Perfil de linguagem no espectro de doenças do neurônio motor: estudo cognitivo-comportamental

Abstract

Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (eALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial ALS type 8 (ALS8), linked to p.P56S VAPB mutation, remains unclear. The prognostic value of language impairment in this population remains unknown. This PhD thesis is composed of two studies: 1) Comparison of language profiles between sALS and ALS-8 patients and 2) Prognostic analysis of language deficits in ALS patients. In study 1, three groups of participants were included: 1) patients with sALS (n = 20); 2) patients with familial ALS-8 (n = 22) and 3) healthy controls (n = 21). The groups were matched by age, sex and education. All participants underwent an extensive language battery, including oral language comprehension and production items from the Boston Diagnostic Aphasia Examination (BDAE), the reduced Token test, letter fluency (FAS), categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery (CSMRB) and an analysis of narrative discourse. We also applied the Addenbrooke Cognitive Examination - Revised Version (ACE-R) and the Hospital Anxiety and Depression Scale (HADS). Patients also underwent the ALS Functional Rating Scale-Revised (ALSFRS-R). Compared to controls, patients with sALS and ALS-8 presented impaired performance in the comprehension and production of oral language and inadequate speech cohesion. sALS and ALS8 did not differ on any language measure. There was no correlation between language scores and ALSFRS-R and HADS. Patients with ALS-8 have language deficits similar to sALS, and these deficits are independent of motor features. In the second stage of this doctorate (Study 2), the prognostic value (in terms of functional decline) of the language alterations observed in ALS and ALS8 was analyzed. The functional scale was used as the outcome variable The ACE-R´s memory sub-item was able to predict the rate of progression of the fine motor subscore (R2 = 0.625, p<0.001), and the task letter fluency index and the item eating from CBI test were able to predict functional worsening in the motor subscore (R2 = 0.573, p = 0.002) in sALS group. In the ALS8 group, the repeated words subitem of the logical sequence test and Boston naming phonologic cue were able to predict the functional worsening of the total ALSFRS-R score (R2 = 0.600, p<0.001) and of the motor subscore (R2 =0.506, p<0.001), both from progression rate. These results add new findings to the emerging evidence showing that ALS-8 has prominent non-motor features. Our data suggest that language decline over time may have prognostic value in cases of sALS and ALS8.