The Characteristics of Cognitive Impairment in ALS Patients Depend on the Lateralization of Motor Damage

Abstract

(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.

Cognition and motor phenotypes in ALS: a retrospective study

“…As to the associations between ALSFRS-R and ECAS scores, since the latter controls for motor disabilities [ 15 ], it is likely to reflect an actual co-variance of motor and cognitive function. This is in line with evidence on (1) a progressive cognitive decline with advancing motor impairment [ 27 ] and (2) the emerging picture of cognition being related to motor features — e.g., lateralization of motor damage [ 28 ] and hyperexcitability of motor cortices [ 29 ]. According to the present study, such associations would emerge for classical ALS only, possibly due to the fact that this phenotype entails a pervasive involvement of the motor system [ 2 ].…”

Upper motor neuron dysfunction is associated with the presence of behavioural impairment in patients with amyotrophic lateral sclerosis

“…According to some authors, cognitive and behavioural impairment progresses in parallel with the extension of motor neuron disease, being more marked in patients with a bulbar onset [3], reflecting the spreading mechanism of the TDP-43 pathological misfolding and accumulation [26]. A recent study pointed out that the characteristics of cognitive impairment depend on the lateralization of motor damage, with bilateral spinal onset patients performing worse in language and visuospatial tasks compared to patients with lateralized right or left spinal onset [27]. Few studies instead have investigated the possible correlation between the amount of UMN or LMN involvement and the presence of neuropsychological deterioration.…”

Potential role of vitamin D levels in amyotrophic lateral sclerosis cognitive impairment

“…In Cox regression model, Chi: 7.78 and p value: 0.02. X-axis: disease duration in months (for alive patients, we considered the 15th October 2022 as censored data; y-axis: percentage of survival over time correlation between low vitamin D values and worse overall performance perhaps related to more compromised patients globally [52]. The results of the Corrected Raven's Standard Progressive Matrices test were also confirmed in patients classified as rapidly progressing and in patients with a severe deficit of vitamin D (< 10 ng/ml), thus resulting in the test being most correlated to hypovitaminosis D. The apparent predominance of some cognitive functions in a subgroup of female patients could be attributable to gender-related neurobiological characteristics, including the different hormonal structure and polymorphic variants in the vitamin D receptor [53,54], that negatively influence the neurotrophic factors activity.…”