Search

Objective: Little is known about amyotrophic lateral sclerosis (ALS)‐nonspecific cognitive deficits – most notably memory disturbance – and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aβ and tau proteins with cognitive and motor phenotype in ALS. Methods: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aβ42, Aβ40, total tau (T‐tau), and phosphorylated tau (P‐tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype. Results: APOE‐E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non‐carriers) and lower CSF Aβ42 (−0.8 vs. 0.1, log‐transformed values) and Aβ42/40 ratio (−0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aβ42 levels, possibly reflecting cerebral Aβ deposition. While lower Aβ42/40 correlated with lower memory score (β = 0.20), Aβ42 positively correlated with both ALS‐specific (β = 0.24) and ALS‐nonspecific (β = 0.24) scores. Although Aβ42/40 negatively correlated with T‐tau (β = −0.29) and P‐tau181 (β = −0.33), we found an unexpected positive association of Aβ42 and Aβ40 with both tau proteins. Regarding motor phenotype, lower levels of Aβ species were associated with lower motor neuron (LMN) signs (Aβ40: β = 0.34; Aβ42: β = 0.22). Conclusions: APOE haplotype and CSF Aβ biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD‐like pathophysiological processes, but additional ALS‐specific mechanisms could be involved. [ABSTRACT FROM AUTHOR]

Background and purpose: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta‐analysis of NFL in ALS and FTD was performed. Methods: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated. Results: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences. Discussion: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed at estimating the prevalence of language impairment (LI) in a large, clinic‐based cohort of non‐demented amyotrophic lateral sclerosis (ALS) patients and assessing its underpinnings at motor and non‐motor levels. Methods: Non‐demented ALS patients (N = 348) underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), as well as an assessment of behavioural/psychiatric and motor‐functional features. The prevalence of LI was estimated based on the proportion of patients showing a performance below the age‐ and education‐adjusted cut‐off on the ECAS‐Language. Multiple regression models were run to assess the determinants of language functioning and impairment. Results: The prevalence of LI was 22.7%. 46.6% of the variance of ECAS‐Language scores remained unexplained, with only the ECAS‐Executive positively predicting them (p < 0.001; η2 = 0.07). Similarly, only a lower score on the ECAS‐Executive predicted a higher probability of a below cut‐off ECAS‐Language performance (p < 0.001). Spelling and Naming tasks were the major drivers of ECAS‐Language performance. Conclusions: This study suggests that, in non‐demented ALS patients, LI occurs in ≈23% of cases, is significantly driven by executive dysfunction but, at the same time, partially independent of it and is not associated with other motor or non‐motor features. [ABSTRACT FROM AUTHOR]