Las orexinas como biomarcadores para demencia tipo Alzheimer y relación con síntomas neuropsiquiátricos / Orexins as biomarkers for Alzheimer dementia and their relationship with neuropsychiatric symptoms

RESUMEN: Los biomarcadores más estudiados en la demencia tipo Alzheimer (DA) son los niveles elevados de Aβ42 y de proteína Tau en líquido cefalorraquídeo. Dada la complejidad de la sintomatología cognitiva y síntomas neuropsiquiátricos (SNP) de esta patología, algunos estudios recientes proponen sustancias como las orexinas, como blanco terapéutico de DA y SNP. El presente trabajo tiene como objetivo revisar publicaciones científicas recientes que hayan analizado la asociación entre orexinas, SNP y DA en humanos, algunos modelos animales y que hayan evaluado a las orexinas como posibles biomarcadores tanto para investigación como en el área clínica. En esta revisión también se describen los estudios que sugieren a las orexinas como un posible biomarcador en la DA, dada su relación con el Aβ42 y la proteína Tau, y otros estudios que las asocian con presencia de SNP, especialmente alteración del sueño. Se plantea la hipótesis de que la presencia de SNP en DA se asocia con las orexinas, debido a que este sistema influye en el funcionamiento hipotalámico y de forma indirecta en áreas cerebrales que regulan el comportamiento. Sin embargo, aún falta mayor investigación, principalmente de estudios longitudinales para conocer claramente la influencia de las orexinas en los SNP.

ABSTRACT The most studied biomarkers in Alzheimer's dementia (AD) are elevated levels of Aβ42 and Tau protein in cerebrospinal fluid. Given the complexity of the cognitive symptomatology and neuropsychiatric symptoms (NPS) of this pathology, some recent studies propose substances such as orexins as a therapeutic target for AD and NPS. The present work aims to review recent scientific publications that have analyzed the association between orexins, PNS and AD in humans. There are some animal models that have evaluated orexins as possible biomarkers both for research and in the clinical area. This review also describes studies that suggest orexins as possible biomarkers in AD, given their relationship with Aβ42 and Tau protein, and other studies that associate them with the presence of SNPs, especially sleep disturbance. It is hypothesized that the presence of SNPs in AD is associated with orexins, because this system influences hypothalamic functioning and indirectly in brain areas that regulate behavior. However, further research is still lacking, mainly longitudinal studies to clearly know the influence of orexins on SNPs.

Active music therapy in dementia: results from an open-label trial / Musicoterapia ativa na demência: resultados de um estudo aberto

OBJECTIVE: Cognitive, neuropsychiatric and functional deficits are core symptoms of dementia. Non- -pharmacological interventions, such as music therapy, when used in conjunction with pharmacological treatment, have the potential to alleviate these symptoms. The purpose of this preliminary study is to examine the active music therapy on cognition and neuropsychiatric symptoms in the elderly with mild and moderate dementia. METHODS: The initial sample consisted of outpatients with dementia (N = 15) and their family members or caregivers (N = 15). Two dyads did not complete the assessments before intervention and were excluded from the analysis. Thirteen females (N = 13) comprised the final sampled and were diagnosed with Alzheimer's disease (N = 10), vascular dementia (N = 2) and mixed dementia (N = 1), at mild (N = 11) and moderate (N = 2) dementia stage. Participants were enrolled in an open-label trial of active music therapy group, set to take place once weekly for 60 minutes over a period of 12 weeks. RESULTS: Participants experienced a slight improvement on cognition measured with Mini-Mental State Examination (p = 0.41), although without statistical significance and a statistically significant decrease in anxiety (p = 0.042) in post-intervention. There were no significant effects on quality of life and caregiver burden. CONCLUSIONS: Active music therapy is a promising intervention with good acceptance among participants. More studies with larger sample sizes are needed to confirm its effects and efficacy in cognitive and neuropsychiatric symptoms in dementia.

