scholarly journals An Evaluation of Empirical Approaches for Defining Cognitive Impairment in Amyotrophic Lateral Sclerosis

2020 ◽  
Author(s):  
Corey T. McMillan ◽  
Joanne Wuu ◽  
Katya Rascovsky ◽  
Stephanie Cosentino ◽  
Murray Grossman ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cognitive Impairment ◽  
Quantile Regression ◽  
Statistical Method ◽  
North American ◽  
Healthy Adults ◽  
Substantial Impact ◽  
The University ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractImportanceAmyotrophic lateral sclerosis (ALS) is a multi-system disorder characterized primarily by motor neuron degeneration, but may be accompanied by cognitive dysfunction. Statistically appropriate criteria for establishing cognitive impairment (CI) in ALS are lacking.ObjectiveDefine thresholds for CI in ALS using quantile regression (QR) that accounts for age and education in a North American (NAmer) cohort.DesignQR of cross-sectional data from a multi-center NAmer cohort of healthy adults was used to model the 5th percentile of cognitive scores on the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). The QR approach was compared to a traditional 2 standard deviation (SD) cut-off approach using the same NAmer cohort (2SD-NAmer) and to existing UK-based normative data derived using the 2SD approach (2SD-UK) to assess the impact of cohort selection and statistical model in identifying CI ALS patients.Participants269 healthy adults from NAmer, recruited by the University of Pennsylvania (PENN; N=82), the University of Miami through the CRiALS study (CRiALS; N=40), and the Canadian ALS Neuroimaging Consortium (CALSNIC; N=147) were included to establish ECAS thresholds for defining CI. We then evaluated the frequency of CI in 182 ALS patients from PENN.Main OutcomesWe defined two new sets of normative thresholds, based on NAmer heathy adult performance, for each ECAS domain score and the composite scores using QR and 2SD statistical approaches. We then applied the 2SD-NAmer and QR-NAmer, as well as the previously established and widely-used 2SD-UK, thresholds to evaluate the frequency of CI in ALS patients.ResultsQR-NAmer models revealed that increased age and reduced educational attainment negatively impact cognitive performance on the ECAS. Based on the QR-NAmer normative cutoffs, the prevalence of CI in the 182 PENN ALS patients was 15.9% for ECAS ALS-Specific and 15.4% for ECAS Total. These estimates are more conservative than estimates ranging from 15.4%-34.6% impaired based on 2SD approaches.Conclusions and RelevanceThis report establishes normative thresholds for using ECAS to identify whether ALS patients in the NAmer population have CI. The choice of statistical method and normative cohort has a substantial impact on defining CI in ALS.Key PointsQuestionHow to define cognitive impairment (CI) in amyotrophic lateral sclerosis (ALS) using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)?FindingsAge- and education-adjusted quantile regression (QR) yields thresholds for defining CI that differ meaningfully from those derived from parametric methods without age- and education-adjustment. Thresholds also differ between UK and North American cohorts. Applying our North American-based QR norms to an American ALS cohort at a single center identified CI based on ECAS performance in ∼16% patients, compared to 15.4%-34.6% patients using other approaches.MeaningThe choice of statistical method and normative cohort has a substantial impact on defining CI in ALS.

A-151 Cognitive Impairment in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 36 (6) ◽  
pp. 1205-1205
Author(s):  
Etiane Navarro ◽  
Charles J Golden
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cognitive Impairment ◽  
Literature Review ◽  
Cognitive Impairments ◽  
Empirical Literature ◽  
Sporadic Als ◽  
Neuropsychological Assessments ◽  
Familial Als ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Objective Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease caused by degeneration of the upper and lower motor neurons. This literature review examines the recurring etiology of cognitive impairments in ALS through empirical literature. The current study explores ALS across different subtypes and potential cognitive impairments. Two classifications are primarily examined ALS, and ALS with frontotemporal dementia (ALS-FTD). Involving three categories: familial inheritance pattern, genetic mutation, or sporadic. Neuropsychological studies affirm cognitive impairments in individuals diagnosed with ALS and ALS-FTD. Data Selection Data was culled from the American Psychological Association (PsycInfo), PubMed, Google Scholar. Terms used in this literature review include cognitive impairment in ALS and ALS-FTD, executive function deficiencies in ALS, neuropsychology in ALS, neuropsychological deficits in ALS, neuropsychological assessments for ALS, cognitive impairments in familial ALS, genetic ALS, and sporadic ALS, familial ALS, sporadic ALS, genetic mutations involved in ALS. Search dates December 20–23 of 2020 and March 3–4 of 2021. A total of 40 studies were examined. Data Synthesis ALS-patients demonstrate a significant cognitive impairment. However, influencing comorbidities accompanying the disease may be contributing to these impairments. Researchers employed neuroimaging and neuropsychological batteries to further understand influencing factors involved in ALS and cognition. Conclusions Researchers now understand ALS as a multi-symptomatic disorder and acknowledge the presence of cognitive impairments at various encased levels. There are limitations in neuropsychological batteries that accommodate for executive dysfunctions observed in ALS patients. Future studies should explore neuropsychological assessments that accommodate for motor deficits and dysarthria when assessing cognitive impairment in ALS patients.

