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Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales.

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MacDougall, Amy M 
Peakman, Georgia 
Bouzigues, Arabella 
Bocchetta, Martina 


OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). RESULTS: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). CONCLUSIONS: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.



Funder: Canadian Institutes of Health Research; doi:

Funder: Lemaire Family Foundation

Funder: Swedish Frontotemporal Dementia Initiative

Funder: Italian Ministry of Health

Funder: Weston Brain Institute; doi:

Funder: Mady Browaaeys Fund

Funder: Miriam Marks Brain Research UK

Funder: Bluefield Project


C9orf72, Frontotemporal dementia, Genetics, Motor, Progranulin, Tau, Humans, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, C9orf72 Protein, Tremor, Mutation, tau Proteins

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J Neurol

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Springer Science and Business Media LLC
Wellcome Trust (103838/Z/14/Z)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)