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The Cerebellum in Frontotemporal Dementia: a Meta-Analysis of Neuroimaging Studies

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Abstract

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant. We conducted an anatomical/activation likelihood estimation (ALE) meta-analysis in 53 neuroimaging studies (structural MRI: 42; positron emission tomography: 6; functional MRI: 4; single-photon emission computed tomography: 1) to identify the patterns of cerebellar changes and their relations to profiles of behavioural and cognitive deficits in FTD syndromes. Overall, widespread bilateral cerebellar changes were found in FTD and notably the patterns were subtype specific. In bvFTD, ALE peaks were identified in the bilateral Crus, left lobule VI, right lobules VIIb and VIIIb. In SD, focal cerebellar changes were located in the left Crus I and lobule VI. A separate ALE meta-analysis on PNFA studies was not performed due to the limited number of studies available. In addition, the ALE analysis indicated that bilateral Crus I and Crus II were associated with behavioural disruption and cognitive dysfunction. This ALE meta-analysis provides the quantification of the location and extent of cerebellar changes across the main FTD syndromes, which in turn provides evidence of cerebellar contributions to behavioural and cognitive changes in FTD. These results bring new insights into the mechanisms mediating FTD symptomatology.

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Acknowledgements

The authors are grateful for the kind assistance of the authors of the publications that were included in this study. We would like to thank Chengtao Liang for his help with ALE pipeline establishment. The authors wish to acknowledge the Sydney Informatics Hub at the University of Sydney for providing access to High Performance Computing (HPC). This work was supported in part by funding to Forefront, a collaborative research group specialised in the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council (NHMRC) of Australia program grant (APP1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders Memory Program (CE110001021). YC is supported by the State Scholarship Fund of China (No. 201608200010). FK is supported by an NHMRC-ARC Dementia Research Development Fellowship (APP1097026). RLR is supported by the Appenzeller Neuroscience Fellowship in Alzheimer’s Disease and the ARC Centre of Excellence in Cognition and its Disorders Memory Program (CE110001021). MI is supported by an ARC Future Fellowship (FT160100096). OP is supported by an NHMRC Senior Research Fellowship (APP1103258).

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Correspondence to Olivier Piguet.

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Chen, Y., Kumfor, F., Landin-Romero, R. et al. The Cerebellum in Frontotemporal Dementia: a Meta-Analysis of Neuroimaging Studies. Neuropsychol Rev 29, 450–464 (2019). https://doi.org/10.1007/s11065-019-09414-7

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  • DOI: https://doi.org/10.1007/s11065-019-09414-7

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