Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-09-20 DOI:10.1111/cns.70029

Feifei Zang, Xinyi Liu, Dandan Fan, Cancan He, Zhijun Zhang, Chunming Xie, for the Alzheimer's Disease Neuroimaging Initiative, for the Alzheimer's Disease Metabolomics Consortium

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Abstract

Aims

The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid metabolism-related factors across the Alzheimer's disease (AD) spectrum populations.

Methods

Data from 242 AD spectrum subjects, including biological, neuroimaging, and general cognition, were obtained from the Alzheimer's Disease Neuroimaging Initiative for this cross-sectional study. The study utilized a sliding-window approach to assess whole-brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid-related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance.

Results

Significant group difference concerning were observed in relation to APOE-ε4 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference for spending more time in state-I, whereas AD patients tended remain in state-II for longer periods. Group difference in dFNC was primarily found between AD and non-AD participants within each state. The dFNC of state-I yielded strong power to distinguish AD from other groups compared with state-II. APOE-ε4⁺, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state-I, whereas differential connections of state-II mediated the relationships between APOE-ε4 genotype and CSF biomarkers, and cognitive indicators.

Conclusion

The dysfunction of dFNC temporal–spatial patterns and increased cognition in individuals with APOE-ε4, high polygenic score, and higher serum lipid levels shed light on the lipid-related mechanisms of dynamic network reorganization in AD.

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阿尔茨海默病的动态功能网络连接及其与脂质代谢的关系

研究目的研究阿尔茨海默病（AD）谱系人群中动态功能网络连通性（dFNC）的变化轨迹特征及其与脂质代谢相关因素的相关性。方法本横断面研究从阿尔茨海默病神经影像学倡议中获得了 242 名阿尔茨海默病谱系受试者的数据，包括生物学、神经影像学和一般认知。研究采用滑动窗口法评估全脑 dFNC，调查群体差异以及与生物和认知因素的关联。支持向量机将异常的dFNC用于AD谱系人群的分类。对血脂相关指标、dFNC、脑脊液（CSF）生物标志物和认知能力之间的关系进行了中介分析。结果在APOE-ε4状态、脑脊液生物标志物和认知评分之间观察到了显著的组间差异。研究发现了两种反复出现的连接状态：状态-1 的特点是连接频繁但连接较弱，状态-II 的特点是连接较少但连接较强。AD前期受试者表现出更多时间处于状态-I，而AD患者则倾向于更长时间处于状态-II。在每种状态下，注意力缺失症患者和非注意力缺失症患者的 dFNC 主要存在群体差异。与状态-II相比，状态-I的dFNC具有很强的区分AD和其他群体的能力。APOE-ε4+、高多基因评分和高血脂组与联想皮层系统和感觉皮层系统之间的网络破坏密切相关，而联想皮层系统和感觉皮层系统之间的网络破坏是认知功能提升的特征，这可能暗示了状态-Ⅰ中dFNC的代偿机制，而状态-Ⅱ的不同连接则介导了APOE-ε4基因型和CSF生物标志物以及认知指标之间的关系。结论 APOE-ε4、高多基因评分和较高血清脂质水平个体的dFNC时空模式功能障碍和认知能力增强，揭示了AD动态网络重组的脂质相关机制。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.