OBJETIVO: Distúrbios cognitivos, comportamentais e funcionais são sintomas nucleares na demência. Intervenções não farmacológicas, como a musicoterapia, quando usadas em conjunto com o tratamento farmacológico, têm o potencial de aliviar esses sintomas. O objetivo deste estudo preliminar é examinar a musicoterapia ativa na cognição e nos sintomas neuropsiquiátricos em idosos com demência leve e moderada. MÉTODOS: A amostra inicial foi composta por pacientes ambulatoriais com demência (N = 15) e seus familiares ou cuidadores (N = 15). Duas duplas não completaram as avaliações antes da intervenção e foram excluídas da análise. Treze mulheres (N = 13) compuseram a amostra final e foram diagnosticadas com doença de Alzheimer (N = 10), demência vascular (N = 2) e demência mista (N = 1), nos estágios leve (N = 11) e moderado (N = 2). Os participantes foram inscritos em um estudo aberto de grupo de musicoterapia ativa, programado para ocorrer uma vez por semana, com duração de 60 minutos, durante o período de 12 semanas. RESULTADOS: Os participantes experimentaram uma discreta melhora cognitiva medida pelo Miniexame do Estado Mental (p = 0.41), embora sem significância estatística, e uma diminuição estatisticamente significativa na ansiedade (p = 0.042) na pós-intervenção. Não houve efeitos significativos na qualidade de vida e sobrecarga do cuidador. CONCLUSÕES: A musicoterapia ativa é uma intervenção promissora, com boa aceitação entre os participantes. Mais estudos com amostras maiores são necessários para confirmar seus efeitos e eficácia em sintomas cognitivos e neuropsiquiátricos na demência.

Neuropsiquiatría del síndrome de Susac: a propósito de un caso / Neuropsychiatry of Susac Syndrome: a Case Report

RESUMEN El síndrome de Susac es una entidad clínica poco frecuente, posiblemente mediada por un proceso autoinmune; la tríada clásica se compone de retinopatía, disminución en la agudeza auditiva y síntomas neuropsiquiátricos (encefalopatía). Hay pocos casos descritos con sintomatología neuropsiquiátrica como la sintomatología principal. Presentamos un caso de síndrome de Susac, que corresponde a una mujer de 34 arios, con predominio de sintomatologia neuropsiquiátrica, caracterizada por un síndrome de Klüver-Bucy parcial, un síndrome apático, risa y llanto patológico y alteraciones cognitivas de predominio atencional; dichos síntomas mejoraron cualitativamente con el uso de terapia inmunológica. Este caso revela la importancia de las manifestaciones neuropsiquiátricas como presentación clínica en pacientes con entidades neurológicas.

ABSTRACT Susac syndrome is a rare clinical condition, possibly mediated by an autoimmune process; the classic triad is composed of retinopathy, decreased hearing acuity and neuropsychiatric symptoms (encephalopathy). There are few cases reported with neuropsychiatric symptoms as the main manifestation. We present a case of Susac syndrome in a 34-year-old female with a predominance of neuropsychiatric symptoms, characterised by partial Klüver-Bucy syndrome, apathy syndrome, pathological laughter and crying, and cognitive dysfunction predominantly affecting attention, which showed a qualitative improvement with the use of immunological therapy. This case report highlights the importance of neuropsychiatric manifestations as clinical presentation in patients with neurological conditions.

The Relation between Behavioral, Emotional and Cognitive Apathy and Everyday Executive Dysfunction in Alcoholic Korsakoff's Syndrome

ABSTRACT Background: Apathy is an important neuropsychiatric symptom in alcohol-related cognitive impairment in general, and Korsakoff's syndrome in specific. However, research in patients with Korsakoff's syndrome on the multifaceted nature of apathy is lacking. Objectives: Aim of the current study was to examine behavioral, cognitive and emotional apathy in alcoholic Korsakoff patients, also investigating the association with overall cognitive and executive dysfunction. Methods: We studied 43 patients with Korsakoff's syndrome (mean age 60.9, SD=6.5, range 38-70) using the Apathy Evaluation Scale - Informant Version (AES-I) and also administered the Montreal Cognitive Assessment and the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) as a measure of daily executive problems. Results: In our sample, 76% of the Korsakoff patients were classified as being apathetic. AES-I scores correlated with overall cognitive function and were related to observer-rated daily executive problems. Discussion: Apathy is highly prevalent in Korsakoff patients and related to overall cognitive dysfunction and everyday executive problems. Our results stress the need to further examine underlying mechanisms of apathy in Korsakoff patients and the need for interventions aimed at reducing apathy.

