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Psychologists have been applying neurorehabilitation models of care for many years. These practitioners come from different training backgrounds and use a variety of titles to refer to themselves despite considerable overlap in practice patterns, professional identification, and salary. Titles like 'neurorehabilitation psychologist' and 'rehabilitation neuropsychologist' are sometimes used by practitioners in the field to indicate their specialty area, but are not formally recognized by the American Psychological Association, the American Board of Professional Psychology, or by training councils in clinical neuropsychology (CN) or rehabilitation psychology (RP). Neither the CN or RP specialties alone fully address or define the competencies, skill sets, and clinical experiences required to provide high quality, comprehensive neurorehabilitation psychology services across settings. Therefore, irrespective of practice setting, we believe that both clinical neuropsychologists and rehabilitation psychologists should ideally have mastery of specific, overlapping competencies and a philosophical approach to care that we call neurorehabilitation psychology in this paper. Trainees and early career professionals who aspire to practice in this arena are often pressured to prioritize either CN or RP pathways over the other, with anxiety about perceived and real potential for falling short in their training goals. In the absence of an explicit training path or formal guidelines, these professionals emerge only after the opportunity, privilege, or frank luck of working with specific mentors or in exceptional patient care settings that lend themselves to obtaining integrated competencies in neurorehabilitation psychology. This paper reflects the efforts of 7 practitioners to preliminarily define the practice and philosophies of neurorehabilitation psychology, the skill sets and competencies deemed essential for best practice, and essential training pathway elements. We propose competencies designed to maximize the integrity of training and provide clear guideposts for professional development.
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Rehabilitación Neurológica , Humanos , Ansiedad , Mentores , Presión , Salarios y BeneficiosRESUMEN
OBJECTIVE: The objective of this study was to describe clinical features, [18 F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB). METHODS: This is a clinicopathologic case-control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA-DLBD. We analyzed clinical features and compared FDG-PET metabolism in LPA-DLBD to an independent group of patients with clinical pDLB and regional α-synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB-DLBD). RESULTS: All patients with LPA-DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA-DLBD, LPA-Alzheimer's disease (LPA-AD), and LPA-frontotemporal lobar degeneration (LPA-FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA-DLBD patients. Seventy-five percent of the patients with LPA-DLBD showed a parietal-dominant pattern of hy pometabolism; LPA-FTLD - temporal-dominant pattern, whereas LPA-AD showed heterogeneous patterns of hypometabolism. LPA-DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA-DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α-synuclein burden in the middle frontal and inferior parietal cortices compared to DLB-DLBD. INTERPRETATION: Whereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α-synuclein-associated functional impairment of the dominant parietal lobe. ANN NEUROL 2021;89:520-533.
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Enfermedad de Alzheimer/diagnóstico por imagen , Afasia Progresiva Primaria/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Afasia Progresiva Primaria/patología , Afasia Progresiva Primaria/fisiopatología , Femenino , Fluorodesoxiglucosa F18 , Degeneración Lobar Frontotemporal/diagnóstico por imagen , Degeneración Lobar Frontotemporal/patología , Degeneración Lobar Frontotemporal/fisiopatología , Humanos , Pruebas del Lenguaje , Enfermedad por Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/fisiopatología , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression. METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). RESULTS: Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. CONCLUSIONS: This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.
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Leucoencefalopatías , Enfermedades Neurodegenerativas , Sustancia Blanca , Encéfalo/patología , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/etiología , Leucoencefalopatías/terapia , Enfermedades Neurodegenerativas/patología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers.
