The frontotemporal syndrome of ALS Clinical progression & changing brain networks

The frontotemporal syndrome of amyotrophic lateral sclerosis (ALS) consists of cognitive and behavioural impairment. Approximately 50% of the ALS patients have mild cognitive and/or behavioural impairment and around 10% of the ALS patients have a concomitant diagnosis of the behavioural variant of frontotemporal dementia (bvFTD). The combination of ALS and bvFTD negatively influences survival and interferes with the initiation and compliance of life-prolonging therapies.
In the first part of the thesis the course of cognitive and behavioural impairment and the impact on survival of ALS patients were examined. We showed that 30% of early symptomatic ALS patients (disease duration <12 months) had a progressive course of cognitive and behavioural impairment over a 6-month period. We also investigated survival in a large cohort of ALS patients and found evidence for a reduced survival in ALS patients with cognitive and/or behavioural impairment, which persisted after initiation of non-invasive ventilation.
In the second part of this thesis we described the electrophysiological processes of ALS patients compared to healthy controls and bvFTD patients. For this study, we used magnetoencephalography (MEG), a method to measure brain signals in both cortical and subcortical regions. We showed an overlap in resting-state functional connectivity changes in cortical and subcortical brain regions between ALS and bvFTD patients compared to healthy controls. Additionally, we demonstrated that brain networks of ALS patients with cognitive and/or behavioural impairment move along the ALS-bvFTD spectrum over time and become closer to bvFTD like topology.