RESUMO
Despite providing care for patients with "disturbances of the same organ," the brain, the therapeutic approaches used by neurologists and psychiatrists are, to some extent, distinct. With recognition of the closely coupled relationship between physical health and mental health, there is increased awareness of the need to provide an integrated, neuropsychiatric approach to the care of patients in neurology. In this review article, we provide a broad overview of how neurologists can use psychotherapeutic principles to enhance patient-physician interactions in the neurological setting (e.g., developing a therapeutic alliance; frame/boundary setting; active, empathic listening; acknowledging affect). These practices relate to a broad range of conditions, including, but not necessarily limited to epilepsy, traumatic brain injury, and functional neurological (conversion) disorder. The authors provide practical approaches that a neurologist can learn to leverage psychotherapeutic tools to enhance clinical encounters.
Assuntos
Transtorno Conversivo , Epilepsia , Neurologia , Encéfalo , Humanos , NeurologistasRESUMO
BACKGROUND AND OBJECTIVES: Vascular disease is a known risk factor for Alzheimer's disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF). METHODS: Subjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0-16), L-arginine (weeks 4-16), and tetrahydrobiopterin (weeks 8-16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition. RESULTS: A total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF. CONCLUSIONS: Treatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement. TRIAL REGISTRATION: This study is registered in https://www. CLINICALTRIALS: gov ; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.
Assuntos
Doença de Alzheimer , Inibidores de Hidroximetilglutaril-CoA Redutases , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Arginina/farmacologia , Arginina/uso terapêutico , Biopterinas/análogos & derivados , Circulação Cerebrovascular , Cognição , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Testes Neuropsicológicos , Óxido Nítrico Sintase Tipo III/farmacologia , Óxido Nítrico Sintase Tipo III/uso terapêutico , Estudo de Prova de Conceito , Sinvastatina/farmacologia , Sinvastatina/uso terapêuticoRESUMO
We analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the women's scores dropped 1.6 times more than the men's did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men.
Assuntos
Doença de Alzheimer/psicologia , Transtornos da Memória/psicologia , Memória/fisiologia , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Caracteres Sexuais , Aprendizagem VerbalRESUMO
Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency event-related potential (ERP) component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage AD. Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using principal components analysis. C145 amplitudes and spatial distributions were compared among controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals.
Assuntos
Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Testes Neuropsicológicos , Tempo de Reação/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Encéfalo/fisiologia , Cognição/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Análise de Componente Principal/métodosRESUMO
This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer's disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Potenciais Evocados/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Disfunção Cognitiva/patologia , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Potenciais Evocados/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Nootrópicos/farmacologia , Nootrópicos/uso terapêutico , Resultado do TratamentoRESUMO
Predicting which individuals will progress to Alzheimer's disease (AD) is important in both clinical and research settings. We used brain Event-Related Potentials (ERPs) obtained in a perceptual/cognitive paradigm with various processing demands to predict which individual Mild Cognitive Impairment (MCI) subjects will develop AD versus which will not. ERP components, including P3, memory "storage" component, and other earlier and later components, were identified and measured by Principal Components Analysis. When measured for particular task conditions, a weighted set of eight ERP component_conditions performed well in discriminant analysis at predicting later AD progression with good accuracy, sensitivity, and specificity. The predictions for most individuals (79%) had high posterior probabilities and were accurate (88%). This method, supported by a cross-validation where the prediction accuracy was 70-78%, features the posterior probability for each individual as a method of determining the likelihood of progression to AD. Empirically obtained prediction accuracies rose to 94% when the computed posterior probabilities for individuals were 0.90 or higher (which was found for 40% of our MCI sample).
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Encéfalo/patologia , Potenciais Evocados/fisiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/fisiopatologia , Análise Discriminante , Progressão da Doença , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Análise de Componente Principal , Reprodutibilidade dos TestesRESUMO
Behavioral markers measured through neuropsychological testing in mild cognitive impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimer's disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (principal component analysis, PCA), and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the participants (81%) were in the highly confident probability bins (.70-1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling.
Assuntos
Doença de Alzheimer/psicologia , Transtornos Cognitivos/psicologia , Testes Neuropsicológicos , Idoso , Depressão/diagnóstico , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Progressão da Doença , Escolaridade , Feminino , Humanos , Masculino , Memória/fisiologia , Análise Multivariada , Valor Preditivo dos Testes , Análise de Componente Principal , Prognóstico , Leitura , Reprodutibilidade dos Testes , Percepção Espacial/fisiologia , Teste de Stroop , Teste de Sequência Alfanumérica , Comportamento Verbal , Testes de Associação de PalavrasRESUMO
The aim of this research was to assess similarity in cognitive factor structures underlying neuropsychological test performance of elders belonging to three clinical groups: Alzheimer's disease (AD), Mild Cognitive Impairment (MCI), and normal elderly. We administered a battery of neuropsychological tests to 214 elderly participants in the groups. First, the underlying cognitive structure of a Combined-Set of AD, MCI, and Control subjects was determined by Principal Components Analysis (PCA), including quantitative relationships (loadings) between the test measures and the factors. The PCA resolved 17 neuropsychological test measures into 6 interpretable factors, accounting for 78% of the variance. This cognitive structure was compared with separate cognitive structures from an AD-Set, an MCI-Set, and a Control-Set (different individuals in each set) in additional PCA using Procrustes factor rotation. Analysis of congruence coefficients between each set and the Combined-Set by a bootstrapping statistical procedure supported the factor invariance hypothesis. These close similarities across groups in their underlying neuropsychological dimensions support the use of a common metric system (the factor structure of a Combined-Set) for measuring neuropsychological factors in all these elderly individuals.
RESUMO
Neuropsychological assessment aids in the diagnosis of Alzheimer's disease (AD) by objectively establishing cognitive impairment from standardized tests. We present new criteria for diagnosis that use weighted combined scores from multiple tests. Our method employs two multivariate analyses: principal components analysis (PCA) and discriminant analysis. PCA (N = 216 participants) created more interpretable cognitive dimensions by resolving 49 test measures in our neuropsychological battery to 13 component scores for each participant. The component scores were used to build discriminant functions that classified each participant as either an early-stage AD (N = 55) or normal elderly (N = 78). Our discriminant function performed with high accuracy, sensitivity, and specificity (nearly all >90%) in the development, a cross-validation, and a new-subjects validation. When contrasted to two different traditional empirical methods for diagnosis (using cutscores and defining AD as falling below 5% on two or more test domains), our results suggested that the multivariate method was superior in classification (approximately 20% more accurate).