RESUMEN
Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature.
Asunto(s)
Trastornos del Conocimiento/etiología , Demencia Frontotemporal/complicaciones , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación/genética , Adulto , Anciano , Atención , Análisis Mutacional de ADN , Femenino , Demencia Frontotemporal/genética , Humanos , Lenguaje , Masculino , Memoria , Persona de Mediana Edad , Pruebas Neuropsicológicas , Progranulinas , Curva ROC , Estadísticas no Paramétricas , Aprendizaje VerbalRESUMEN
OBJECTIVE: To examine the tolerability and estimate the treatment effect of cognitive-behavioral therapy (CBT) delivered soon after mild traumatic brain injury to patients at risk for chronic postconcussion syndrome (PCS). SETTING: Tertiary rehabilitation center. PARTICIPANTS: Twenty-eight patients with uncomplicated mild traumatic brain injury, determined to be at risk for chronic PCS based on a published algorithm that incorporates subacute postconcussion symptoms and maladaptive illness beliefs (recovery expectations and perceived consequences). They were enrolled within 6 weeks postinjury. DESIGN: Open-label, parallel-group, randomized controlled trial, with masked outcome assessment 3 months after enrolment. Interventions were (1) treatment as usual (education, reassurance, and symptom management strategies) from an occupational therapist, or (2) treatment as usual plus CBT delivered by a psychologist. MAIN MEASURES: Rivermead Postconcussion Symptoms Questionnaire. RESULTS: Four participants (2:2) withdrew. Treatment credibility and satisfaction ratings were high in the CBT group. Treatment effect sizes were moderate for postconcussion symptoms (Cohen d = 0.74) and moderate-large for most secondary outcome measures (Cohen d = 0.62-1.61). Fewer participants receiving CBT had a diagnosis of PCS at follow-up (54% vs 91%, P < .05). CONCLUSION: Our preliminary data suggest that CBT delivered soon after mild traumatic brain injury is well tolerated and may facilitate recovery in patients who are at risk for chronic PCS. A definitive clinical trial is warranted.
Asunto(s)
Lesiones Encefálicas/terapia , Terapia Cognitivo-Conductual/métodos , Síndrome Posconmocional/patología , Adulto , Lesiones Encefálicas/diagnóstico , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proyectos Piloto , Síndrome Posconmocional/terapia , Valor Predictivo de las Pruebas , Prevención Primaria/métodos , Recuperación de la Función/fisiología , Valores de Referencia , Centros de Rehabilitación , Medición de Riesgo , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The regional distribution of degeneration of the corpus callosum (CC) in dementia is not yet clear. This study compared regional CC size in participants (n = 179) from the Cache County Memory and Aging Study. Participants represented a range of cognitive function: Alzheimer's disease (AD), vascular dementia (VaD), mild ambiguous (MA-cognitive problems, but not severe enough for diagnosis of dementia), and healthy older adults. CC outlines obtained from midsagittal magnetic resonance images were divided into 99 equally spaced widths. Factor analysis of these callosal widths identified 10 callosal regions. Multivariate analysis of variance revealed significant group differences for anterior and posterior callosal regions. Post-hoc pairwise comparisons of CC regions in patient groups as compared to the control group (controlling for age) revealed trends toward smaller anterior and posterior regions, but not all were statistically significant. As compared to controls, significantly smaller anterior and posterior CC regions were found in the AD group; significantly smaller anterior CC regions in the VaD group; but no significant CC regional differences in the MA group. Findings suggest that dementia-related CC atrophy occurs primarily in the anterior and posterior portions.
Asunto(s)
Enfermedad de Alzheimer/patología , Cuerpo Calloso/patología , Demencia Vascular/patología , Anciano , Anciano de 80 o más Años , Atrofia , Femenino , Evaluación Geriátrica , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Características de la ResidenciaRESUMEN
Previous investigations have reported decreased size of the corpus callosum (CC) in autism. However, little is known of the regional distribution of these callosal abnormalities. Additional uncertainty exists regarding the role of head size with respect to variations in callosal size in individuals with autism. This study investigated the size of the CC in 5 groups of high functioning individuals: (1) normocephalic autistic individuals; (2) autism with macrocephaly; (3) non-autistic normocephalic controls; (4) non-autistic participants with benign macrocephaly; and (5) a reading disordered (RD) group, comprised of non-autistic individuals with a deficit in reading. The CC was traced from midsaggital MRIs and the outlines partitioned into 99 equidistant width measures. Factor analysis of the 99 widths revealed 10 contiguous callosal regions. Individuals with macrocephaly (autistic and non-autistic) had larger total CC size. Regional analysis revealed a significantly larger CC midbody in macrocephaly, regardless of presence or absence of autism. Within normocephalic individuals, those with autism had a smaller CC genu and midbody than either non-autistic controls or RD individuals. These results underscore the importance of considering head size in studies of CC morphology in autism. These findings add to the literature implicating problems of interhemispheric connectivity being present in individuals with autism.
Asunto(s)
Agenesia del Cuerpo Calloso , Trastorno Autístico/diagnóstico , Encéfalo/anomalías , Encéfalo/patología , Cuerpo Calloso/patología , Anomalías Craneofaciales/diagnóstico , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Adolescente , Adulto , Trastorno Autístico/fisiopatología , Cefalometría , Niño , Anomalías Craneofaciales/fisiopatología , Dislexia/diagnóstico , Dislexia/fisiopatología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Valores de ReferenciaRESUMEN
BACKGROUND: Misrecognition of symptoms in the early stages of frontotemporal dementia (FTD) frequently contributes to diagnostic delay. Three frameworks have been proposed for the clinical identification of prodromal FTD: (1) cognitive profiling, (2) the presence of behavioral/psychiatric symptoms in the absence of memory complaints, and (3) a combined approach of cognitive, behavioral, and neuroimaging features. OBJECTIVE: To evaluate current conceptual frameworks for the clinical recognition of prodromal FTD with current empirical evidence. METHOD: We performed a comprehensive PsychINFO and MEDLINE database search to identify articles investigating the prodromal symptoms of FTD. CONCLUSIONS: The 3 frameworks capture important aspects of the clinical picture of prodromal FTD but require further refinement. The prodromal stage of FTD is characterized by both cognitive and behavioral features. Diagnostic accuracy will likely be improved by considering a combination of cognitive and behavioral features, because some features overlap with prodromes for Alzheimer's disease and vascular dementia.
Asunto(s)
Demencia/diagnóstico , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Demencia/psicología , Diagnóstico Diferencial , Diagnóstico Precoz , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/psicología , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Mental flexibility is required to track and systematically alternate between 2 response sets. In this study, 719 individuals, 20 to 89 years old, engaged in 3 different tasks that required verbal and nonverbal cognitive switching. Of importance, each task allowed for independent measurement of component skills that are embedded in the higher level tasks. When gender, education, Full Scale IQ, and component skills were partialed out by multiple regression analyses, significant age effects were revealed for each task. This study provides evidence that executive functions--and verbal and nonverbal cognitive switching in particular--are affected by age independently from age-related changes in component skills. The results are discussed in terms of theories of executive control and neurologic correlates across the adult life span.