Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS.
J Neurol Neurosurg Psychiatry
; 91(2): 149-157, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31515300
ABSTRACT
OBJECTIVE:
Approximately 35% of patients with amyotrophic lateral sclerosis (ALS) exhibit mild cognitive deficits in executive functions, language and fluency, without dementia. The precise pathology of these extramotor symptoms has remained unknown. This study aimed to determine the pathological correlate of cognitive impairment in patients with non-demented ALS.METHODS:
In-depth neuropathological analysis of 27 patients with non-demented ALS who had undergone cognitive testing (Edinburgh Cognitive and Behaviour ALS Screen (ECAS)) during life. Analysis involved assessing 43 kDa Tar-DNA binding protein (TDP-43) accumulation in brain regions specifically involved in executive functions, language functions and verbal fluency to ascertain whether functional deficits would relate to a specific regional distribution of pathology.RESULTS:
All patients with cognitive impairment had TDP-43 pathology in extramotor brain regions (positive predictive value of 100%). The ECAS also predicted TDP-43 pathology with 100% specificity in brain regions associated with executive, language and fluency domains. We also detected a subgroup with no cognitive dysfunction, despite having substantial TDP-43 pathology, so called mismatch cases.CONCLUSIONS:
Cognitive impairment as detected by the ECAS is a valid predictor of TDP-43 pathology in non-demented ALS. The profile of mild cognitive deficits specifically predicts regional cerebral involvement. These findings highlight the utility of the ECAS in accurately assessing the pathological burden of disease.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Verbal
/
Córtex Cerebral
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Proteínas de Ligação a DNA
/
Função Executiva
/
Disfunção Cognitiva
/
Esclerose Lateral Amiotrófica
/
Transtornos da Linguagem
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Neurol Neurosurg Psychiatry
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido