RESUMO
Amyotrophic lateral sclerosis (ALS) patients often express cognitive and behavioral dysfunctions within the so-called "frontotemporal spectrum disorders." Guidelines recommend screening of such dysfunctions, albeit only ALS dedicated tools are eventually suitable, due to the profound motor limitations induced by the disease. ALS Cognitive Behavioral Screen (ALS-CBS) is such a screening tool but normative data are not available, limiting its widespread implementation. Our aim consisted in producing normative data for the Italian version of the ALS-CBS. The scale was administered to n = 458 healthy controls with different age and education. Following translation and back translation of the original version of the test, normative data and correction scores for the ALS-CBS cognitive subtest (ALS-CBSci) were generated. Furthermore, n = 100 ALS consecutive outpatients with a wide range of cognitive and motor severity underwent to the ALS-CBS, besides FAB and Weigl sorting test (WST), in order to check its usability. Completion rate was 100% for ALS-CBS and WST, and 68% for the FAB. Corrected ALS-CBS scores showed 12% detection rate of significant cognitive dysfunction with a moderate kappa with FAB and WST. For the ALS-CBS behavioral subtest (ALS-CBSbi), a caregiver was available for n = 81 ALS patients and asked to complete the subset. The detection rate for behavioral dysfunction was 55.5%, and a mild correlation between with the Caregiver Burden Inventory was present (r = - 0.26, p = 0.04). In conclusion, we offer here normative data for the ALS-CBS, a handy tool for screening frontotemporal spectrum dysfunctions in ALS patients, and confirm its usability and validity in an outpatient setting.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Sintomas Comportamentais/diagnóstico , Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Sintomas Comportamentais/etiologia , Disfunção Cognitiva/etiologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
The clinical neuropsychologist has the opportunity to be uniquely involved in the evaluation and treatment of individuals with amyotrophic lateral sclerosis (ALS). We review the current literature that defines cognitive and behavioral symptoms in ALS, including current knowledge of the neuropathological and genetic underpinning for these symptoms. There are unique considerations for clinical neuropsychological evaluation and clinical research in ALS and we highlight these in this review. Specifically, we shed light on special factors that contribute to our understanding of cognitive and behavioral impairment in ALS, including co-morbid symptoms, differential diagnosis, and considerations for longitudinal tracking of phenotypes. We discuss the rationale for proposing a specific approach to such as cognitive screening, test selection, response modality consideration, and test-retest intervals. With this didactic overview, the clinical neuropsychologist has the potential to learn more about the heterogeneous presentation of motor and neuropsychological symptoms in ALS. Furthermore, the reader has the opportunity to understand what it takes to develop a valid assessment approach particularly when the phenotype of ALS remains undefined in some regards. This clinical practice review sets the stage for the clinical neuropsychologist to further contribute to our clinical and scientific understanding of ALS and cognition.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/psicologia , Esclerose Lateral Amiotrófica/fisiopatologia , Humanos , Testes NeuropsicológicosRESUMO
Cognitive decline (CD) is common but often under-recognized in ALS due to the scarcity of adequate cognitive screening methods. In this scenario, the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) is the most investigated instrument and presents high sensitivity to identify CD. Currently, there are no validated cognitive screening tools for ALS patients in the Brazilian population and little is known about the frequency of ALS related CD in the country. We assessed the accuracy of the Brazilian Portuguese version of ALS-CBS Cognitive Section (ALS-CBS-Br) for classifying the cognitive status of Brazilian patients compared to a standard neuropsychological battery, and estimated the prevalence of CD in the Brazilian ALS population. Among 73 initially recruited ALS patients, 49 were included. Twenty-four patients were excluded due to severe motor disability, FTD diagnosis or non-acceptance. Ten healthy controls were also included. Ten ALS patients (20%) were diagnosed with executive dysfunction (ALSci) based on the battery results. ALS-CBS-Br scores were significantly lower in the ALSci group (p < 0.001). The scale accuracy in detecting executive dysfunction was 0.906. Optimal cut-off score was 10/20 (specificity 0.872 and sensitivity 0.900). In conclusion, the ALS-CBS-Br may facilitate the recognition of CD in routine clinical care and complement future studies in our population.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/epidemiologia , Transtornos Cognitivos , Cultura , Idoso , Esclerose Lateral Amiotrófica/genética , Brasil/epidemiologia , Proteína C9orf72 , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Proteínas/genética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Caregivers of patients affected by amyotrophic lateral sclerosis (ALS) are involved with great determination in the treatment process since the earliest stages of the disease with an increasing burden to be of help to the ailing persons. AIM: To test separately the impact of ALS patients' cognitive and behavioural impairments on caregiver burden and mood status in 84 outpatient/main caregiver couples. DESIGN: Patients were tested with the ALS-Cognitive Behavioural Screen (ALSCBS-ci and -bi), Frontal Assessment Battery, Weigl's Sorting Test, Mini-Mental State Examination, Beck's Depression Inventory (BDI). Analogously, caregivers completed the BDI and Caregiver Burden Inventory (CBI). RESULTS: CBI correlated with ALSCBS-bi, besides ALSFRS-R, disease progression index and caregiver BDI. Caregiver BDI also correlated with ALSCBS-bi scores. No correlations were found with cognitive tests. The correlation between CBI and the ALSCBS-bi score was specifically sustained by the social burden sub-domain of CBI. CONCLUSIONS: As previously reported using other tools, behavioural impairment is a determinant of burden and mood in ALS caregivers. Conversely, cognitive impairment fails to emerge as a major target when aiming at easing the increasing burden or improving mood in ALS caregivers.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/psicologia , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Adulto , Afeto , Idoso , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida/psicologiaRESUMO
BACKGROUND: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. OBJECTIVE: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. METHODS: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). RESULTS: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. CONCLUSIONS: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.