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Cerebelo/metabolismo , Expansión de las Repeticiones de ADN , Proteínas/genética , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Proteína C9orf72 , Cerebelo/patología , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Estudios de Cohortes , Femenino , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/genética , Demencia Frontotemporal/metabolismo , Demencia Frontotemporal/patología , Heterocigoto , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/metabolismo , Corteza Motora/patología , Enfermedad de la Neurona Motora/complicaciones , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/metabolismo , Enfermedad de la Neurona Motora/patología , Biosíntesis de Proteínas , ARN Mensajero/metabolismoRESUMEN
Objective: To critically review contemporary theoretical models, diagnostic approaches, clinical features, and assessment findings in Functional Cognitive Disorder (FCD), and make recommendations for neuropsychological evaluation of this condition. Method: Narrative review. Results: FCD is common in neuropsychological practice. It is characterized by cognitive symptoms that are not better explained by another medical or psychiatric disorder. The cognitive symptoms are associated with distress and/or limitations in daily functioning, but are potentially reversible with appropriate identification and treatment. Historically, a variety of diagnostic frameworks have attempted to capture this condition. A contemporary conceptualization of FCD positions it as a subtype of Functional Neurological Disorder, with shared and unique etiological factors. Patients with FCD tend to perform normally on neuropsychological testing or demonstrate relatively weak memory acquisition (e.g. list learning trials) in comparison to strong attention and delayed recall performance. Careful history-taking and behavioral observations are essential to support the diagnosis of FCD. Areas of ongoing controversy include operationalizing "internal inconsistencies" and the role of performance validity testing. Evidence for targeted interventions remains scarce. Conclusions: Neuropsychologists familiar with FCD can uniquely contribute to the care of patients with this condition by improving diagnostic clarity, richening case formulation, communicating effectively with referrers, and leading clinical management. Further research is needed to refine diagnosis, prognosis, and treatment.
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Trastornos del Conocimiento , Disfunción Cognitiva , Humanos , Pruebas Neuropsicológicas , Trastornos del Conocimiento/diagnóstico , PronósticoRESUMEN
Numerous kindreds with familial frontotemporal dementia and/or amyotrophic lateral sclerosis have been linked to chromosome 9, and an expansion of the GGGGCC hexanucleotide repeat in the non-coding region of chromosome 9 open reading frame 72 has recently been identified as the pathogenic mechanism. We describe the key characteristics in the probands and their affected relatives who have been evaluated at Mayo Clinic Rochester or Mayo Clinic Florida in whom the hexanucleotide repeat expansion were found. Forty-three probands and 10 of their affected relatives with DNA available (total 53 subjects) were shown to carry the hexanucleotide repeat expansion. Thirty-six (84%) of the 43 probands had a familial disorder, whereas seven (16%) appeared to be sporadic. Among examined subjects from the 43 families (n = 63), the age of onset ranged from 33 to 72 years (median 52 years) and survival ranged from 1 to 17 years, with the age of onset <40 years in six (10%) and >60 in 19 (30%). Clinical diagnoses among examined subjects included behavioural variant frontotemporal dementia with or without parkinsonism (n = 30), amyotrophic lateral sclerosis (n = 18), frontotemporal dementia/amyotrophic lateral sclerosis with or without parkinsonism (n = 12), and other various syndromes (n = 3). Parkinsonism was present in 35% of examined subjects, all of whom had behavioural variant frontotemporal dementia or frontotemporal dementia/amyotrophic lateral sclerosis as the dominant clinical phenotype. No subject with a diagnosis of primary progressive aphasia was identified with this mutation. Incomplete penetrance was suggested in two kindreds, and the youngest generation had significantly earlier age of onset (>10 years) compared with the next oldest generation in 11 kindreds. Neuropsychological testing showed a profile of slowed processing speed, complex attention/executive dysfunction, and impairment in rapid word retrieval. Neuroimaging studies showed bilateral frontal abnormalities most consistently, with more variable degrees of parietal with or without temporal changes; no case had strikingly focal or asymmetric findings. Neuropathological examination of 14 patients revealed a range of transactive response DNA binding protein molecular weight 43 pathology (10 type A and four type B), as well as ubiquitin-positive cerebellar granular neuron inclusions in all but one case. Motor neuron degeneration was detected in nine patients, including five patients without ante-mortem signs of motor neuron disease. While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings.
