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

• Published in: CNS neuroscience & therapeutics Vol. 30; no. 9; pp. e70029 - n/a
• Main Authors: Zang, Feifei, Liu, Xinyi, Fan, Dandan, He, Cancan, Zhang, Zhijun, Xie, Chunming
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2024
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - metabolism; Alzheimer's disease; APOE; Apolipoprotein E; Apolipoprotein E4 - genetics; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Brain - diagnostic imaging; Brain - metabolism; Brain research; Cerebrospinal fluid; cerebrospinal fluid biomarkers; Cholesterol; Cognitive ability; Cross-Sectional Studies; Disease; dynamic functional network connectivity; Female; Genotypes; Health risk assessment; Humans; Lipid metabolism; Lipid Metabolism - physiology; Lipids; Lipoproteins; Low density lipoprotein receptors; Magnetic Resonance Imaging; Male; Memory; Metabolism; Middle Aged; Nerve Net - diagnostic imaging; Nerve Net - metabolism; Neural networks; Neurodegenerative diseases; Neuroimaging; Neurosciences; Pathology; Polygenic inheritance; Proteins; Somatosensory cortex; Temporal lobe; Variance analysis; cerebrospinal fluid biomarkers; APOE; Alzheimer's disease; dynamic functional network connectivity; lipid metabolism
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.70029

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. Alzheimer's disease is recognized to be associated with dysregulation of lipid metabolism and abnormal tempo‐spatial patterns of dynamic functional network connectivity. The dynamic connectivity represented a better power in differentiating Alzheimer's disease patients from non‐Alzheimer's disease subjects than static connectivity. Differential connectivity of strong‐connected state between APOE‐ε4 carriers and non‐carriers mediated the relationship between Apolipoprotein E‐ε4 genotype and cerebrospinal fluid and cognitive indicators.