Non-demented Amyotrophic Lateral Sclerosis Research Articles

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

Factors associated with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) alteration at time of diagnosis, in amyotrophic lateral sclerosis

BackgroundEdinburgh Cognitive and Behavioral ALS Screen (ECAS) is a validated assessment designed to screen cognitive functions and behavioral disorders in amyotrophic lateral sclerosis (ALS). Objective of this study is to determine the factors associated with ECAS impairment in a cohort of ALS patients without a co-morbid diagnosis of dementia, at the time of diagnosis. MethodsWe enrolled 71 non-demented ALS patient. We collected clinical and demographic data, ALS familiarity, analysis of the most commonly mutated genes in ALS, ALS Milano Torino Staging System and ALS Functional Rate Scale revised scores, progression rate; finally, we recorded whether symptoms onset involved spinal or bulbar area. The alteration of the ECAS was estimated based on age and education-adjusted-validated cut off for each of the items included in ECAS. A multivariable regression analysis was done. ResultsThe significant determinants of ECAS alterations were: bulbar onset in both ALS-specific test and total ECAS score; bulbar onset and familiarity in ALS-non-specific test; finally, familiarity and diagnosis delay in ALS-behavioral test. All the subjects carrying C9orf72 mutations had alteration of both total ECAS score and ALS-specific tests. DiscussionAt diagnosis, bulbar-onset ALS, family history, diagnosis delay and C9orf72 hexanucleotide repeat expansion may contribute to impairment of ECAS.

Emotional awareness in patients with amyotrophic lateral sclerosis.

It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS). Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status. Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤ .011), memory (p = .006), state-anxiety (p ≤ .013) and depression measures (p ≤ .010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤ .008). Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease.

Ecological validity of performance-based cognitive screeners in amyotrophic lateral sclerosis: preliminary evidence.

This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes. N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview). The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027). This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers.

An exploratory study on counterfactual thinking in amyotrophic lateral sclerosis.

This study aimed at exploring (1) the motor and non-motor correlates of counterfactual thinking (CFT) abilities in non-demented amyotrophic lateral sclerosis (ALS) patients and (2) the ability of CFT measures to discriminate these patients from healthy controls (HCs) and patients with and without cognitive impairment. N = 110 ALS patients and N = 51 HCs were administered two CFT tasks, whose sum, resulting in a CFT Index (CFTI), was addressed as the outcome. Patients further underwent an in-depth cognitive, behavioral, and motor-functional evaluation. Correlational analyses were run to explore the correlates of the CFTI in patients. Logistic regressions were performed to test whether the CFTI could discriminate patients from HCs. The CFTI was selectively associated (p ≤ 0.005) with fluency and memory subscales of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), but not with other variables. CFTI scores discriminated patients from HCs (p < 0.001) with high accuracy (82%), but not patients with a normal vs. defective performance on the ECAS-Total. CFT measures in non-demented ALS patients were associated with verbal fluency and memory functions, and they were also able to discriminate them from HCs.

Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients

BackgroundThe present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients.MethodsN = 88 ALS patients without frontotemporal dementia were assessed for FI—Katz’s Basic ADL Scale (BADL) and Lawton-Brody’s Instrumental ADL Scale (IADL)—, cognition—Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders—i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King’s and Milano-Torino stages.ResultsHigher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features—as measured by the Dimensional Apathy Scale (DAS)—were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without.DiscussionAmong non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.

Memory-guided navigation in amyotrophic lateral sclerosis

BackgroundPrevious studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients.MethodsWe conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research (“starmaze”) that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test).ResultsPatients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups (p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups (p ≥ 0.238).ConclusionsThis study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.

Clinical usability of the Story-Based Empathy Task (SET) in non-demented ALS patients.

