Background and Aims:

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.

Methods:

Patients were diagnosed according to El Escorial's revised criteria. Kings’ staging and genetic analysis at the time of cognitive testing were collected for all patients. ALS patients underwent a neuropsychological battery selected according to the ALS-FTD Consensus Criteria.

Comparisons were performed for King’s stage, independently from their level of cognitive status; for cognitive tests merging the intermediate cognitive categories, and for the number of ALSC9+ vs. ALSC9- cases who showed impairment in each neuropsychological domain.

Results:

Of 741 ALS patients (2010-2018) ALSC9+ patients had significantly lower scores in tests exploring executive functions and verbal memory both when classified as cognitively normal and when diagnosed in the intermediate cognitive categories. 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. The behavioral function was comparably impaired in the two cohorts.

Conclusions:

According to our data, it is conceivable that in some ALSC9+ patients a poor cognitive performance is already present in the early motor stages of the disease. Longitudinal studies are necessary to clarify whether this subclinical cognitive impairment in ALSC9+ patients will evolve to clinically overt dementia over time.