Anxiety Disorders - Assessment and Management in General Practice

@#The objective of this article is to provide an update on the diagnosis, assessment, and management of anxiety disorders in adults. This article covers the following disorders: panic disorder, panic attacks, specific phobia, social anxiety disorder and generalized anxiety disorder. Selective mutism and separation anxiety disorder, being childhood anxiety disorders, will not be covered. Obsessive compulsive disorder and post-traumatic stress disorder, which are not categorized as anxiety disorders in DSM-5, will not be covered. Anxiety and related disorders are common mental health disorders but are under-diagnosed and undertreated. Most cases of anxiety disorders present first to the primary care physician and can be managed in primary care. It is important to take a detailed history of the patient’s symptoms and their severity and duration, enquire about psychosocial stressors, as well as symptoms that may be suggestive of a medical condition and also to assess suicidality. A combined approach of psycho-education, relaxation training, and medications give the best results. SSRIs are first line pharmacologic treatment for most anxiety disorders. There is a need to stress that benzodiazepines have no role in the longterm treatment of anxiety disorders. They should not be given for more than 2 to 4 weeks. Treatment for generalized anxiety disorder should be for at least 32 weeks as high relapse rates are reported after discontinuing medications.

Neuropsychiatric symptoms and executive function impairments in Alzheimer's disease and vascular dementia: The role of subcortical circuits / Sintomas neuropsiquiátricos e prejuízos na função executiva na doença de alzheimer e demência vascular: o papel dos circuitos subcorticais

ABSTRACT Neuropsychiatric symptoms (NPS) in dementia are prevalent, under-recognized and little studied regarding their pathophysiological aspects. The pathophysiological mechanism, as well as the possible role of vascular lesions in the genesis of these symptoms, are still matters of debate. Objective: to describe and compare the prevalence and severity of NPS in subjects with Alzheimer's disease (AD) and vascular dementia (VaD). Methods: a cross-sectional study involving 82 outpatients, divided into two groups (AD × VaD), was conducted. Patients were submitted to the Cambridge Cognitive Test (CAMCOG), the Clock Drawing Test (CLOX 1 and 2), the Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating (CDR) scale. Neuroimaging was scored using the de Leon and Fazekas scales. Results: 90.8% of the patients had at least one neuropsychiatric symptom. There were statistical differences on the CLOX test and in the apathy symptoms between AD and VaD groups. Apathy and disinhibition proved more prevalent in patients with higher vascular load. Conclusion: apathy and impaired executive function may reflect vascular damage in subcortical circuits in dementia patients.

RESUMO Sintomas neuropsiquiátricos na demência são prevalentes, pouco reconhecidos e ainda pouco estudados quanto aos aspectos fisiopatológicos. O mecanismo fisiopatológico, assim como o possível papel das lesões vasculares na gênese destes sintomas ainda são motivos de debate. Objetivo: descrever e comparar a prevalência e severidade dos sintomas entre a doença de Alzheimer (DA) e demência vascular (DV). Métodos: estudo transversal que incluiu 82 pacientes selecionados, divididos em dois grupos (DA × DV). Foram submetidos ao teste cognitivo de Cambridge (CAMCOG), teste do desenho do relógio (CLOX 1 e 2), inventário neuropsiquiátrico (INP) e avaliação clínica do estágio da demência (CDR). Avaliação dos índices de neuroimagem foram pelo escore de de Leon e Fazekas. Resultados: 90.8% dos pacientes apresentavam pelo menos um sintoma neuropsiquiátrico. Houve diferença estatísticas no CLOX e sintoma apatia entre DA e DV. Apatia e desinibição demonstraram ser mais prevalentes nos pacientes com maior carga vascular. Conclusão: Apatia e alteração na função executiva podem refletir danos vasculares nos circuitos subcorticais naqueles pacientes com demência.

Pellagra induced psychosis: a rare presentation

Pellagra is a nutritional deficiency disease associated with low levels of niacin (vitamin B3). Neuropsychiatric symptoms are rare and are difficult to be diagnosed by clinicians in a timely manner. A 35 years old male was brought with complaints of generalized weakness, decreased appetite and work impairment since past 4 years. Scaly and itching skin rashes have also been present since 3 months followed by hearing voices, suspiciousness and agitated behaviour since one month. On examination, he had pruritic skin rashes over hands which extended over face and neck. His diet comprised mainly of jowar and maize and had history of occasional alcohol use. With an initial diagnosis of psychosis, the patient was started on oral olanzapine. Laboratory and imaging investigations were within normal limits. Dermatology referral confirmed pellagra clinically. The patient was started on injectable multivitamins for 14 days and later shifted to oral multivitamins. Patient showed significant improvement in his skin and neuropsychiatric symptoms. Present case suggests that physicians need to remain vigilant because it is easy to overlook such patients. Pellagra has an insidious onset and psychiatric symptoms appear rare and late in the course when disease is allowed to progress.