This study aimed at assessing the clinical usability of the Story-Based Empathy Task (SET) in non-demented amyotrophic lateral sclerosis (ALS) patients. N = 106 non-demented ALS patients and N = 101 healthy controls (HCs) were administered the SET, which includes three subtests assessing Emotion Attribution (SET-EA), Intention Attribution (SET-IA) and causal inference (SET-CI) - the latter being a control task. Patients also underwent the Reading the Mind in the Eyes Test (RMET), the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and a thorough behavioural and motor-functional evaluation. The diagnostics of the SET-EA and -IA were tested against a defective performance on the RMET. The association between SET subtests and cognitive/behavioural outcomes was examined net of demographic and motor-functional confounders. Case-control discrimination was explored for each SET subtest. Demographically adjusted SET-EA and -IA scoresaccurately detected defective RMET performances at the optimal cutoffs of <3.04 (AUC = .84) and <3.61 (AUC = .88), respectively. By contrast, the SET-CI performed poorly in doing so (AUC = .58). The SET-EA converged with the RMET, as well as with ECAS-Executive and -Memory scores, whilst the SET-IA was unrelated to cognitive measures (including the RMET); the SET-CI was related to the ECAS-Language the ECAS-Executive. SET subscores were unrelated to behavioural outcomes. Only the SET-EA discriminated patients from HCs. The SET as a whole should not be addressed as a social-cognitive measure in this population. At variance, its subtest tapping on emotional processing - i.e., the SET-EA - is recommended for use as an estimate of social-cognitive abilities in non-demented ALS patients.

Prevalence and determinants of language impairment in non-demented amyotrophic lateral sclerosis patients.

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. 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. 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. 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.

Validity and diagnostics of the Reading the Mind in the Eyes Test (RMET) in non-demented amyotrophic lateral sclerosis (ALS) patients.

The aim of this study was to explore the construct validity and diagnostic properties of the Reading the Mind in the Eyes Test (RMET) in non-demented patients with amyotrophic lateral sclerosis (ALS). A total of 61 consecutive patients and 50 healthy controls (HCs) were administered the 36-item RMET. Additionally, patients underwent a comprehensive assessment of social cognition via the Story-Based Empathy Task (SET), which encompasses three subtests targeting Causal Inference, Emotion Attribution (SET-EA), and Intention Attribution (SET-IA), as well as global cognitive [the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and behavioral screening [the Frontal Behavioral Inventory (FBI); the Dimensional Apathy Scale (DAS); the Beck Depression Inventory (BDI); and the State and Trait Anxiety Inventory-Y]. The construct validity of the RMET was tested by regressing it within a stepwise model that encompassed as predictors the abovementioned cognitive and behavioral measures, covarying for demographic and motor confounders. Receiver-operating characteristics (ROC) analyses allowed exploring intrinsic and post-test properties of the RMET both in discriminating patients from HCs and in identifying patients with a defective SET-EA performance. The RMET was solely predicted by the SET-EA (p = 0.003) and SET-IA (p = 0.005). RMET scores showed high accuracy both in discriminating patients from HCs (AUC = 0.81) and in identifying patients with a defective SET-EA score (AUC = 0.82), with adequate-to-optimal both intrinsic and post-test properties. The RMET is a convergently and divergently valid measure of affective social cognition in non-demented ALS patients, also featuring optimal intrinsic and post-test diagnostic properties in both case-control and case-finding scenarios.

Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS.