Assuntos
Esclerose Lateral Amiotrófica/psicologia , Função Executiva , Idioma , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/fisiopatologia , Análise Discriminante , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Psicometria , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Lobo Temporal/fisiopatologiaRESUMO
Although amyotrophic lateral sclerosis (ALS) is classically considered a disorder exclusively affecting motor neurons, there is substantial clinical, neuroimaging, and neuropathologic evidence that more than half of patients have an associated syndrome of frontotemporal dysfunction. These syndromes range from frontotemporal dementia to behavioral or cognitive syndromes. Neuroimaging and neuropathologic findings are consistent with frontotemporal lobar degeneration that underpins alterations in network connectivity. Future clinical trials need to be stratified based on the presence or absence of frontotemporal dysfunction on the disease course of ALS.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/patologia , Transtornos Cognitivos/etiologia , Demência Frontotemporal/etiologia , Degeneração Lobar Frontotemporal/etiologia , Esclerose Lateral Amiotrófica/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Humanos , Transtornos da Linguagem/etiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Proteínas tau/genéticaRESUMO
The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.
Assuntos
Córtex Cerebral/patologia , Disfunção Cognitiva/patologia , Hipocampo/patologia , Lobo Parietal/patologia , Lobo Temporal/patologia , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Biomarcadores/análise , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Imagem de Tensor de Difusão , Feminino , Hipocampo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Lobo Parietal/fisiopatologia , Sensibilidade e Especificidade , Lobo Temporal/fisiopatologiaRESUMO
Mutations in the gene for superoxide dismutase type 1 cause amyotrophic lateral sclerosis (ALS), but are not thought to be associated with frontotemporal dementia (FTD). A lack of detailed case reports is one reason, among others, for this skepticism. This case report comments on a patient with familial ALS caused by I113T mutation in the SOD1 gene presenting with progressive cognitive and behavioral decline two years before developing progressive motor degeneration. In conclusion, this case provides evidence that SOD1 mutations can be associated with FTD.
Assuntos
Esclerose Lateral Amiotrófica/genética , Demência Frontotemporal/genética , Mutação/genética , Superóxido Dismutase/genética , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/complicações , Demência Frontotemporal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase-1RESUMO
Whether longitudinal diffusion tensor MRI imaging (DTI) can capture disease progression in patients with amyotrophic lateral sclerosis (ALS) is unclear. The primary goal of this study was to determine if DTI detects progression of the corticospinal tracts (CST) degeneration in ALS. Seventeen ALS patients and 19 age- and gender-matched healthy controls were scanned with DTI at baseline for cross-sectional analyses. For longitudinal analyses, the ALS patients had repeat DTI scans after eight months. Tractography of the CST was used to guide regions-of-interest (ROI) analysis and complemented by a voxelwise analysis. Cross-sectional study found that baseline FA of the right superior CST was markedly reduced in ALS patients compared to controls. The FA reductions in this region correlated with the disease severity in ALS patients. Longitudinal study found that FA change rate of the right superior CST significantly declined over time. In conclusion, longitudinal DTI study captures progression of upper motor fiber degeneration in ALS. DTI can be useful for monitoring ALS progression and efficacy of treatment interventions.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/fisiopatologia , Imagem de Tensor de Difusão/métodos , Degeneração Neural/patologia , Fibras Nervosas Mielinizadas/patologia , Idoso , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Degeneração Neural/fisiopatologia , Tratos Piramidais/patologiaRESUMO
Our objective was to determine whether apathy in amyotrophic lateral sclerosis (ALS) relates to structural changes associated with the degenerative process or disease related factors such as illness duration, physical disability, or hypoxia. Using diffusion tensor imaging (DTI) with fractional anisotropy (FA), we conducted a voxel-based analysis of whole-brain changes to investigate decline in white matter integrity as it correlates with apathy in ALS. Twenty-four patients enrolled in the study were compared with 24 age- and gender-matched controls. The relationship between FA and apathy scores was tested using a general linear model accounting for age, gender and functional disability in 16 ALS patients. Results showed that, using a spatially unbiased voxel-wise approach and the statistical map-driven region of interest (ROI), a significant negative correlation existed between FA and apathy change scores in the right anterior cingulum region, whereas ALS disease severity was significantly correlated with FA alterations in bilateral motor areas. Apathy was not correlated with clinical depression, disease duration or respiratory dysfunction. In conclusion, our findings point towards a biological basis for apathy in the anterior cingulum, consistent with research on apathy in other neurological populations.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/psicologia , Apatia , Encéfalo/patologia , Imagem de Tensor de Difusão , Adulto , Idoso , Anisotropia , Depressão/patologia , Imagem de Tensor de Difusão/instrumentação , Dominância Cerebral , Feminino , Giro do Cíngulo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/patologia , Tamanho da Amostra , Índice de Gravidade de DoençaRESUMO
