Purpose

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.

Methods

A total of 123 participants (31 healthy controls and 92 LBD patients) who underwent ¹⁸F-FDG PET scans were retrospectively enrolled. ¹⁸F-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.

Results

This ¹⁸F-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).

Conclusions

Our findings based on ¹⁸F-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.

中文翻译：

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代谢PET成像路易体痴呆的时空动态演化

 目的

路易体痴呆（LBD）是一种异质性高、发病机制复杂的神经退行性疾病。我们的研究旨在利用疾病进展模型来揭示LBD体内时空动态演化，并探索不同演化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。

 方法

共有 123 名参与者（31 名健康对照者和 92 名 LBD 患者）接受了^{18 次}F-FDG PET 扫描。建立基于¹⁸ F-FDG PET 的亚型和阶段推断 (SuStaIn) 模型来说明时空进化模式并对相关亚型进行分类。然后亚型和分期进一步与LBD患者的临床特征、糖代谢和多巴胺能功能相关。

 结果

这种基于¹⁸ F-FDG PET 成像的方法说明了 LBD 中源自新皮质和基底神经节的两种不同的神经退行性进化模式，并将它们分别定义为亚型 1 和亚型 2。亚型之间存在明显差异。与亚型1相比，亚型2男性患者比例较高（ P = 0.045），并出现幻视（ P = 0.033）和认知波动（ P = 0.033）等阳性症状。 2 亚型的认知障碍、代谢异常、多巴胺能功能障碍和进展均更为严重（均P < 0.05）。此外，还观察到 SuStaIn 亚型与两种临床表型（帕金森病痴呆和路易体痴呆）之间存在很强的相关性（ P = 0.005）。

 结论

我们基于¹⁸ F-FDG PET 和数据驱动模型的研究结果说明了 LBD 的时空动态演化，并对具有不同演化模式、体内临床和成像特征的新亚型进行了分类。进化相关的亚型与 LBD 临床表型相关，这支持了 LBD 谱系中存在不同实体的观点。