients (31 PD poor outcomes: dementia, mild cognitive impairment, frailty, or death within a 3-year follow-up; 67 PD good outcomes) and 28 controls. We assessed DTI-ALPS' relationship to cognition, white matter (fiber cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping [QSM]), and plasma markers [phosphorylated tau-181 (p-tau181 and neurofilament light (NfL)] cross-sectionally and longitudinally).
DTI-ALPS was lower in PD-poor outcomes compared with PD good outcomes and controls (P = 0.005) with further longitudinal reductions only in PD poor outcomes (group × time interaction: β = -0.013, P = 0.021). Lower DTI-ALPS was associated with lower fiber cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma p-tau181 (P = 0.642), NFL (P = 0.448), or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution.
PD patients who develop poor outcomes show lower DTI-ALPS, potentially reflecting impaired glymphatic clearance. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia, suggesting DTI-ALPS captures a distinct contribution to cognitive decline. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
类淋巴系统清除功能受损可能导致帕金森病（PD）出现病理性蓄积，但它如何与其他导致痴呆的过程相互作用尚不清楚。沿血管周围间隙的扩散张量图像分析（DTI-ALPS）已被提议作为类淋巴系统清除功能的间接替代指标。
阐明DTI-ALPS与PD患者认知功能的关系，以及它与已确立的影像学标志物的关系。
我们评估了98例PD患者（31例预后不良：痴呆、轻度认知障碍、虚弱或在3年随访期内死亡；67例预后良好）和28名对照者的DTI-ALPS。我们从横断面和纵向评估了DTI-ALPS与认知、白质（纤维横截面积）、皮质厚度、铁蓄积（定量磁化率成像[QSM]）以及血浆标志物[磷酸化tau-181（p-tau181）和神经丝轻链（NfL）]的关系。
与预后良好的PD患者和对照者相比，预后不良的PD患者DTI-ALPS较低（P = 0.005），且仅在预后不良的PD患者中出现进一步的纵向降低（组×时间交互作用：β = -0.013，P = 0.021）。较低的DTI-ALPS在基线和纵向与PD患者较低的纤维横截面积相关，但与PD认知相关的白质变化的空间分布不同。基线DTI-ALPS与血浆p-tau181（P = 0.642）、NFL（P = 0.448）或基线皮质厚度之间无相关性。较低的DTI-ALPS与左侧中央前回内皮质变薄加速以及脑铁分布变化相关。
预后不良的PD患者DTI-ALPS较低，可能反映类淋巴系统清除功能受损。DTI-ALPS与白质完整性和脑铁蓄积相关。然而，两者的空间分布均与PD痴呆不同，提示DTI-ALPS对认知功能下降有独特的影响。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