To explore whether the combined analysis of motor and bulbar region of M1 on susceptibility-weighted imaging (SWI) can be a valid biomarker for amyotrophic lateral sclerosis (ALS). Thirty-two non-demented ALS patients and 35 age- and gender-matched healthy controls (HC) were retrospectively recruited. SWI and 3D-T1-MPRAGE images were obtained from all individuals using a 3.0-T MRI scan. The bilateral posterior band of M1 was manually delineated by three neuroradiologists on phase images and subdivided into the motor and bulbar regions. We compared the phase values in two groups and performed a stratification analysis (ALSFRS-R score, duration, disease progression rate, and onset). Receiver operating characteristic (ROC) curves were also constructed. ALS group showed significantly increased phase values in M1 and the two subregions than the HC group, on the all and elderly level (p < 0.001, respectively). On all-age level comparison, negative correlations were found between phase values of M1 and clinical score and duration (p < 0.05, respectively). Similar associations were found in the motor region (p < 0.05, respectively). On both the total (p < 0.01) and elderly (p < 0.05) levels, there were positive relationships between disease progression rate and M1 phase values. In comparing ROC curves, the entire M1 showed the best diagnostic performance. Combining motor and bulbar analyses as an integral M1 region on SWI can improve ALS diagnosis performance, especially in the elderly. The phase value could be a valuable biomarker for ALS evaluation. • Integrated analysis of the motor and bulbar as an entire M1 region on SWI can improve the diagnosis performance in ALS. • Quantitative analysis of iron deposition by SWI measurement helps the clinical evaluation, especially for the elderly patients. • Phase value, when combined with the disease progression rate, could be a valuable biomarker for ALS.

A preliminary comparison between ECAS and ALS-CBS in classifying cognitive-behavioural phenotypes in a cohort of non-demented amyotrophic lateral sclerosis patients.

To define the presence and type of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS), different screening tools have been created. Currently, the most used screening tests are the Edinburgh cognitive and behavioural ALS screen (ECAS) and the ALS cognitive behavioural screen (ALS-CBS). The objective of this study was to compare the ability of ECAS and ALS-CBS in classifying non-demented ALS patients according to Strong criteria. One-hundred and fifty-four in- and out-patients with an age > 18 and a definite or probable ALS diagnosis were recruited between September 2019 and February 2020 at NeMO Clinical Centre and at Istituto Auxologico Italiano in Milan and underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioural Screen (ALS-CBS). Exclusion criteria involved patients with a diagnosis of FTD, with a severe cognitive deterioration and/or an important behavioural impairment, with a significant psychiatric disorder or with the co-presence of another significant illness. The distribution of patients according to Strong criteria was different for ECAS and ALS-CBS and the degree of agreement between the two tests in terms of Cohen's Kappa coefficient resulted equal to 0.2047 with a 95% confidence limits interval between 0.1122 and 0.2973. This study for the first time compares the ability of ECAS and ALS-CBS in stratifying ALS patients. Further studies will be conducted to better understand the reasons underlying the differences between these two tests in classifying the different subtypes of fronto-temporal dysfunction in ALS.

Hippocampal connectivity in Amyotrophic Lateral Sclerosis (ALS): more than Papez circuit impairment

Emerging evidence suggests that memory deficit in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with varying impairment of motor abilities and cognitive profile, may be independent from executive dysfunction. Our multimodal magnetic resonance imaging (MRI) approach, including resting state functional MRI (RS-fMRI), diffusion tensor imaging (DTI) and voxel-based morphometry (VBM), aimed to investigate structural and functional changes within and beyond the Papez circuit in non-demented ALS patients (n = 32) compared with healthy controls (HCs, n = 21), and whether these changes correlated with neuropsychological measures of verbal and non-verbal memory. We revealed a decreased functional connectivity between bilateral hippocampus, bilateral parahippocampal gyri and cerebellum in ALS patients compared with HCs. Between-group comparisons revealed white matter abnormalities in the genu and body of the corpus callosum and bilateral cortico-spinal tracts, superior longitudinal and uncinate fasciculi in ALS patients (p < .05, family-wise error corrected). Interestingly, changes of Digit Span forward performance were inversely related to RS-fMRI signal fluctuations in the cerebellum, while changes of both episodic and visual memory scores were inversely related to mean and radial diffusivity abnormalities in several WM fiber tracts, including middle cerebellar peduncles. Our findings revealed that ALS patients showed significant functional and structural connectivity changes across the regions comprising the Papez circuit, as well as more extended areas including cerebellum and frontal, temporal and parietal areas, supporting the theory of a multi-system pathology in ALS that spreads from cortical to subcortical structures.

