A comparative study of cognitive and behavioral profiles between sporadic and type 8 amyotrophic lateral sclerosis

Abstract

Introduction/AimsAmyotrophic lateral sclerosis (ALS) type 8 (ALS8) is caused by VAPB gene mutations. The differences between neuropsychological and behavioral profiles of patients with sporadic ALS (sALS) and those with ALS8 are unclear. We aimed to compare cognitive performance and behavioral aspects between sALS and ALS8 patients.MethodsOur study included 29 symptomatic ALS8 patients (17 men; median age 49 years), 20 sALS patients (12 men; median age 55 years), and 30 healthy controls (16 men; median age 50 years), matched for sex, age, and education. Participants underwent neuropsychological assessments focused on executive functions, visual memory, and facial emotion recognition. Behavioral and psychiatric symptoms were evaluated using the Hospital Anxiety and Depression Scale and the Cambridge Behavioral Inventory.ResultsClinical groups (sALS and ALS8) exhibited lower global cognitive efficiency and impaired cognitive flexibility, processing speed, and inhibitory control compared with controls. ALS8 and sALS showed similar performance in most executive tests, except for poorer verbal (lexical) fluency in those with sALS. Apathy, anxiety, and stereotypical behaviors were frequent in both clinical groups.DiscussionsALS and ALS8 patients demonstrated similar deficits in most cognitive domains and had comparable behavioral profiles. These findings should be considered in the care of patients.

Memory for emotional information in sporadic and Type 8 amyotrophic lateral sclerosis.

“…Considering the findings from the neuropsychological assessment, individuals with sALS and ALS8 showed significantly lower performances on both MMSE and ACE-R than healthy controls but showed indistinguishable performances relative to healthy controls on FERT. Taken together, these findings are consistent with prior data indicating that similar neuropsychological deficits are produced by sALS and ALS8 (de Alcântara et al, 2023). More importantly, however, the current findings suggest that while individuals with sALS and ALS8 have spared memory for negative information, they have a reduced capacity to recognize positive information, a pattern that is apparently not detected by metacognitive mechanisms and seems to be unrelated to anxiety and depression symptoms.…”

“…According to current cognitive neuroscience models, the impact of valence on memory involves mainly regions of the prefrontal cortex, while the impact of arousal involves mainly structures of the amygdala (Kensinger & Corkin, 2004; Kensinger & Kark, 2018). Thus, considering the well-documented dysfunctions in prefrontal regions caused by sALS (Agosta et al, 2016; Ishaque et al, 2022; Schuster et al, 2014) and the recently shown executive dysfunctions caused by ALS8 (de Alcântara et al, 2019, 2023), a potential interpretation for the current findings is that prefrontal and executive dysfunctions may have produced the current reduction in recognition of positive valence stimuli. Although speculative, this is an interesting hypothesis to be approached by future neuroimaging studies on ALS and emotional memory.…”

“…The genetic mutation VAPB causes a type of ALS characterized by significant impairment of lower motor neurons, tremors, autonomic dysfunction, and abdominal protrusion, namely, ALS Type 8 (ALS8; Kosac et al, 2013; Nunes Gonçalves et al, 2021; Trilico et al, 2020). As in sALS, cognitive impairments have been observed in patients with ALS8, which include deficits in cognitive flexibility, processing speed, and inhibitory control (de Alcântara et al, 2019, 2023). Recent neuroimaging data, however, shows that sALS produces more widespread cortical atrophy than ALS8 (Leoni et al, 2022) and raises the question of whether more fine-grained aspects of episodic memory, such as its interaction with emotion, are differentially affected in patients with ALS8 relative to patients with sALS.…”

Language impairment in sporadic and familial (type 8) amyotrophic lateral sclerosis: A comparative study

“…All participants had Portuguese as their primary language. Some of the data used in the current study were collected as part of an earlier study 23 …”

“…Cognitive and behavioral disorders have been recently described in ALS8, 20,21 with patients demonstrating subtle executive deficits, mainly in tasks of inhibitory control and flexibility 22,23 . Previous studies have demonstrated cognitive and linguistic changes in fALS with mutations such as TARDBP , UBQLN2 , VCP , FUS , SOD1 , and C9ORF72 , 24 for example, motor neuron disease (MND) patients with a TARDBP mutation showed greater impairment in action and noun naming compared to healthy controls and MND patients without a TARDBP mutation 25 .…”