Efficacy of treadmill training on neuropsychiatric symptoms and quality of life among elderly Alzheimer's disease / 中国实用护理杂志

Objective@#To analyze effect of Treadmill Training on neuropsychiatric symptoms and quality of life in elderly patients with Alzheimer′s disease.@*Methods@#From May 2018 to November 2018, the experimental design was adopted. The patients with 55-75 years old AD, the First Affiliated Hospital of Quanzhou Fujian Medical University were randomly divided into groups. Group (treadmill training, 68 patients), control group (no intervention, 68 patients). The two groups were evaluated before the training and 20 weeks after training, using the Neuropsychology Scale (NPI-Q) and the Alzheimer's disease Quality of Life Questionnaire (QOL-AD), and the t-test, two-factor repeated measures analysis of variance, etc. Statistical methods for data analysis.@*Results@#There were no significant differences in neuropsychiatric scores and QOL scores between the two groups before training (P>0.05). After training through a 20-week treadmill, the total score of neuropsychiatric symptoms in patients with Alzheimer's disease in the experimental group (t=-1.317, P=0.204 before training; t=-10.01, P=0.046 after 20 weeks of training), affective symptoms (Before training, t=-1.684, P=0.092; t=-11.26, P=0.043 after 20 weeks of training, psychiatric symptoms (t=1.168 before training, P=0.235; t=-9.94 after training for 20 weeks, P=0.034)), behavioral symptoms (t=1.952 before training, P=0.129; t=-3.61, P=0.028 after 20 weeks of training), and QOL total score (t=1.452, P=0.140 before training; t=22.27 after training, P=0.040) were statistically different; and the improvement of neuropsychiatric symptoms in the experimental group was significantly different from that in the control group (F=23.10, P=0.000), while the QOL of the experimental group was also significantly different from the control group (t=- 8.88, P=0.000).@*Conclusion@#Non-pharmacological treatment with treadmill training can improve neuropsychiatric symptoms and improve quality of life in elderly AD patients.

Research progress of post-stroke apathy syndrome / 中国脑血管病杂志

Stroke patients are often affected by psychological factors and neuropsychiatric disorders. Posl-stroke apathy syndrome can have a negative impact on the recovery of the patient's body,and reduce the quality of life of patients and increase the burden of care. However, current posl-stroke apathy syndrome is not fully recognized and is seriously underestimated. Therefore, in order to provide clinicians with assistance in the diagnosis and treatment of post-stroke apathy syndrome, this article reviews the conception,epidemiology,pathogenesis,diagnosis and management of post-stroke apathy syndrome.

Efficacy of treadmill training on neuropsychiatric symptoms and quality of life among elderly Alzheimer's disease / 中国实用护理杂志

Objective To analyze effect of Treadmill Training on neuropsychiatric symptoms and quality of life in elderly patients with Alzheimer′s disease. Methods From May 2018 to November 2018, the experimental design was adopted. The patients with 55-75 years old AD, the First Affiliated Hospital of Quanzhou Fujian Medical University were randomly divided into groups. Group (treadmill training, 68 patients), control group (no intervention, 68 patients). The two groups were evaluated before the training and 20 weeks after training, using the Neuropsychology Scale (NPI-Q) and the Alzheimer's disease Quality of Life Questionnaire (QOL-AD), and the t-test, two-factor repeated measures analysis of variance, etc. Statistical methods for data analysis. Results There were no significant differences in neuropsychiatric scores and QOL scores between the two groups before training (P＞0.05). After training through a 20-week treadmill, the total score of neuropsychiatric symptoms in patients with Alzheimer's disease in the experimental group (t=-1.317, P=0.204 before training; t=-10.01, P=0.046 after 20 weeks of training), affective symptoms ( Before training, t=-1.684, P=0.092; t=-11.26, P=0.043 after 20 weeks of training, psychiatric symptoms (t=1.168 before training, P=0.235; t=-9.94 after training for 20 weeks, P=0.034) ), behavioral symptoms (t=1.952 before training, P=0.129; t=-3.61, P=0.028 after 20 weeks of training), and QOL total score (t=1.452, P=0.140 before training; t=22.27 after training, P=0.040) were statistically different; and the improvement of neuropsychiatric symptoms in the experimental group was significantly different from that in the control group (F=23.10, P=0.000), while the QOL of the experimental group was also significantly different from the control group (t=- 8.88, P=0.000). Conclusion Non-pharmacological treatment with treadmill training can improve neuropsychiatric symptoms and improve quality of life in elderly AD patients.