scholarly journals Practical Measures for Dealing With the Struggles of Nurses Caring for People With Amyotrophic Lateral Sclerosis Comorbid With Cognitive Impairment in Japan

2021 ◽  
Vol 12 ◽  
Author(s):  
Mitsuko Ushikubo ◽  
Emiko Nashiki ◽  
Tadahiro Ohtani ◽  
Hiromi Kawabata
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cognitive Impairment ◽  
Early Stage ◽  
Care Delivery ◽  
Care Quality ◽  
Daily Lives ◽  
Free Writing ◽  
Group Interviews ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which there is currently no cure. This study aimed to explore the situations with which nurses struggled, their implemented practical measures, and the challenges they experienced when caring for patients with ALS comorbid with cognitive impairment (hereinafter, targeted patients). In this qualitative study, we conducted a survey with nurses (n = 121) experienced in caring for ALS patients; the survey contained a free-writing section in which participants described their struggles regarding care delivery for these patients. To collect data on practical measures that nurses had already implemented or wanted to propose regarding care delivery for the targeted patients, we conducted four focus group interviews (n = 22). We used a qualitative inductive approach to extract the categories. Fifty-eight nurses (49.6%) completed the free-writing survey section. The situations in which nurses struggled in care for the targeted patients were organized into three categories: “Patients’ strong persistency on specific requirements for nursing assistance in their daily lives,” “Patients’ problematic behaviors toward nurses,” and “Struggles in communicating with and understanding patients’ wishes.” Nurses reported these situations as stressful, and they affected care quality. The practical measures implemented when caring for the targeted patients were organized into five categories: “Cognitive impairment assessment,” “Care delivery to deal with patients’ strong persistency on specific requirements for assistance in their daily lives,” “Communication,” “Supporting the decision-making process,” and “Collaboration between the hospital and the community.” Multidisciplinary collaboration in the hospital, and collaboration between the hospital and the community from an early stage is necessary to share the results of the assessment and diagnosis of cognitive impairment. Our evidence underlines that guideline and care manual establishment may lead to improved care delivery and to the unification of care deliveries to respond to patients’ strong persistency.

scholarly journals The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Ran An ◽  
Yan Li ◽  
Xianghua He ◽  
Cheng Li ◽  
Xin Li ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuropathic Pain ◽  
Disease Duration ◽  
Rating Scale ◽  
Nociceptive Pain ◽  
Southwestern China ◽  
Substantial Impact ◽  
Als Patients ◽  
Normal Controls ◽  
Lateral Sclerosis

Background. Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods. Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results. 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) ( p = 0.193 ). DN4 score ⩾ 4 was found in three ALS patients and one control ( p = 0.480 ). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) ( p < 0.001 ) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain ( p = 0.041 , 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients’ mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions. Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients’ mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score ⩾ 4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

scholarly journals Cognitive and Behavioral Manifestations in ALS: Beyond Motor System Involvement

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 624
Author(s):  
Robert Rusina ◽  
Rik Vandenberghe ◽  
Rose Bruffaerts
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cognitive Impairment ◽  
Frontotemporal Dementia ◽  
Clinical Manifestations ◽  
Executive Dysfunction ◽  
Motor Disorder ◽  
Behavioral Impairment ◽  
Caregiver Support ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) has long been considered to be a purely motor disorder. However, it has become apparent that many ALS patients develop cognitive and behavioral manifestations similar to frontotemporal dementia and the term amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) is now used in these circumstances. This review is intended to be an overview of the cognitive and behavioral manifestations commonly encountered in ALS patients with the goal of improving case-oriented management in clinical practice. We introduce the principal ALS-FTSD subtypes and comment on their principal clinical manifestations, neuroimaging findings, neuropathological and genetic background, and summarize available therapeutic options. Diagnostic criteria for ALS-FTSD create distinct categories based on the type of neuropsychological manifestations, i.e., changes in behavior, impaired social cognition, executive dysfunction, and language or memory impairment. Cognitive impairment is found in up to 65%, while frank dementia affects about 15% of ALS patients. ALS motor and cognitive manifestations can worsen in parallel, becoming more pronounced when bulbar functions (affecting speech, swallowing, and salivation) are involved. Dementia can precede or develop after the appearance of motor symptoms. ALS-FTSD patients have a worse prognosis and shorter survival rates than patients with ALS or frontotemporal dementia alone. Important negative prognostic factors are behavioral and personality changes. From the clinician’s perspective, there are five major distinguishable ALS-FTSD subtypes: ALS with cognitive impairment, ALS with behavioral impairment, ALS with combined cognitive and behavioral impairment, fully developed frontotemporal dementia in combination with ALS, and comorbid ALS and Alzheimer’s disease. Although the most consistent ALS and ALS-FTSD pathology is a disturbance in transactive response DNA binding protein 43 kDa (TDP-43) metabolism, alterations in microtubule-associated tau protein metabolism have also been observed in ALS-FTSD. Early detection and careful monitoring of cognitive deficits in ALS are crucial for patient and caregiver support and enable personalized management of individual patient needs.