Papez Circuit Gray Matter and Episodic Memory in Amyotrophic Lateral Sclerosis and Behavioural Variant Frontotemporal Dementia.

Amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia are two different diseases recognized to overlap at clinical, pathological and genetic characteristics. Both conditions are traditionally known for relative sparing of episodic memory. However, recent studies have disputed that with the report of patients presenting with marked episodic memory impairment. Besides that, structural and functional changes in temporal lobe regions responsible for episodic memory processing are often detected in neuroimaging studies of both conditions. In this study, we investigated the gray matter features associated with the Papez circuit in amyotrophic lateral sclerosis, behavioural variant frontotemporal dementia and healthy controls to further explore similarities and differences between the two conditions. Our non-demented amyotrophic lateral sclerosis patients showed no episodic memory deficits measured by a short-term delayed recall test while no changes in gray matter of the Papez circuit were found. Compared with the amyotrophic lateral sclerosis group, the behavioural variant frontotemporal dementia group had lower performance on the short-term delayed recall test and marked atrophy in gray matter of the Papez circuit. Bilateral atrophy of entorhinal cortex and mammillary bodies distinguished behavioural variant frontotemporal dementia from amyotrophic lateral sclerosis patients as well as atrophy in left cingulate, left hippocampus and right parahippocampal gyrus. Taken together, our results suggest that sub-regions of the Papez circuit could be differently affected in amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia.

Behavioral manifestations in a Brazilian non-demented C9orf72-negative ALS population

Cognitive decline and behavioral changes are common features in amyotrophic lateral sclerosis (ALS) and imply worse prognosis as well as increased disease burden for patients and caregivers. Currently, there is a lack of studies regarding behavioral profile in Brazilian ALS cohorts. We assessed the prevalence and profile of behavioral impairment (ALSbi) in a Brazilian non-demented C9orf72-negative ALS cohort according to broad behavioral assessment and the latest consensus. Among 76 initially recruited consecutive ALS patients, 70 were included, including seven ALS type 8 (VAPB-related ALS) individuals. Patients with Frontotemporal Dementia (FTD) diagnosis were excluded. Sixteen ALS patients (23%) were diagnosed as ALSbi. Among ALS type 8 individuals, 2 (28.6%) were diagnosed as ALSbi. Neuropsychiatric Inventory Questionnaire (NPI) total scores did positively correlate with age, but not with other demographic or clinical data. Apathy was the most prevalent finding in the ALSbi subgroup, although the prevalence (20%) was smaller than reported in previous literature. Dysphoria and anxiety were also prevalent findings in the whole ALS cohort. Future studies with larger cohorts and validated ALS-specific tools are needed in order to expand our knowledge.

Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS

ObjectiveApproximately 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...

Microstructural correlates of Edinburgh Cognitive and Behavioural ALS Screen (ECAS) changes in amyotrophic lateral sclerosis

Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was designed for testing patients with amyotrophic lateral sclerosis (ALS), a multi-system neurodegenerative disease characterized by progressive physical disability. In this study, we aim to explore the potential brain microstructural substrates associated with performance on ECAS in the early stages of ALS, using a whole-brain tract-based spatial statistics diffusion tensor imaging approach. Thirty-six non-demented ALS patients, assessed using ECAS, and 35 age-, sex- and education-matched healthy controls underwent magnetic resonance imaging at 3 Tesla. The ALS patients showed decreased fractional anisotropy (FA) in the cortico-spinal tracts and corpus callosum (CC) and significant association between verbal fluency score, among ALS-specific ECAS scores, and FA measures in several long association fiber tracts in the frontal, temporal and parietal lobes. Furthermore, the ALS non-specific total score was inversely related to axial diffusivity (AD) in the mediodorsal nucleus of the thalamus, with more extended areas of correlation in the CC, when considering only the memory subscore. Our results point towards microstructural degeneration across motor and extra-motor areas in ALS, underlining that alterations in verbal fluency performances may be related to impairment of frontotemporal connectivity, while alterations of memory may be associated with damage of thalamocortical circuits.

