Hannaway Naomi, Zarkali Angeliki, Bhome Rohan, Dobreva Ivelina, Thomas George E C, Veleva Elena, Belio Irene Gorostiaga, Tucker Katie, Heslegrave Amanda, Zetterberg Henrik, Weil Rimona S
Dementia Research Centre, UCL Institute of Neurology, London, UK.
UCL Hawkes Institute, Department of Computer Science, London, UK.
Alzheimers Dement. 2025 May;21(5):e70274. doi: 10.1002/alz.70274.
Despite ongoing debate about whether Parkinson's disease (PD) dementia (PDD) and dementia with Lewy bodies (DLB) are separable diseases or a single Lewy body dementia (LBD) spectrum, there are limited investigations of differences between these conditions.
We used fixel-based diffusion magnetic resonance imaging and plasma measures to examine white matter integrity and burden of amyloid pathology (using phosphorylated tau-217 [p-tau217]) in 47 patients with DLB, 21 with PDD, 29 with PD, and 23 age-matched controls.
We show reduced fiber cross-section in LBD versus PD, and increased concentrations of plasma neurofilament light chain and p-tau217; with p-tau217 and fiber cross-section associated with cognition. Fiber density was reduced in PDD versus DLB, but neither plasma measures nor fiber cross-section differed between LBD subtypes.
Our findings suggest that the presence of dementia in LBD is associated with poorer white matter macrostructure and may relate to pathological protein accumulation. Conversely, differences between DLB and PDD may be driven by other factors.
Plasma neurofilament light and phosphorylated tau-217 were increased in Lewy body dementia (LBD) relative to Parkinson's disease (PD) and controls. Magnetic resonance imaging (MRI) white matter macrostructure (fiber cross-section) was reduced in LBD relative to PD. In contrast, MRI white matter microstructure (fiber density) was reduced in PD dementia compared to dementia with Lewy bodies. Differences between dementia with Lewy bodies and PD dementia were distinct compared with those between LBD and Parkinson's with normal cognition. Our findings suggest that dementia with Lewy bodies and Parkinson's dementia differ in underlying processes distinct from those driving dementia.
尽管关于帕金森病（PD）痴呆（PDD）和路易体痴呆（DLB）是可分离的疾病还是单一的路易体痴呆（LBD）谱系仍在持续争论，但对这些病症之间差异的研究有限。
我们使用基于固定点的扩散磁共振成像和血浆检测，来检查47例DLB患者、21例PDD患者、29例PD患者以及23例年龄匹配的对照者的白质完整性和淀粉样蛋白病理负担（使用磷酸化tau-217 [p-tau217]）。
我们发现，与PD相比，LBD患者的纤维横截面积减小，血浆神经丝轻链和p-tau217浓度升高；p-tau217和纤维横截面积与认知相关。与DLB相比，PDD患者的纤维密度降低，但LBD亚型之间的血浆检测结果和纤维横截面积均无差异。
我们的研究结果表明，LBD中痴呆的存在与较差的白质宏观结构相关，可能与病理性蛋白质积累有关。相反，DLB和PDD之间的差异可能由其他因素驱动。
与帕金森病（PD）和对照组相比，路易体痴呆（LBD）患者的血浆神经丝轻链和磷酸化tau-217升高。与PD相比，磁共振成像（MRI）显示LBD患者的白质宏观结构（纤维横截面积）减小。相比之下，与路易体痴呆相比，帕金森病痴呆患者的MRI白质微观结构（纤维密度）减小。与认知正常的LBD和帕金森病患者之间的差异相比，路易体痴呆和帕金森病痴呆之间的差异更为明显。我们的研究结果表明，路易体痴呆和帕金森病痴呆在潜在机制上存在差异，不同于导致痴呆的机制。