scholarly journals Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Tang ◽  
Yuan Yang ◽  
Zhenxiang Gong ◽  
Zehui Li ◽  
Lifang Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Uric Acid ◽  
Cognitive Impairment ◽  
Education Level ◽  
Older Age ◽  
Multivariate Linear Regression Analysis ◽  
Behavioral Impairment ◽  
Plasma Uric Acid ◽  
Als Patients ◽  
Lateral Sclerosis

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p &lt; 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p &lt; 0.001), and higher education level (β = 0.424, p &lt; 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p &lt; 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p &lt; 0.001) and the testing set (rs = 0.666, p &lt; 0.001).Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

Plasma Creatinine Level Does Not Predict Respiratory Function in Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-5
Author(s):  
João Morgadinho ◽  
Ana Catarina Pronto-Laborinho ◽  
Vasco A. Conceição ◽  
Marta Gromicho ◽  
Susana Pinto ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Creatinine Level ◽  
Cox Regression ◽  
Functional Decline ◽  
Plasma Creatinine ◽  
Plasma Creatinine Level ◽  
Decline Rate ◽  
Respiratory Outcome ◽  
Als Patients ◽  
Lateral Sclerosis

In amyotrophic lateral sclerosis (ALS) lower plasma creatinine level has been associated with shorter survival and faster functional decline. It has not been clear if creatinine is associated with respiratory outcome. We analyzed retrospectively a population of unselected ALS patients. Multiple-regression and Cox-regression analyses were performed. We included 233 patients, mean age 62.8, mean disease duration of 18.6 months. At baseline, creatinine was significantly associated with ALSFRS-R, but not with its decline rate. No predictive value was disclosed for FVC, or their decline rate, or with survival. We did not confirm that creatinine is a marker of respiratory outcome.

Coping strategies among amyotrophic lateral sclerosis (ALS) patients: an integrative review

2021 ◽  
Author(s):  
Georgiana Soares Leandro ◽  
Mário Emílio Teixeira Dourado Júnior ◽  
Glauciane Costa Santana ◽  
Luan Samy Xavier Dantas
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Coping Strategies ◽  
Integrative Review ◽  
Als Patients ◽  
Lateral Sclerosis

scholarly journals Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James C. Dodge ◽  
Jinlong Yu ◽  
S. Pablo Sardi ◽  
Lamya S. Shihabuddin
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Cholesterol Homeostasis ◽  
Cholesterol Oxidation ◽  
Therapeutic Approaches ◽  
Cellular Survival ◽  
Sporadic Als ◽  
Human Motor ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractAberrant cholesterol homeostasis is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease that is due to motor neuron (MN) death. Cellular toxicity from excess cholesterol is averted when it is enzymatically oxidized to oxysterols and bile acids (BAs) to promote its removal. In contrast, the auto oxidation of excess cholesterol is often detrimental to cellular survival. Although oxidized metabolites of cholesterol are altered in the blood and CSF of ALS patients, it is unknown if increased cholesterol oxidation occurs in the SC during ALS, and if exposure to oxidized cholesterol metabolites affects human MN viability. Here, we show that in the SOD1G93A mouse model of ALS that several oxysterols, BAs and auto oxidized sterols are increased in the lumbar SC, plasma, and feces during disease. Similar changes in cholesterol oxidation were found in the cervical SC of sporadic ALS patients. Notably, auto-oxidized sterols, but not oxysterols and BAs, were toxic to iPSC derived human MNs. Thus, increased cholesterol oxidation is a manifestation of ALS and non-regulated sterol oxidation likely contributes to MN death. Developing therapeutic approaches to restore cholesterol homeostasis in the SC may lead to a treatment for ALS.

scholarly journals Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 11 (7) ◽  
pp. 906
Author(s):  
Nimeshan Geevasinga ◽  
Mehdi Van den Bos ◽  
Parvathi Menon ◽  
Steve Vucic
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Cortical Excitability ◽  
Muscular Atrophy ◽  
Close Relationship ◽  
Bulbar Onset ◽  
Als Patients ◽  
Transcranial Magnetic Simulation ◽  
Cortical Dysfunction ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.

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