Demencia y factores de riesgo en cuidadores informales / Dementia and risk factors in informal caregivers

Introducción: Los síndromes demenciales son unas de las principales causas de dependencia en personas mayores y la mayor contribuyente de alteraciones en la salud del cuidador. Objetivos: Estimar la asociación entre demencia, estadio de la enfermedad y síntomas neuropsiquiátricos en personas demenciadas, con morbilidad física y psicológica en cuidadores principales. Métodos: Análisis secundario de la base de datos del estudio Envejecimiento y Alzheimer, un estudio poblacional en personas de 65 años y más en Cuba. Se seleccionaron 323 cuidadores principales de personas demenciadas en La Habana y Matanzas, durante el periodo 2003-2007. Se aplicó el protocolo diagnóstico 10/66 y la Escala de Estadificación Clínica a las personas demenciadas, así como una entrevista sobre datos sociodemográficos y factores de riesgo, el Inventario Neuropsiquiátrico y Escala de sobrecarga de Zarit a los cuidadores en estudio, para determinar los factores de riesgo asociados a la morbilidad física y psicológica en los mismos. Resultados: La morbilidad física y psicológica en los cuidadores es elevada a medida que avanza la enfermedad. Esta variable se relacionó con la presencia de síntomas neuropsiquiátricos en personas demenciadas (OR= 1,03; 1,00-1,09 IC 95 por ciento) y los elevados niveles de sobrecarga en los cuidadores (OR= 4,88; 2,16-11,02 IC 95 por ciento). Conclusiones: la morbilidad física y psicológica se relacionó con la severidad de los síntomas neuropsiquiátricos presentes en las personas demenciadas y la sobrecarga en los cuidadores(AU)

Manifestaciones Neuropsiquiatricas De La Enfermedad De Whipple En Una Adolescente: A Propósito De Un Caso / Neuropsiquiatric Manifestations Of Whipple Disease In An Adolescent: Case Report

RESUMEN La enfermedad de Whipple (EW) es una rara infección sistémica crónica producida por el actinomiceto Tropheryma Whipplei. Las manifestaciones clínicas son principalmente intestinales, si bien en ocasiones se asocian presentaciones extraintestinales (articulares, cardiacas, pulmonares neurológicas…), e incluso pueden presentarse sólo éstas últimas. Se presenta una paciente de 15 años derivada al servicio de Psiquiatría , con el diagnóstico de depresión, con un evolución de 6 meses con empeoramiento, ingreso por intento autolítico y paralelamente refiere sintomatología neurológica atípica. Se le remite a Neurología para descartar patología orgánica, incluyendo patologías autoinmunes (encefalitis antiNMDA), encontrándose en el estudio, PCR positivo a Tropheryma Whipplei en LCR, diagnosticándose de enfermedad de Whipple con afectación neurológica. Se realizó tratamiento antibiótico según las pautas establecidas, repitiéndose al finalizar el tratamiento la punción lumbar, resultando ésta negativa y con mejoría clínica tanto neurológica como psiquiátrica.

SUMMARY Whipple disease (WD) is a rare chronic systemic infection caused by the actinomycete Tropheryma Whipplei. The clinical manifestations are mainly intestinal, although occasionally may present extraintestinal locations (joints, heart, pulmonary, central nervous system ...) , and even the last can be the only symptom. We present a 15-year-old female patient referred to the psychiatry service, with a diagnosis of depression, with a 6-month evolution with worsening, admission due to autolytic attempt and, at the same time, atypical neurological symptomatology. She is referred to Neurology to rule out organic pathology, including autoimmune pathologies (antiNMDA encephalitis, ...), finding in the study, PCR positive Tropheryma Whipplei, and being diagnosed of Whipple disease with neurological involvement. Antibiotic treatment was performed according to the established guidelines, repeated at the end of the treatment the lumbar puncture, resulting this negative and with clinical neurological improvement as well as psychiatric.