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Esclerosis Amiotrófica Lateral/genética , Demencia Frontotemporal/genética , Proteínas/genética , Edad de Inicio , Anciano , Afasia Progresiva Primaria/genética , Afasia Progresiva Primaria/psicología , Proteína C9orf72 , Cromosomas Humanos Par 9/genética , Estudios de Cohortes , ADN/genética , Expansión de las Repeticiones de ADN/genética , Femenino , Florida/epidemiología , Heterocigoto , Humanos , Procesamiento de Imagen Asistido por Computador , Péptidos y Proteínas de Señalización Intercelular/genética , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Pruebas Neuropsicológicas , Enfermedad de Parkinson/genética , Tomografía de Emisión de Positrones , Progranulinas , Sistema de Registros , Tomografía Computarizada de Emisión de Fotón Único , Población Blanca , Proteínas tau/genéticaRESUMEN
Introduction: The neuropsychological profile of CSF1R-related leukoencephalopathy (CRL) is undefined. This study defines the profile, contrasts it with that of other dementia syndromes, and highlights measures sensitive to cognitive impairment. Methods: We administered a standardized battery of neuropsychological tests to five consecutive CRL cases. Results: The neuropsychological profile of CRL reflects impaired general cognitive function, processing speed, executive function, speeded visual problem solving, verbal fluency, and self-reported depression and anxiety. Confrontation naming and memory are preserved. Within cognitive domains, certain measures more frequently identified impairment than others. Discussion: CRL impairs general cognitive function, processing speed, executive function. Language and visual problem solving may be impaired if processing speed is required. Confrontation naming and memory are uniquely preserved, contrasting CRL to other dementia syndromes. Cognitive screens excluding processing speed and executive function may not detect CRL cognitive manifestations. Findings sharply define cognitive impairment of CRL and inform cognitive test selection.
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Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications, termed "long COVID". It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this "normal cognition" phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the "memory-speed impaired" neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder "dysexecutive" neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of long COVID, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.
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Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications. It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this "normal cognition" phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the "memory-speed impaired" neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder "dysexecutive" neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of COVID-19, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.
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Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.
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Pruebas Neuropsicológicas , Convulsiones , Humanos , Femenino , Persona de Mediana Edad , Convulsiones/terapia , Pruebas Neuropsicológicas/normas , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Disfunción Cognitiva/fisiopatología , Trastornos Psicofisiológicos/terapia , ElectroencefalografíaRESUMEN
The range of behavioral changes occurring after stroke has not yet been fully characterized. To evaluate behavioral symptoms after stroke and clinical characteristics that may influence the number and frequency of such symptoms, we compared 53 survivors of mild ischemic stroke with 30 stroke-free controls. Stroke survivor and control participants completed self-ratings of behavioral symptoms and were administered measures of cognitive status (ie, Beck Depression Inventory II, Mini-Mental State Examination, and Controlled Oral Word Association Test). Informants of stroke survivors and controls completed ratings of behavioral symptoms and functional status (ie, Neuropsychiatric Inventory Questionnaire, Informant Questionnaire on Cognitive Decline in the Elderly, and Functional Activities Questionnaire). More behavioral symptoms were observed in stroke survivors than in controls (mean [standard deviation] total number of symptoms on the Neuropsychiatric Inventory Questionnaire, 2.1 [2.0] vs 1.1 [1.5]; P = .02). Informants of stroke survivors were more likely to recognize behavioral symptoms than were stroke survivors themselves. Higher initial stroke severity was associated with more behavioral symptoms. With more behavioral symptoms, there was more functional impairment. Our findings suggest that behavioral symptoms can have unique and troublesome effects on stroke patients. Future research is needed to understand how the identification of behavioral symptoms after stroke can improve care in stroke survivors.
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Isquemia Encefálica/psicología , Depresión/psicología , Accidente Cerebrovascular/psicología , Sobrevivientes/psicología , Actividades Cotidianas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Cognición , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Patients with aneurysmal subarachnoid hemorrhage (aSAH) often sustain substantial cognitive and functional impairment. Traditional outcome measures have emphasized radiographic and gross clinical outcomes, but cognitive and functional outcomes are less frequently documented. This pilot study assessed the feasibility of administering longitudinal cognitive and neuropsychological testing and tracked patterns of functional improvement in aSAH patients. PATIENTS AND METHODS: Standardized cognitive and neuropsychological testing were administered to a prospective cohort of aSAH patients admitted for treatment to our tertiary care center. Thirty consecutive aSAH patients (Hunt and Hess score 1-3) were enrolled over 23-months and baseline evaluations were completed within 24-h after admission. Patients were followed prospectively after treatment (coiling or clipping) at 1-, 3-, 6-, and 12-months. Functional outcome measures included the Montreal Cognitive Assessment, the Neuropsychiatric Inventory-Questionnaire, and the Functional Activities Questionnaire. RESULTS: Of the 30 patients, 23 (77%) followed-up at 3-months, 21 (70%) at 6-months, and 19 (63%) at 12-months. Improvement from baseline to follow-up at 12-months was noted for general cognitive function (pâ¯=â¯.004), memory (pâ¯=â¯.025), and executive function (pâ¯=â¯.039), with the greatest improvement occurring within 6-months. Daily function also improved mostly within 6-months (pâ¯=â¯.022) while changes in neuropsychological disturbances were insignificant from baseline to follow-up at 12-months (pâ¯=â¯.216). CONCLUSION: Standardized cognitive and neuropsychological testing provides metrics for evaluating functional outcomes following treatment of aSAH. The addition of a brief battery of tests to routine clinical and radiographic evaluations is feasible. The main limitations are related to practice and referral patterns, and future studies are needed to evaluate the impact of treatment modalities on functional outcomes.
