Abstract
In preclinical Alzheimer’s disease, neuro-functional changes due to amyloid-β (Aβ) deposition are not synchronized in different brain lobes and subcortical nuclei. This study aimed to explore the correlation between brain Aβ burden, connectivity changes in an ultra-large structural scale, and cognitive function in mild cognitive impairment. Participants with mild cognitive impairment were recruited and underwent florbetapir (F18-AV45) PET, resting-state functional MRI, and multidomain neuropsychological tests. AV-45 standardized uptake value ratio (SUVR) and functional connectivity of all participants were calculated. Of the total 144 participants, 72 were put in the low Aβ burden group and 72 in the high Aβ burden group. In the low Aβ burden group, all connectivities between lobes and nuclei had no correlation with SUVR. In the high Aβ burden group, SUVR showed negative correlations with the Subcortical-Occipital connectivity (r=-0.36, P = 0.02) and Subcortical-Parietal connectivity (r=-0.26, P = 0.026). Meanwhile, in the high Aβ burden group, SUVR showed positive correlations with the Temporal-Prefrontal connectivity (r = 0.27, P = 0.023), Temporal-Occipital connectivity (r = 0.24, P = 0.038), and Temporal-Parietal connectivity (r = 0.32, P = 0.006). Subcortical to Occipital and Parietal connectivities had positive correlations with general cognition, language, memory, and executive function. Temporal to Prefrontal, Occipital, and Parietal connectivities had negative correlations with memory function, executive function, and visuospatial function, and a positive correlation with language function. In conclusion, Individuals with mild cognitive impairment with high Aβ burden have Aβ-related bidirectional functional connectivity changes between lobes and subcortical nuclei that are associated with cognitive decline in multiple domains. These connectivity changes reflect neurological impairment and failed compensation.
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Study data are available on request to the authors.
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Acknowledgements
We would like to thank Jie-Hua Zhu, Yi-Fan Wang, Xian-Qing Xie, and Yun Yang for their help with neuropsychological tests.
Funding
This work was supported by the National Natural Science Foundation of China (82171198); Shanghai Municipal Science Technology Major Project (2018SHZDZX01); Guangdong Provincial Key S&T Program (2018B030336001); Innovation and Technology Commission of Hong Kong Project (MRP 042/18X); Shanghai Municipal Health Commission (202140042).
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Concept and design: Liang Cui, Zhen Zhang, Qi-Hao Guo. Drafting of the manuscript: Liang Cui. Critical revision of the manuscript for important intellectual content: Yi-Han Guo, Jie-Hui Jiang, Qi-Hao Guo. Statistical analysis: Liang Cui, Qi-Hao Guo. Obtained funding: Liang Cui, Qi-Hao Guo. Administrative, technical, or material support: Zhen Zhang, Yan-Lu Huang, Yi-Hui Guan, Chun-Yi Zac Lo, Fang Xie, Jie-Hui Jiang. Supervision: Jie-Hui Jiang, Qi-Hao Guo. All authors reviewed the manuscript.
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Cui, L., Zhang, Z., Huang, YL. et al. Brain amyloid-β deposition associated functional connectivity changes of ultra-large structural scale in mild cognitive impairment. Brain Imaging and Behavior 17, 494–506 (2023). https://doi.org/10.1007/s11682-023-00780-8
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DOI: https://doi.org/10.1007/s11682-023-00780-8