Neuropsychiatric symptoms in vascular dementia: Epidemiologic and clinical aspects / Sintomas neuropsiquiátricos na demência vascular: aspectos clínicos e epidemiológicos

ABSTRACT Dementia is a general term for a heterogeneous group of organic neurodegenerative diseases. Cerebrovascular causes account for 20% of cases. Objective: To describe the clinical and epidemiological features of individuals aged >60 years diagnosed with vascular dementia (VD) or mixed dementia (MxD) in a referral hospital for dementia. Methods: A descriptive, retrospective study was carried out from 2014 to 2017 involving elderly individuals (≥60 years) with VA or MxD. Patients presenting other forms of dementia or in use of medication that mimics cognitive disorders were excluded. The 12-item Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms (NPS). Results: 81.1% of the patients presented NPS and only 15% had two or more symptoms. Apathy was the most frequent NPS (56.6%). There was an association between CDR score 1 or 2 and NPS (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusion: Most patients had a single symptom, predominantly apathy. There was an association between mild-to-moderate dementia and NPS.

RESUMO Demência é uma terminologia geral para um grupo heterogêneo de doenças orgânicas e neurodegenerativas. As causas cerebrovasculares são responsáveis por 20% dos casos. Objetivo: Descrever as características clínicas e epidemiológicas de indivíduos maiores de 60 anos diagnosticados com demência vascular ou mista em hospital de referência em demência. Métodos: Estudo retrospectivo descritivo de 2014 a 2017 em idosos com demência. Outras formas de demência ou uso de medicamentos que mimetizem distúrbios cognitivos foram excluídos. O inventário neuropsiquiátrico de 12 itens foi usado para avaliar os sintomas neuropsiquiátricos (SNP). Resultados: 81.1% dos pacientes apresentaram SNP, apenas 15% tiveram dois ou mais. Apatia foi o mais frequente (56,6%). Houve associação entre CDR 1 ou 2 e SNP (OR = 6.16, 95% CI: 1.36-27.9, p = 0.02). Conclusão: Geralmente há um sintoma isolado, sendo apatia o principal. Encontramos associação entre demência leve e moderada e SNP.

Limbic Encephalitis Manifesting as Selective Amnesia and Seizure-like Activity: A Case Report

Limbic encephalitis (LE) is characterized by short-term memory loss, disorientation, agitation, seizures, and histopathological evidence of medial temporal lobe inflammation. Leucine-rich, glioma inactivated 1 (LGI-1) is an auto-antigen associated with LE. We report a 37-year-old male patient with LGI-1-related LE who presented with recurrent episodes of selective amnesia, seizure-like activity, confusion, and personality change. His symptoms were significantly improved with steroid therapy. Thorough differential diagnosis with consideration for autoimmune encephalitis should be in patients with presentation of symptoms, such as memory impairment, personality change and seizure-like activity, especially when other neurological diagnoses are excluded.

Más allá del deterioro cognitivo: síntomas neuropsiquiátricos en demencias neurodegenerativas / Beyond Cognitive Impairment: Neuropsychiatrie Symptoms in Neurodegenerative Dementias

Resumen En la medida que aumenta la expectativa de vida se hace mayor el número de personas diagnosticadas de demencia neurodegenerativa. Aunque es central en la demencia el deterioro cognitivo, los síntomas neuropsiquiátricos (SNP) son muy importantes, pues aumentan los costes directos e indirectos de la enfermedad al generar más morbilidad, estrés del cuidador, uso de medicamentos e institucionalización. Por otro lado, es importante conocer la naturaleza de los SNP, pues varían entre los distintos tipos de demencia y pueden ayudar a determinar la etiología del deterioro cognitivo. El manejo de primera línea de los SNP en demencia es no farmacológico; se busca inicialmente identificar las causas internas y externas de los SNP y generar intervenciones encaminadas a modificar patrones conductuales en el paciente y su cuidador, además de introducir en el ambiente en que se desenvuelve el paciente cambios que puedan mejorar su desempeño y su conducta. Si estas intervenciones no tienen utilidad, se pasa al abordaje farmacológico, que incluye el uso de antidemenciales, antipsicóticos, antidepresivos, estabilizadores del estado de ánimo y benzodiacepinas; ningún psicofármaco tiene eficacia suficiente, y la mayoría de ellos tienen efectos adversos importantes, por lo que es necesario un estudio individual y la implementación de estrategias no farmacológicas antes de considerar los medicamentos para el tratamiento de los SNP en demencia.

