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Longitudinal resting-state functional connectivity and regional brain atrophy-based biomarkers of preclinical cognitive impairment in healthy old adults

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Abstract

Background

Intervention against age-related neurodegenerative diseases may be difficult once extensive structural and functional deteriorations have already occurred in the brain.

Aim

Investigating 6-year longitudinal changes and implications of regional brain atrophy and functional connectivity in the triple-network model as biomarkers of preclinical cognitive impairment in healthy aging.

Methods

We acquired longitudinal cognitive scores and magnetic resonance imaging (MRI) data from 74 healthy old adults. Resting-state functional MRI (rs-fMRI) analysis was conducted using FSL6.0.1 to examine functional connectivity changes and regional brain morphometries were quantified using FreeSurfer5.3. Finally, we cross-validated and compared two support vector machine (SVM) regression models to predict future 6-year cognition score from the baseline regional brain atrophy and resting-state functional connectivity (rs-FC) measures.

Results

After a 6-year follow-up, our results (P < 0.05-corrected) indicated significant connectivity reduction within all the three brain networks, significant differences in regional brain volumes and cortical thickness. We also observed significant improvement in episodic memory and significant decline in executive functions. Finally, comparing the two models, we observed that regional brain atrophy predictors were more efficient in approximating future 6-year cognitive scores (R = 0.756, P < 0.0001) than rs-FC predictors (R = 0.6, P < 0.0001).

Conclusion

This study used longitudinal data to keep subject variability low and to increase the validity of the results. We demonstrated significant changes in structural and functional MRI over 6 years. Our findings present a potential neuroimaging-based biomarker to detect cognitive impairment and prevent risks of neurodegenerative diseases in healthy old adults.

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Data availability

The magnetic resonance imaging (MRI) and neuropsychological tests data that support the findings of this study are available in [“OASIS-3”] with the identifier(s) [https://doi.org/10.1101/2019.12.13.19014902] [8]. OASIS-3 data are openly available to the scientific community at https://www.oasisbrains.org. Prior to accessing the data, users are required to agree to the OASIS data use terms (DUT), which follow the creative commons attribution 4.0 license.

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Acknowledgements

Authors acknowledge the free access of OASIS-3 data, openly available to the scientific community at https://www.oasisbrains.org. The funds were provided to the Knight ADRC and KARI by NIH P50AG00561, P30NS09857781, P01AG026276, P01AG003991, R01AG043434, R01AG054567, UL1TR000448, and R01EB009352, and Florbetapir doses provided by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.

Funding

This work was supported by the National Natural Science Foundation of China (Grant number: 81701665), Chinese Academy of Sciences (block grants) and the World Academy of Sciences (block grants).

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Authors and Affiliations

  1. Hefei National Lab for Physical Sciences at the Microscale and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China

    Jean de Dieu Uwisengeyimana, Benedictor Alexander Nguchu, Yaming Wang, Du Zhang, Yanpeng Liu, Zhoufan Jiang, Xiaoxiao Wang & Bensheng Qiu

  2. Department of Electrical and Electronics Engineering, College of Science and Technology, University of Rwanda, Kigali, Rwanda

    Jean de Dieu Uwisengeyimana

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  1. Jean de Dieu Uwisengeyimana
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Contributions

All authors contributed significantly and agreed with the content of the manuscript. Details about author contributions are as follows: conceptualization, data acquisition, methodology, and formal analysis: JdDU. Quality control (QC), and writing—review & editing: BAN. Quality control (QC), validation, and writing—review & editing: YW. Quality control (QC), and writing—review & editing: DZ. Quality control (QC), and writing—review & editing: YL. Quality control (QC), and writing—review & editing: ZJ. Supervision, resources, project administration, and funding acquisition: XW. Supervision, resources, project administration, and funding acquisition: BQ.

Corresponding authors

Correspondence to Xiaoxiao Wang or Bensheng Qiu.

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The authors state that all applicable institutional and/or national protocols for the human research project were followed and that they conform to the provisions of the Declaration of Helsinki.

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All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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de Dieu Uwisengeyimana, J., Nguchu, B.A., Wang, Y. et al. Longitudinal resting-state functional connectivity and regional brain atrophy-based biomarkers of preclinical cognitive impairment in healthy old adults. Aging Clin Exp Res 34, 1303–1313 (2022). https://doi.org/10.1007/s40520-021-02067-8

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