Cognition and motor phenotypes in ALS: a retrospective study

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is phenotypically heterogeneous in motor manifestations, and the extent of upper vs. lower motor neuron involvement is a widespread descriptor. This study aimed to examine cognition across different ALS motor phenotypes.

Methods: ALS patients (N = 124) were classified as classical (N = 66), bulbar (N = 13), predominant-upper motor neuron (PUMN; N = 19), and predominant-lower motor neuron (PLMN; N = 26) phenotypes. Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and function with the ALS Functional Rating Scale-Revised (ALSFRS-R). Revised ALS-FTD consensus criteria were applied for cognitive/behavioral phenotyping.

Results: Defective ECAS-total scores were detected in all groups - bulbar: 15.4%, classical: 30.3%, PLMN: 23.1%, and PUMN: 36.8%. Classical and PUMN ALS patients performed worse than PLMN ones on ECAS-total, ALS-specific, Fluency, and Executive measures. No other difference was detected. Worse ASLFRS-R scores correlated with poorer ECAS-total scores in classical ALS patients.

Conclusions: Frontotemporal cognitive deficits are more prevalent in PUMN and classical ALS and linked to disease severity in the latter, but occur also in PLMN phenotypes.

Keywords: Amyotrophic lateral sclerosis; Cognitive impairment: Upper motor neuron; Frontotemporal degeneration; Lower motor neuron.