Abstract As life expectancy increases, the number of people diagnosed with neurodegenerative dementia also increases. Although cognitive impairment is central in dementia, neuropsychiatric symptoms (NPS) are very important because they increase both direct and indirect costs by generating greater morbidity, caregiver distress, use of medication and institutionalisation. Furthermore, it is important to understand the nature of NPS, since they can vary across the different types of dementia and may provide useful clinical information regarding the aetiology of cognitive impairment. The first-line management of NPS in dementia is non-pharmacological; internal and external causes should first be identified and strategies developed to modify the behavioural patterns of the patient and their caregiver. In addition, changes in the patient's surroundings that may improve patient performance and behaviour should be encouraged. If these practices are not satisfactory, a pharmacological treatment approach is adopted that includes anti-dementia drugs, antipsychotics, antidepressants, mood stabilisers and benzodiazepines. However, psychoactive drugs do not offer sufficient efficacy and most of them have significant adverse effects, so each patient should be individually assessed, together with the implementation of non-pharmacological strategies, before deciding on pharmacological treatment for the management of NPS in dementia.

Encefalitis por anticuerpos contra receptores de N-metil-D-aspartato y síndrome de DRESS secundario a fenitoína: Reporte de un caso / Encephalitis by anti-N-Methyl-D-Aspartate receptor antibodies and DRESS syndrome secondary to phenytoin: A case report

La encefalitis debida a anticuerpos contra receptores N-metil-D-aspartato (NMDA)es una entidad potencialmente tratable, caracterizada por síntomas neuropsiquiátricos que incluyen crisis epilépticas, alteración de conciencia, catatonía y trastornos autonómicos, y desencadenada por una respuesta inmunológica mediada por antígenos. A su vez, el síndrome DRESS (sigla en inglés de Reacción a drogas con eosinofília y síntomas sistémicos) es un cuadro de hipersensibilidad retardada mediada por células, frecuentemente asociada a fármacos antiepilépticos aromáticos. Se presenta el caso de una paciente joven que debutó con crisis epilépticas inicialmente fármaco-sensibles, desarrolló luego el síndrome de DRESS secundario a fenitoína. Cursó posteriormente con trastornos de memoria y lenguaje, alteraciones conductuales y estado catatónico y presentó anticuerpos contra receptores NMDA en el líquido cefalorraquídeo. Ambas entidades respondieron a inmunoterapia con corticoides, lo cual contribuiría a explicar una asociación fisiopatogénica entre estas dos entidades inmunomediadas.

N-Methyl-D-Aspartate receptor encephalitis is a potentially treatable entity characterized by neuropsychiatric symptoms including epileptic seizures, disruption of consciousness, catatonia, and autonomic disorders, and triggered by an immunological response mediated by an antigen. In turn, the DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a delayed cell-mediated hypersensitivity reaction, frequently associated with antiepileptic aromatic drugs. The case is presented of a young patient who debuted with epileptic seizures initially drug-sensitive, developedthen DRESS syndrome secondary to the use of phenytoin, and later presented disorders of memory and language, behavioral alterations and catatonic state, and presented anti- NMDA receptor antibodies in CSF. Both entities responded to corticoid immuno-therapy, which could contribute to explain a pathogenic association between these two immunomediated entities.

Utility of the Neuropsychiatric Inventory Questionnaire (NPI-Q) in the assessment of a sample of patients with Alzheimer's disease in Chile / Utilidade do questionário de inventário neuropsiquiátrico (npi-q) na avaliação de uma amostra de pacientes com doença de Alzheimer no Chile

ABSTRACT. The Neuropsychiatric Inventory Questionnaire (NPI-Q) is an informant-based instrument that measures the presence and severity of 12 Neuropsychiatric Symptoms (NPS) in patients with dementia, as well as informant distress. Objective: To measure the psychometric properties of the NPI-Q and the prevalence of NPS in patients with Alzheimer's disease (AD) in Chile. Methods: 53 patients with AD were assessed. Subjects were divided into two different groups: mild AD (n=26) and moderate AD (n=27). Convergent validity was estimated by correlating the outcomes of the NPI-Q with Neuropsychiatric Inventory (NPI) scores and with a global cognitive efficiency test (Addenbrooke's Cognitive Examination - Revised - ACE-R). Reliability of the NPI-Q was analysed by calculating its internal consistency. Prevalence of NPS was estimated with both the NPI and NPI-Q. Results: Positive and significant correlations were observed between the NPI-Q, the NPI, and the ACE-R (r=0.730; p<0.01 and 0.315; p<0.05 respectively). The instrument displayed an adequate level of reliability (Cronbach's alpha=0.783). The most prevalent NPS were apathy/indifference (62.3%) and dysphoria/depression (58.5%). Conclusion: The NPI-Q exhibited acceptable validity and reliability indicators for patients with AD in Chile, indicating that it is a suitable instrument for the routine assessment of NPS in clinical practice.

