No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

Abstract

Background/Aims: A substantial proportion of amyotrophic lateral sclerosis (ALS) patients develop cognitive impairments. Longitudinal investigations of cognition in ALS have shown mixed results. While some authors report that cognitive performance remains stable as the disease progresses, others have found evidence for deterioration in various domains. Our objective was to investigate cognitive performance in ALS longitudinally, using the example of executive functions. Methods: 93 ALS patients and 73 age-, sex- and education-matched healthy controls underwent up to four neuropsychological evaluations, separated by 3- to 6-month intervals. We examined whether performance declined longitudinally on seven tests assessing various sub-components of executive functioning. Furthermore, we assigned an executive-performance-based ‘cognitive status' to each participant for every evaluation, examining whether cognitive deterioration (if present) was modulated by their baseline cognitive status and whether cognitive status changed over time. Results: Regardless of their cognitive status at baseline, ALS patients showed no significant decline in the sub-components of executive functioning. Conclusion: Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS.

Story of the ALS-FTD continuum retold: rather two distinct entities

“…Thus, ALS and FTD do not represent one entity in the sense that a single patient, for example, with ALS necessarily changes into a patient with FTD and vice versa, which is in line with the fact that cognitive performance does not necessarily decline in the course of ALS 14. This has major clinical implications as these minor cognitive impairments in ALS do not interfere with medical decision-making6 and thus have mostly no impact on the daily living of patients with ALS, whereas for patients with ALS with full-blown behavioural phenotype of bvFTD (ALS-bvFTD), the interference can be expected.…”

The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis

“…These kind of studies in patients with ALS are hampered by loss to follow-up due to progression of motor symptoms, including nocturnal hypoventilation or daytime hypercapnia due to respiratory insufficiency. [49][50][51] The latter complicates the interpretation of the nature of cognitive and behavioural changes in end-stage ALS. A future study in patients with early onset ALS (ie, disease duration <1 year) with longitudinal (eg, home-based) assessment of cognitive, behavioural and respiratory functions in late-stage ALS, may add relevant new information to the ongoing debate on the progression of cognitive deficits in ALS and the cognitive disease continuum between ALS and bv-FTD.…”

Functional reorganization during cognitive function tasks in patients with amyotrophic lateral sclerosis

“…Due to the nature of this proof-of-principle study, no far advanced ALS patients were included. Even though cognitive impairment seems to be stable during the course of the disease (26,27) and even may precede motor symptoms 28 ALS patients has already been demonstrated in previous studies (31,32), to reliably assess cognitive functioning in far advanced patients (33). However, above mentioned considerations regarding the translation of standard neuropsychological screening instruments into an eye-tracking format also apply when this modality of testing will be used.…”