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Hemorragia Subaracnoidea/psicología , Hemorragia Subaracnoidea/cirugía , Actividades Cotidianas , Adulto , Anciano , Cognición , Estudios de Cohortes , Función Ejecutiva , Estudios de Factibilidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Memoria , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Proyectos Piloto , Estudios Prospectivos , Recuperación de la Función , Resultado del TratamientoRESUMEN
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.
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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/fisiopatología , Humanos , Pruebas NeuropsicológicasRESUMEN
There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a G4C2 repeat expansion in the C9ORF72 gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. G4C2 repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in C9ORF72-associated ALS (c9ALS). Therapeutics that target G4C2 RNA, such as antisense oligonucleotides (ASOs) and small molecules, are thus being actively investigated. A limitation in moving such treatments from bench to bedside is a lack of pharmacodynamic markers for use in clinical trials. We explored whether poly(GP) proteins translated from G4C2 RNA could serve such a purpose. Poly(GP) proteins were detected in cerebrospinal fluid (CSF) and in peripheral blood mononuclear cells from c9ALS patients and, notably, from asymptomatic C9ORF72 mutation carriers. Moreover, CSF poly(GP) proteins remained relatively constant over time, boding well for their use in gauging biochemical responses to potential treatments. Treating c9ALS patient cells or a mouse model of c9ALS with ASOs that target G4C2 RNA resulted in decreased intracellular and extracellular poly(GP) proteins. This decrease paralleled reductions in G4C2 RNA and downstream G4C2 RNA-mediated events. These findings indicate that tracking poly(GP) proteins in CSF could provide a means to assess target engagement of G4C2 RNA-based therapies in symptomatic C9ORF72 repeat expansion carriers and presymptomatic individuals who are expected to benefit from early therapeutic intervention.
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Esclerosis Amiotrófica Lateral/genética , Biomarcadores/metabolismo , Proteína C9orf72/genética , Repeticiones de Dinucleótido/genética , Adulto , Anciano , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/patología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Línea Celular , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Estudios Longitudinales , Ratones , Persona de Mediana Edad , Neuronas/metabolismo , Oligonucleótidos Antisentido/farmacología , Pronóstico , ARN/genéticaRESUMEN
Age-related deficits in context processing were examined in relationship to two predominant theories of cognitive aging (the Inhibitory Deficit and Processing Speed Models). Older and younger adults completed a measure of context processing (AX Continuous Performance Test (CPT) task) as well as a computerized battery of inhibitory tasks: Stroop, garden path sentences, go no-go, and the stop-signal paradigm. Participants also completed a simple processing speed task. After controlling for baseline differences in processing speed, age effects were detected on the AX-CPT. Smaller, but significant age effects were noted on the Stroop and stop-signal tasks, but no significant age effects were found on the garden path sentence and go no-go tasks. Intertask correlations were weak, providing little evidence for a homogenous or uniform construct of inhibition. The sensitivity of the AX-CPT to cognitive aging is discussed in the context of existing theories of cognitive aging. The authors suggest that deficits in context processing and utilization may underlie cognitive aging phenomena.
