Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease
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 biol...
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| Published in | CNS neuroscience & therapeutics Vol. 30; no. 9; pp. e70029 - n/a |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
John Wiley & Sons, Inc
01.09.2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1755-5930 1755-5949 1755-5949 |
| DOI | 10.1111/cns.70029 |
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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.
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. |
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| AbstractList | 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.AIMSThe 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.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.METHODSData 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.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.RESULTSSignificant 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.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.CONCLUSIONThe 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. 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. 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. 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. 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. 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. 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. |
| Author | He, Cancan Fan, Dandan Zhang, Zhijun Zang, Feifei Xie, Chunming Liu, Xinyi |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39302036$$D View this record in MEDLINE/PubMed |
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| Copyright | 2024 The Author(s). published by John Wiley & Sons Ltd. 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Keywords | cerebrospinal fluid biomarkers APOE Alzheimer's disease dynamic functional network connectivity lipid metabolism |
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| Notes | http://adni.loni.usc.edu As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database http://adni.loni.usc.edu/wp‐content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf . Data used in preparation of this article were generated by the Alzheimer's Disease Metabolomics Consortium (ADMC). As such, the investigators within the ADMC provided data but did not participate in analysis or writing of this report. A complete listing of ADMC investigators can be found at https://sites.duke.edu/adnimetab/team/ ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid... The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid... Aims The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid... |
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| SubjectTerms | 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 |
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| Title | Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease |
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