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Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study

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Abstract

Postmortem studies on patients with Alzheimer’s disease (AD) have confirmed that the dorsal raphe nucleus (DRN) in the brainstem is the first brain structure affected in the earliest stage of AD. The present study examined the brainstem in the early stage of AD using magnetic resonance (MR) imaging. T1-weighted MR images of the brains of 81 subjects were obtained from the publicly available Open Access Series of Imaging Studies (OASIS) database, including 27 normal control (NC) subjects, 27 patients with very mild AD (AD-VM) and 27 patients with mild AD (AD-M). The brainstem was interactively segmented from the MR images using ITK-SNAP. The present voxel-based morphometry (VBM) study was designed to investigate the brainstem differences between the AD-VM/AD-M groups and the NC group. The results showed bilateral loss in the pons and the left part of the midbrain in the AD-M group compared to the NC group. The AD-M group showed greater loss in the left midbrain than the AD-VM group (PFWEcorrected < 0.05). The results revealed that brainstem atrophy occurs in the early stages of AD (Clinical Dementia Rating = 0.5 and 1.0). Most of these findings were also investigated in a multicenter dataset. This is the first VBM study that provides evidence of brainstem alterations in the early stage of AD.

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Notes

  1. https://www.fil.ion.ucl.ac.uk/spm/

  2. https://surfer.nmr.mgh.harvard.edu/

  3. www.itksnap.org

  4. http://www.oasis-brains.org

  5. http://adni.loni.usc.edu

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Funding

This study was founded by the Science and Technology Cooperation Direction Project of Hainan Key Research and Development Plan (grant number ZDYD2019207) and National Natural Science Foundation of China (grant numbers 81171304, 81201150 and 81500924). It was also supported by Sanya Key Laboratory Construction (grant number L1232) and Natural Science Foundation of Hainan Province of China (grant number 20158306). The OASIS dataset used in this work was funded by grants (P50 AG05681, P01 AG03991, R01 AG021910, P50 MH071616, U24 RR021382, R01 MH56584). Data used in preparation of this article were obtained from the ADNI database (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 this report. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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  1. Xiaoxi Ji, Hui Wang and Minwei Zhu contributed equally to this work.

Authors and Affiliations

  1. School of Life Science and Technology, Harbin Institute of Technology, Building 2E-417, 2 Yikuang Street, Nangang District, Harbin, Heilongjiang Province, China

    Xiaoxi Ji, Wenpeng Gao & Yili Fu

  2. Guangzhou Medical University, Guangzhou, China

    Xiaoxi Ji, Yingjie He & Hong Zhang

  3. Department of Neurosurgery, Third People’s Hospital of Hainan Province, 146 Jiefang Road, Sanya, Hainan Province, China

    Xiaoxi Ji, Hui Wang, Yingjie He, Hong Zhang & Xiaoguang Chen

  4. Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China

    Minwei Zhu

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for the Alzheimer’s Disease Neuroimaging Initiative

Contributions

Author contributions included conception and study design (Wenpeng Gao and Xiaoguang Chen), data collection or acquisition (Xiaoxi Ji, Hong Zhang and Yingjie He), statistical analysis (Xiaoxi Ji, Hui Wang and Minwei Zhu), interpretation of results (Xiaoxi Ji, Hui Wang, Minwei Zhu, Wenpeng Gao), drafting the manuscript work or revising it critically for important intellectual content (Xiaoxi Ji, Minwei Zhu, Wenpeng Gao, Xiaoguang Chen and Yili Fu) and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (All authors).

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Correspondence to Xiaoguang Chen or Wenpeng Gao.

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Ji, X., Wang, H., Zhu, M. et al. Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study. Brain Imaging and Behavior 15, 49–59 (2021). https://doi.org/10.1007/s11682-019-00231-3

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