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses.

Resting-state functional magnetic resonance imaging has been playing an important role in the study of amyotrophic lateral sclerosis (ALS). Although functional connectivity is widely studied, the patterns of spontaneous neural activity of the resting brain are important mechanisms that have been used recently to study a variety of conditions but remain less explored in ALS. Here we have used fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) to study the regional dynamics of the resting brain of nondemented ALS patients compared with healthy controls. As expected, we found the sensorimotor network with changes in fALFF and ReHo, and also found the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) altered and the cerebellum, although no structural changes between ALS patients and controls were reported in the regions with fALFF and ReHo changes. We show an altered pattern in the spontaneous low-frequency oscillations that is not confined to the motor areas and reveal a more widespread involvement of nonmotor regions, including those responsible for cognition.

Episodic memory and learning rates in amyotrophic lateral sclerosis without dementia

In amyotrophic lateral sclerosis (ALS), memory deficits may be primary or secondary to executive dysfunction. We assessed episodic memory and executive function of nondemented ALS patients, comparing episodic memory profiles and learning rates of ALS patients with those of mild cognitive impairment (MCI) subjects and cognitively healthy controls (HC). In a multidisciplinary tertiary centre for motor neuron disease, 72 nondemented ALS patients, 57 amnestic MCI (aMCI), 89 single non amnestic MCI with compromised executive functions (dysexecutive MCI), and 190 HC were enrolled. They were screened using the Frontal Assessment Battery and Mini Mental State Examination. Episodic memory performances and learning rates were tested using the Rey Auditory Verbal Learning Test (RAVLT). Episodic memory dysfunction (immediate recall) was found in 14 ALS patients (19.4%). The ALS group had lower performance than HC on immediate recall, without differences in learning rate, and better performance than aMCI subjects on all RAVLT measures. Compared to dysexecutive MCI subjects, ALS patients had only better verbal learning abilities. ALS patients with executive dysfunction had a lower score on immediate and delayed recalls, verbal learning, and primacy effect than ALS patients without executive dysfunction. The immediate recall among couples of diagnostic groups differed in a statistically significant way except for the ALS/dysexecutive MCI groups. In ALS patients, episodic memory performances and learning rates appeared to be better than in aMCI subjects and similar to those with dysexecutive MCI, suggesting also a secondary functional damage due to executive impairment.

Radial diffusivity as an imaging biomarker for early diagnosis of non-demented amyotrophic lateral sclerosis.

To explore the sensitivity of potential DTI-based biomarkers in detecting microstructural changes for whole-brain white matter in early stage amyotrophic lateral sclerosis (ALS), analyze the relationship between the DTI indices and disease status, and further clarify potential brain regions for disease monitoring and clinical assessment. Thirty-three non-demented ALS patients and 32 age- and gender-matched subjects participated in this study. DTI data were acquired via 3.0T MRI scanner. Maps of diffusion-related indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were obtained. Tract-based spatial statistics (TBSS) were used to investigate whole-brain white matter changes of each index. Correlation analyses between both brain-wide and volume-of-interest (VOI)-wide white matter alterations and clinical factors including ALSFRS-R scores, disease duration, and progression rate were performed. Compared to healthy subjects, ALS patients showed significantly increased RD, MD and reduced FA, mainly along the corticospinal tract (CST) and the body of corpus callosum (CC). Increases in RD were broader than decreases in FA, in CST of both hemispheres. Meanwhile, involvement of several extra-motor regions was also revealed by RD. Significant positive correlation between ALSFRS-R scores and FA, negative correlation between ALSFRS-R and RD were found in left CST. RD may be the most sensitive biomarker for the detection of early demyelination of white matter. Both RD and FA may serve as objective biomarkers for disease severity assessment. CST may be the most affected brain region in non-demented ALS. • Changes in RD were broader than those in FA in bilateral CST. • Involvement of extra-motor regions was uncovered by RD. • FA and RD in CST were related to ALSFRS-R scores.