(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have
never been specifically analyzed according to the lateralization of motor impairment. In the present
study we investigated the cognitive performances of ALS patients to describe the relationship between
motor and cognitive dysfunction, according to site and side of disease onset. (2) Methods: Six-hundred
and nine ALS patients underwent a comprehensive neuropsychological evaluation at diagnosis in
Turin ALS Centre Tests included--mini-mental state examination (MMSE), frontal assessment battery
(FAB), trail-making test A/B (TMT A-B), digit span forward and backward (digit span FW/digit
span BW), letter fluency test (FAS), category fluency test (CAT), Rey auditory verbal learning test
(RAVLT), Babcock story recall test (BSRT), Rey-Osterrieth complex figure test (ROCFT),Wisconsin
card sorting test (WCST), Raven's coloured progressive matrices (CPM47). Cognitive performances of
patients, grouped by side and site of onset, were statistically compared using z-scores, as appropriate.
(3) Results: Bulbar patients and bilateral spinal onset patients (Sbil) were generally characterized by
lower cognitive performances in most neuropsychological tests, when compared to patients with
lateralized onset (right-side spinal onset, Sri and left-side spinal onset, Sle). Digit span backward and
visual memory task (ROCFT) median z-scores were significantly higher, reflecting a better cognitive
performance, in Sri patients when compared to bulbar/Sbil patients, while verbal memory tasks
(RAVLT and BRST) resulted in significantly higher scores in Sle patients. Our results are in keeping
with hemispheric functional lateralization of language and visuospatial abilities. (4) Conclusions:
In ALS patients, as in other neurodegenerative diseases, we found a direct relationship between
lateralized motor and cognitive features.
