Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
Eur J Nucl Med Mol Imaging. 2024 Dec;52(1):145-157. doi: 10.1007/s00259-024-06881-w. Epub 2024 Aug 19.
Lewy body dementia (LBD) is a neurodegenerative disease with high heterogeneity and complex pathogenesis. Our study aimed to use disease progression modeling to uncover spatial-temporal dynamic evolution of LBD in vivo, and to explore differential profiles of clinical features, glucose metabolism, and dopaminergic function among different evolution-related subtypes.
A total of 123 participants (31 healthy controls and 92 LBD patients) who underwent F-FDG PET scans were retrospectively enrolled. F-FDG PET-based Subtype and Stage Inference (SuStaIn) model was established to illustrate spatial-temporal evolutionary patterns and categorize relevant subtypes. Then subtypes and stages were further related to clinical features, glucose metabolism, and dopaminergic function of LBD patients.
This F-FDG PET imaging-based approach illustrated two distinct patterns of neurodegenerative evolution originating from the neocortex and basal ganglia in LBD and defined them as subtype 1 and subtype 2, respectively. There were obvious differences between subtypes. Compared with subtype 1, subtype 2 exhibited a greater proportion of male patients (P = 0.045) and positive symptoms such as visual hallucinations (P = 0.033) and fluctuating cognitions (P = 0.033). Cognitive impairment, metabolic abnormalities, dopaminergic dysfunction and progression were all more severe in subtype 2 (all P < 0.05). In addition, a strong association was observed between SuStaIn subtypes and two clinical phenotypes (Parkinson's disease dementia and dementia with Lewy bodies) (P = 0.005).
Our findings based on F-FDG PET and data-driven model illustrated spatial-temporal dynamic evolution of LBD and categorized novel subtypes with different evolutionary patterns, clinical and imaging features in vivo. The evolution-related subtypes are associated with LBD clinical phenotypes, which supports the perspective of existence of distinct entities in LBD spectrum.
路易体痴呆（LBD）是一种具有高度异质性和复杂发病机制的神经退行性疾病。本研究旨在使用疾病进展建模来揭示 LBD 体内的时空动态演变，并探讨不同演变相关亚型之间临床特征、葡萄糖代谢和多巴胺能功能的差异特征。
回顾性纳入了 123 名接受 F-FDG PET 扫描的参与者（31 名健康对照和 92 名 LBD 患者）。建立了基于 F-FDG PET 的亚型和阶段推断（SuStaIn）模型，以说明时空演变模式并对相关亚型进行分类。然后将亚型和阶段与 LBD 患者的临床特征、葡萄糖代谢和多巴胺能功能进一步相关联。
这种基于 F-FDG PET 成像的方法说明了 LBD 中源自皮质和基底节的两种不同的神经退行性演变模式，并分别将其定义为亚型 1 和亚型 2。亚型之间存在明显差异。与亚型 1 相比，亚型 2 中男性患者的比例更高（P=0.045），且阳性症状如视幻觉（P=0.033）和波动认知（P=0.033）更为常见。亚型 2 的认知障碍、代谢异常、多巴胺能功能障碍和进展更为严重（均 P<0.05）。此外，SuStaIn 亚型与两种临床表型（帕金森病痴呆和路易体痴呆）之间存在很强的关联（P=0.005）。
本研究基于 F-FDG PET 和数据驱动模型，说明了 LBD 的时空动态演变，并对体内具有不同演变模式、临床和影像学特征的新型亚型进行了分类。与演变相关的亚型与 LBD 临床表型相关，这支持了 LBD 谱中存在不同实体的观点。