Up to half of patients with ALS develop cognitive impairment during the course of the illness. Despite this, there is no simple tool for screening patients in the clinical setting. This study examines the sensitivity, specificity and accuracy of the ALS Cognitive Behavioral Screen (ALS-CBS). We administered the measure to 112 ALS patients, including 31 who also underwent comprehensive neuropsychological testing. Screen results were validated by determining the accuracy against the full battery. Optimal cut-off scores for predicting the correct diagnosis were determined, and mean scores were compared between patients, controls and different diagnostic groups. The results demonstrated that mean cognitive scores differed between ALS and normal controls (p < 0.0001). The cognitive section differentiated ALS-FTD from other ALS patients with 100% accuracy. Cognitively normal ALS patients could be distinguished from those with any cognitive deficit with 71% specificity and 85% sensitivity. A separate behavioral score was significantly lower in the ALS cohort compared to controls (p < 0.0001) and predicted ALS-FTD with 80% sensitivity and 88% specificity. In conclusion, the ALS-CBS can aid in detecting cognitive and behavioral impairment in a clinical setting, although it does not replace formal diagnostic assessment. Further validation with larger sample sizes will clarify its clinical utility.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Comportamento/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Demência Frontotemporal/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção/fisiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Aprendizagem Verbal/fisiologia , Adulto JovemRESUMO
UNLABELLED: Although impaired insight is a core diagnostic criterion for establishing the diagnosis of frontotemporal dementia (FTD), insight has rarely been studied in amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine differences between patient and informant (caregiver) reports of behavior and behavioral change in amyotrophic lateral sclerosis. METHODS: Behavioral data for 17 patients with ALS and 4 patients with ALS-FTD were analyzed. Behavioral changes were evaluated using the Frontal Systems Behavior Scale (FrSBe). We compared premorbid to current behavioral profiles and patient self-reports with those of their informants to determine the level of awareness regarding behavioral changes since the onset of ALS. RESULTS: ALS patients without FTD had normal insight, as defined by this study, although self-reports suggested mild behavioral abnormalities. In contrast, patients with ALS-FTD revealed a marked loss of insight regarding profound changes in behavior. CONCLUSIONS: Patients with ALS-FTD exhibit a profound lack of insight, which is not found in non-demented ALS patients. Patients without dementia have normal insight, although they report mild behavioral changes that might reflect a psychological response to the disease.
Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/psicologia , Demência Frontotemporal/fisiopatologia , Demência Frontotemporal/psicologia , Comportamento Social , Sintomas Afetivos , Esclerose Lateral Amiotrófica/complicações , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Estudos de Coortes , Função Executiva , Feminino , Demência Frontotemporal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Cognitive impairment in amyotrophic lateral sclerosis (ALS) is correlated with pathologic and radiographic changes in cerebral cortex beyond the motor regions. Clinically, evidence of impairment can be detected in up to 50 percent of patients through direct neuropsychological testing, although frank frontotemporal dementia (FTD) occurs in a limited percentage. Behavioral changes are also common and can be characterized primarily by the presence of increased apathy. Determining the underlying causes of cognitive or behavioral change may be confounded by several disease-related factors, including fatigue, respiratory compromise, depression, and treatment with medications such as riluzole. Studies assessing the evolution and relative risk for cognitive and behavioral impairment in ALS suggest at least two types of patients: those who have clear FTD in whom cognitive decline develops gradually and those who have mild cognitive or behavioral impairments in whom progression either does not occur or is difficult to detect. Limited data suggest that cognition and behavior influence compliance, management, and survival, although this requires further assessment.