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Story of the ALS-FTD continuum retold: rather two distinct entities
  1. Dorothée E Lulé,
  2. Helena E A Aho-Özhan,
  3. Cynthia Vázquez,
  4. Ulrike Weiland,
  5. Jochen H Weishaupt,
  6. Markus Otto,
  7. Sarah Anderl-Straub,
  8. Elisa Semler,
  9. Ingo Uttner,
  10. Albert C Ludolph
  1. Department of Neurology, University of Ulm, Ulm, Germany
  1. Correspondence to Professor Dorothée E Lulé, Department of Neurology, Ulm University Hospital, Ulm D-89081, Germany; dorothee.lule{at}


Objective To determine the evolution and profile of cognitive and behavioural deficits in amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) to disentangle the development of FTD in ALS and vice versa.

Methods In a prospective design, cognitive and behavioural profiles of 762 patients with motor predominant ALS (flail arm/leg syndrome, primary lateral sclerosis, pseudobulbar palsy, ALS) and behavioural predominant FTD (bvFTD, ALS-FTD) were determined and caregivers of patients with ALS were asked on the evolution of behavioural symptoms. Data were compared with 49 healthy controls. Cognition was measured with the Edinburgh Cognitive and Behavioral ALS Screen.

Results Evolution and features of cognitive profile of patients with motor predominant ALS were distinctly different from patients with behavioural FTD with regard to number and degree of affected cognitive domains. Also, in ALS mostly minus symptoms evolved after physical symptom onset whereas in ALS-FTD plus and minus symptoms were reported with an onset before physical degradation.

Conclusion Evolution of cognitive and behavioural profile in patients with motor predominant ALS is distinctly different from those psychocognitive findings in patients with behavioural variant dementia. This may support the hypothesis that (possibly genetic) triggers decide in the preclinical phase on either motor or psychocognitive phenotypes.

  • cognitive neuropsychology
  • motor neuron disease
  • neuropsychology
  • frontotemporal dementia

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  • Contributors DEL designed the study, analysed the data and wrote the manuscript. IU assisted in interpretation of the data and revised the manuscript for intellectual content. HEAAO, CV, UW, JHW, MO, SAS, ES and ACL edited the manuscript for intellectual content.

  • Funding This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) Project (‘NEEDSinALS’ 01ED1405 and PreFrontALS 01ED1512). The project is supported through the following organisations under the aegis of JPND—, for example, Germany, Bundesministerium für Bildung und Forschung (BMBF, FKZ), Sweden, Vetenskaprådet Sverige, Poland, Narodowe Centrum Badań i Rozwoju (NCBR). This work was additionally funded by the Deutsche Forschungsgemeinschaft (DFG, LU 336/13-2), the Bundesministerium für Bildung und Forschung (FTLDc O1GI1007A, MND-Net 01GM1103A) and the foundation of the state Baden-Württemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009) and Thierry Latran Foundation.

  • Disclaimer The funding sources played no role in the preparation of this manuscript.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the Ethics Committee of the University of Ulm (19/12).

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

  • Data statement Data sharing requests are made in writing through DEL ( and require a formal data sharing agreement. Data sharing agreements must include details on how the data will be stored, who will have access to the data and intended use of the data, and agreements as to the allocation of intellectual property.