The frontotemporal syndrome of ALS is associated with poor survival

Rosanne Govaarts*, Emma Beeldman, Mike J. Kampelmacher, Marie-Jose van Tol, Leonard H. van den Berg, Anneke J. van der Kooi, Peter J. Wijkstra, Marianne Zijnen-Suyker, Nicolle A. M. Cobben, Ben A. Schmand, Rob J. de Haan, Marianne de Visser, Joost Raaphorst

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as > 22 points on the ALS-Frontotemporal-Dementia-Questionnaire or aeyen3 points on aeyen2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on aeyen2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53-5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44-3.65, p <0.001) in a multivariate model. Patients with an FS had a shorter survival after NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV.
Original languageEnglish
Pages (from-to)2476-2483
Number of pages8
JournalJournal of Neurology
Issue number12
Publication statusPublished - Dec 2016


  • Amyotrophic lateral sclerosis
  • Frontotemporal syndrome
  • Cognitive impairment
  • Behavioral changes
  • Survival
  • Non-invasive ventilation

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