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Envejecimiento/fisiología , Cognición/fisiología , Área de Dependencia-Independencia , Inhibición Psicológica , Percepción Visual/fisiología , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Solución de Problemas/fisiología , Tiempo de Reacción/fisiología , Estadística como AsuntoRESUMEN
OBJECTIVE: Confrontation naming is commonly assessed in neuropsychological practice, but few standardized measures of naming exist and those that do are susceptible to the effects of education and culture. The Neuropsychological Assessment Battery (NAB) Naming Test is a 31-item measure used to assess confrontation naming. Despite adequate psychometric information provided by the test publisher, there has been limited independent validation of the test. METHOD: In this study, we investigated the convergent and discriminant validity, internal consistency, and alternate forms reliability of the NAB Naming Test in a sample of adults (Form 1: n = 247, Form 2: n = 151) clinically referred for neuropsychological evaluation. RESULTS: Results indicate adequate-to-good internal consistency and alternate forms reliability. We also found strong convergent validity as demonstrated by relationships with other neurocognitive measures. We found preliminary evidence that the NAB Naming Test demonstrates a more pronounced ceiling effect than other commonly used measures of naming. CONCLUSIONS: To our knowledge, this represents the largest published independent validation study of the NAB Naming Test in a clinical sample. Our findings suggest that the NAB Naming Test demonstrates adequate validity and reliability and merits consideration in the test arsenal of clinical neuropsychologists.
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Pruebas Neuropsicológicas/normas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cognición , Análisis Discriminante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Desempeño Psicomotor , Reproducibilidad de los Resultados , Prueba de Secuencia Alfanumérica , Adulto JovenRESUMEN
Declines in the ability to process context information may represent a fundamental mechanism of age-related cognitive changes. Two components of context processing--activation/updating and maintenance--were examined in a sample of healthy younger and older adults, along with individuals suffering from early stage dementia of the Alzheimer's type (DAT). All older adult groups showed context activation/updating impairments, whereas context maintenance was only impaired in the oldest adults (age>75 years) and was further exacerbated in DAT individuals. The results suggest that context processing may be composed of functionally dissociable components and point to the utility of this construct in understanding the timecourse of cognitive decline in healthy and pathological aging.
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Envejecimiento/fisiología , Enfermedad de Alzheimer/diagnóstico , Cognición/fisiología , Estado de Salud , Procesos Mentales , Semántica , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Pruebas Neuropsicológicas , Tiempo de Reacción , Índice de Severidad de la EnfermedadRESUMEN
The Boston Naming Test is one of the most widely used neuropsychological instruments; yet, there has been limited use of modern psychometric methods to investigate its properties at the item level. The current study used Item response theory to examine each item's difficulty and discrimination properties, as well as the test's measurement precision across the range of naming ability. Participants included 300 consecutive referrals to the outpatient neuropsychology service at Mayo Clinic in Florida. Results showed that successive items do not necessarily reflect a monotonic increase in psychometric difficulty, some items are inadequate to distinguish individuals at various levels of naming ability, multiple items provide redundant psychometric information, and measurement precision is greatest for persons within a low-average range of ability. These findings may be used to develop short forms, improve reliability in future test versions by replacing psychometrically poor items, and analyze profiles of intra-individual variability.
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Trastornos del Conocimiento/diagnóstico , Discriminación en Psicología/fisiología , Nombres , Pruebas Neuropsicológicas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Pacientes Ambulatorios , Psicometría , Valores de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
OBJECTIVE: To identify patient features associated with early and late depression after traumatic brain injury (TBI). PARTICIPANTS: 3 clinical trauma groups (mild TBI, moderate-severe TBI, orthopedic injury) and their significant others. MEASURES: Preinjury: age, education, substance abuse, and psychiatric history; Injury severity: classification using Glasgow Coma Scale and cranial CT scan, posttraumatic amnesia; Early impairment: Neurobehavioral Functioning Inventory (NFI), Impaired Self-Awareness (ISA); Social and family support: Multidimensional Scale of Perceived Social Support, Family Assessment Device; Depression: NFI Depression Scale. METHOD: Regression analyses of predictor variables on early and late measures of depression. RESULTS: Depression rates did not differ among the 3 trauma groups. Preinjury level of education, previous psychiatric history, and perceived level of social support explained a small portion of the variance in depressive symptoms. Patients' self-assessment of their impairment at discharge was most strongly correlated with both early and late depression. ISA was associated with reduced self-report of depressive symptoms. However, when those with ISA were excluded from the analysis, self-assessment of impairment remained strongly associated with depression. CONCLUSIONS: Patients' self-assessment of impairment is strongly associated with early and late depression. Presence and severity of TBI does not appear to play a direct role in depression but does appear related to ISA, which serves as a barrier to the development of depression. Focusing on impairment appears to be a cardinal feature of depression in both patients with TBI and an orthopedic trauma group.