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Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis
  1. Jennifer A Saxon1,2,
  2. Jennifer C Thompson1,2,
  3. Jennifer M Harris1,2,
  4. Anna M Richardson1,2,
  5. Tobias Langheinrich1,2,
  6. Sara Rollinson2,
  7. Stuart Pickering-Brown2,
  8. Amina Chaouch3,
  9. John Ealing2,3,
  10. Hisham Hamdalla2,3,
  11. Carolyn A Young4,5,
  12. Dan Blackburn6,
  13. Tahir Majeed7,
  14. Claire Gall7,
  15. Matthew Jones1,2,
  16. Julie S Snowden1,2
  1. 1Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK
  2. 2Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester, UK
  3. 3Motor Neurone Disease Care Centre, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK
  4. 4Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UK
  5. 5Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
  6. 6Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, Sheffield, UK
  7. 7Neurology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
  1. Correspondence to Professor Julie S Snowden, Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK; julie.snowden{at}


Objective The precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone.

Methods Patients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes.

Results 23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests’ sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks.

Conclusions Differences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS.

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  • Contributors JAS: study design, data acquisition and analysis, drafting of manuscript. JCT: conception and design, data acquisition and analysis, interpretation, critical review and revision of manuscript. JMH: acquisition of control data, critical review and approval of manuscript. AMR, TL, AC, JE, HH, CAY, DB, TM, CG: screening and recruitment of participants, review and approval of manuscript. SR, SP-B: genetic analysis, review and approval of manuscript. MJ, JSS: conception and design, data analysis, interpretation, critical review and revision of manuscript.

  • Funding JAS was funded by the Motor Neurone Disease Association through a PhD Studentship award, grant reference Snowden/Oct13/872-792.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All participants provided informed written consent to take part in the study, which was approved by the National Research Ethics Committee North West (Greater Manchester South), REC reference 14/NW/1185).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Requests for data sharing should be made in writing to the corresponding author. Requests will be considered individually at departmental research/clinical governance meetings.

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