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Heterogeneity of behavioural and language deficits in FTD–MND

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Journal of Neurology Aims and scope Submit manuscript

Abstract

Objective

To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia–motor neuron disease (FTD–MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD–MND using a data-driven approach.

Methods

Patients with FTD–MND (n = 31), behavioural variant FTD (n = 119), non-fluent variant primary progressive aphasia (n = 47), semantic variant primary progressive aphasia (n = 42), and controls (n = 127) underwent comprehensive clinical, cognitive and behavioural assessments. Two-step cluster analysis examined patterns of behavioural and language impairment. Voxel-based morphometry and tract-based spatial statistics were used to investigate differences across the subgroups that emerged from cluster analysis.

Results

More than half of FTD–MND patients initially presented with variable combinations of deficits (e.g., mixed behaviour/cognitive, mixed behaviour/cognitive/motor deficits), with 74% of them meeting criteria for FTD–MND within 24 months with a median of 12 months. The frequency and severity of behavioural and language abnormalities in FTD–MND lie between that seen in the three FTD phenotypes. Cluster analysis identified three patterns of behavioural and language impairment in FTD–MND. The three FTD–MND subgroups demonstrated different profiles of white matter tract disruption, but did not differ in age at onset, disease duration or patterns of cortical atrophy.

Conclusions

While highly heterogeneous, in terms of behavioural and language deficits, and disease severity, the presentation of FTD–MND may be distinct to that of FTD. Distinct white matter degeneration patterns may underpin heterogeneous clinical profiles in FTD–MND. FTD presenting with mixed behavioural-language disturbances should be monitored closely for at least 12–24 months for the emergence of MND symptoms/signs.

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Data availability

Anonymized data not published within the article will be shared on reasonable request from a qualified investigator for replication purposes.

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Acknowledgements

We are grateful to the research participants and their families.

Funding

This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neuron disease, from the National Health and Medical Research Council of Australia (NHMRC) program Grant (#1037746) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (#CE110001021). In addition, JRB was supported by a NHMRC Early Career Fellowship (#1072451). MI is supported by an ARC Future Fellowship (FT160100096). OP is supported by a NHMRC Senior Research Fellowship (APP1103258).

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Authors and Affiliations

  1. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhe Long

  2. The University of Sydney, The Faculty of Medicine and Health, Sydney, NSW, Australia

    Zhe Long, John R. Hodges & James R. Burrell

  3. The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia

    Zhe Long, Muireann Irish, David Foxe, John R. Hodges & Olivier Piguet

  4. The University of Sydney, School of Psychology, Sydney, NSW, Australia

    Muireann Irish, David Foxe & Olivier Piguet

  5. The University of Sydney, Faculty of Health Sciences, Sydney, NSW, Australia

    James R. Burrell

  6. The University of Sydney, Concord Medical School, Sydney, NSW, Australia

    James R. Burrell

  7. ARC Centre of Excellence in Cognition and Its Disorders, Sydney, NSW, Australia

    Muireann Irish, John R. Hodges, Olivier Piguet & James R. Burrell

  8. Neurosciences 5West, Concord Repatriation General Hospital, Sydney, NSW, 2139, Australia

    James R. Burrell

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  1. Zhe Long
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  2. Muireann Irish
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Correspondence to James R. Burrell.

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The authors report no competing interests.

Ethical approval

The study was approved by the ethics committees of the University of New South Wales and South Eastern Sydney Local Health District. In accordance with the Declaration of Helsinki, written informed consent was obtained from all participants, or their carers.

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Long, Z., Irish, M., Foxe, D. et al. Heterogeneity of behavioural and language deficits in FTD–MND. J Neurol 268, 2876–2889 (2021). https://doi.org/10.1007/s00415-021-10451-7

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  • DOI: https://doi.org/10.1007/s00415-021-10451-7

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