The frontotemporal syndrome of ALS Profile, screening and progression

The frontotemporal syndrome of amyotrophic lateral sclerosis (ALS) consists of cognitive and behavioural impairment and occurs in 30-50% of ALS patients. Approximately 10% of patients fulfils criteria for behavioural variant frontotemporal dementia (bvFTD), which has a negative influence on quality of life and adherence to life-prolonging therapies. It is therefore important to assess the presence of a frontotemporal syndrome. In the first part of this thesis we determined the cognitive profiles of ALS and bvFTD by means of a meta-analysis, and showed that they show great similarities, with impairment in social cognition, executive functions and verbal memory. We systematically reviewed the behavioural profile of ALS and found that perseveration, apathy and disinhibition occur most frequently. In the second part of this thesis we developed screening instruments for cognitive and behavioural impairment. We developed and validated a behavioural questionnaire, the ALS-FTD-Questionnaire, which is currently being used worldwide in ALS clinics and research projects. We also developed a cognitive screening instrument for ALS patients, of which the clinimetric properties were less than expected. In the third part of this thesis, we investigated the course of cognitive and behavioural impairment in early ALS patients (disease duration < 12 months). Patients underwent a neuropsychological and behavioural evaluation at baseline and after six months. Thirty percent had new impairment or progression of impairment at follow-up. We also investigated survival in a large cohort of ALS patients and found a negative influence of the frontotemporal syndrome.