A different cognitive and behavioral profile in ALS patients with or without C9orf72 expansion
Cristina Moglia1, Barbara Iazzolino1, Laura Peotta1, Jean Pierre Zucchetti1, Antonio Canosa1, francesca palumbo1, Umberto Manera1, Maura Brunetti1, Andrea Calvo1, Adriano Chio1
1Neuroscience Department, University of Turin

The aim of this study was to analyze whether ALS patients with C9orf72 expansion showed a different profile of cognitive and behavioral domains compared to patients without C9orf72 expansion (a) at the same level of motor impairment, classified according to King’s staging system, and (b) at the same degree of cognitive and behavioral deficit, classified according to the revised ALS-FTD Consensus Criteria.

Six to 10 percent of Amyotrophic lateral sclerosis (ALS) patients carry a pathological expansion of the C9orf72 gene. Patients carrying this mutation are more likely to present a cognitive and behavioral impairment. However, very few is known about the specific cognitive domains that are differentially involved in patients with (ALSC9+) or without (ALSC9-) C9orf72 expansion. 

We considered 741 ALS patients, consecutively seen at the Turin ALS center in the period 2010-2018, who underwent both cognitive/behavioral and genetic testing. Patients were diagnosed according to El Escorial revised criteria. Kings’ staging and genetic analysis at time of cognitive testing were collected for all patients. ALS patients underwent a neuropsychological battery selected according to the ALS-FTD Consensus Criteria. 


ALSC9+ patients were younger than ALSC9- at all levels of cognitive impairment. ALSC9+ patients had significantly lower scores in tests exploring executive functions and verbal memory. Considering the clinical perspective, ALSC9+ patients showed significantly lower scores compared to ALSC9- patients at King’s stage 1 and 3 in almost all the examined neuropsychological domains, while at King’s stage 2 ALSC9+ patients were more severely affected only in the verbal memory domain. Behavioral function was comparably impaired in the two cohorts. 

Our data suggest that ALSC9+ patients show a comparatively different neuropsychological pattern. This could imply in ALSC9+ patients a ‘cognitive’ presymptomatic/subclinical condition characterized by lower performances at specific cognitive tasks when motor symptoms are already present.