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Brain structural and perfusion changes in amyotrophic lateral sclerosis-frontotemporal dementia patients with cognitive and motor onset: a preliminary study

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Abstract

Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) is rare but exhibits worse prognosis than either ALS or FTD alone. However, cognitive onset ALS-FTD (ALS-FTD-C) confers significantly better patient survival than does motor onset ALS-FTD (ALS-FTD-M), underscoring a meager understanding of pathological group differences. This study aimed to assess disparities in cortical atrophy and perfusion shown by patients with the above disease variants. A total of 38 participants (ALS-FTD-C, 8; ALS-FTD-M, 6; simultaneous-onset ALS-FTD [ALS-FTD-S], 4; healthy controls [HC], 20) qualified for the study and underwent magnetic resonance imaging scan. Three-dimensional T1-weighted structural brain imaging and 3D-pseudocontinuous arterial spin-labeled imaging were routinely collected. Gray matter volume (GMV) and cerebral blood flow (CBF) in ALS-FTD-C and ALS-FTD-M were compared through voxel-based analysis. Correlations between imaging parameters and clinical data were also assessed. Compared with HC, ALS-FTD had significant GMV reduction mainly in bilateral limbic system. GMV reduction in ALS-FTD-C was similar in pattern but less widespread, whereas ALS-FTD-M lacked any significant GMV reduction. In CBF analyses, ALS-FTD displayed hypoperfusion in bilateral motor cortex, frontotemporal lobe, and left basal ganglia. Hypoperfusion involved bilateral temporal lobe, prefrontal cortex, and putamen in ALS-FTD-C but was limited to left parahippocampal gyrus in ALS-FTD-M. Correlations between clinical data and GMV/CBF changes in specific regions were also identified in ALS-FTD. Group-specific patterns of cortical atrophy and perfusion were evident in ALS-FTD-C and ALS-FTD-M. ALS-FTD-C showed pronounced cortical atrophy and hypoperfusion, which were otherwise minimal in ALS-FTD-M. Above findings preliminarily revealed the pathological group differences that may help in classifying patients with ALS-FTD.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the ALS-FTD patients and healthy controls for participating in this study.

Funding

This study was supported by the National Natural Science Foundation of China (Grant number: 81801277) and the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant number: XDB39000000).

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  1. Yanying Wang and Dongchao Shen contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China

    Yanying Wang, Dongchao Shen, Xiaohan Sun, Xunzhe Yang, Jing Gao, Mingsheng Liu & Liying Cui

  2. Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

    Bo Hou & Feng Feng

  3. Neuroscience Centre, Chinese Academy of Medical Sciences, Beijing, China

    Liying Cui

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  1. Yanying Wang
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Contributions

YW and DS: study concept and design, data acquisition, statistical analysis, data interpretation, drafting of the manuscript. BH: data acquisition, statistical analysis, critical revision of the manuscript. XS, XY, JG, and ML: data acquisition, study supervision, critical revision of the manuscript. FF: study concept and design, data interpretation, critical revision of the manuscript. LC: study concept and design, data acquisition, data interpretation, study supervision, critical revision of the manuscript.

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Correspondence to Liying Cui.

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This study was approved by the Research Ethics Committee of Peking Union Medical College Hospital (No. JS-2509).

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Wang, Y., Shen, D., Hou, B. et al. Brain structural and perfusion changes in amyotrophic lateral sclerosis-frontotemporal dementia patients with cognitive and motor onset: a preliminary study. Brain Imaging and Behavior 16, 2164–2174 (2022). https://doi.org/10.1007/s11682-022-00686-x

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