RESUMO. O Questionário de Inventário Neuropsiquiátrico (NPI-Q) é um instrumento baseado em informantes que mede a presença e a gravidade de 12 Sintomas Neuropsiquiátricos (NPS) em pacientes com demência, bem como o sofrimento do informante. Objetivo: Avaliar as propriedades psicométricas do NPI-Q e a prevalência de NPS em pacientes com doença de Alzheimer (DA). Métodos: Foram avaliados 53 pacientes com DA. Eles foram divididos em dois grupos diferentes: AD leve (n=26) e AD moderado (n=27). A validade convergente foi estimada correlacionando os resultados do NPI-Q com os escores do Inventário Neuropsiquiátrico (NPI) e um teste de eficiência cognitiva global (Addenbrooke's Cognitive Examination - Revised - ACE-R). A confiabilidade do NPI-Q foi analisada pelo cálculo da sua consistência interna. A prevalência de NPS foi estimada com NPI e NPI-Q. Resultados: Foram observadas correlações positivas e significativas entre NPI-Q, NPI e ACE-R (r=0,730; p<0,01 e 0>315; p<0>05). O instrumento apresentou um nível adequado de confiabilidade (alfa de Cronbach=0J83). Os NPS mais prevalentes foram apatia/indiferença (62,3%) e disforia/depressão (58,5%). Conclusão: O NPI-Q apresenta indicadores de validade e confiabilidade aceitáveis em pacientes com DA, o que indica que é um instrumento adequado para a avaliação rotineira de NPS na prática clínica.

Efficacy of music therapy in the neuropsychiatric symptoms of dementia: systematic review / Eficácia da musicoterapia nos sintomas neuropsiquiátricos da demência: revisão sistemática

ABSTRACT Objective A large number of psychosocial interventions in dementia are based on music activities and music therapy interventions. We aim at assessing the efficacy of music therapy in the neuropsychiatric symptoms of people with dementia. Methods This systematic review is according to the methodology suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched for articles in PubMed, Web of Knowledge Cross Search, Cochrane Library, Scopus and Lilacs/Bireme databases published from 2005 to 2016. The search keywords included “early onset” and “late onset” combined with “dementia”, “Alzheimer”, “vascular dementia”, “mixed dementia”, “frontotemporal dementia”, “neuropsychiatric symptoms”, “behavioral disturbances”, “behavioral and psychological symptoms of dementia” and “music therapy”. The studies were categorized according to its efficacy on the decline of neuropsychiatric symptoms and improvement of cognitive function, quality of life and well-being. Results We selected 12 out of 257 papers. Music therapy interventions were applied individually or in group setting, using active or receptive technique. In general, studies indicated the efficacy of music therapy on the decline of depression, agitation and anxiety. There were heterogeneity of interventions, methodological design and instruments of evaluation among the studies. Conclusions Although there are reports of the efficacy of music therapy on the decline of neuropsychiatric symptoms of dementia, the area still needs randomized studies aimed at the solution of important methodological problems like the lack of standardized approaches.

RESUMO Objetivo Muitas intervenções psicossociais na demência estão baseadas em atividades musicais e intervenções de musicoterapia. Nosso objetivo consiste em avaliar a eficácia das intervenções de musicoterapia nos sintomas neuropsiquiátricos de pessoas com demência. Métodos Esta revisão sistemática está de acordo com a metodologia sugerida pela Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Foi realizada busca por artigos nas bases de dados PubMed, Web of Knowledge Cross Search, Cochrane Library, Scopus e Lilacs/Bireme publicados de 2005 a 2016. As palavras-chave incluíram descritores como “início precoce” e “início tardio” combinados com “demência”, “Alzheimer”, “demência vascular”, “demência mista”, “demência frontotemporal”, “sintomas neuropsiquiátricos”, “distúrbios comportamentais”, “sintomas comportamentais e psicológicos da demência”, “musicoterapia”. Os estudos foram categorizados segundo sua eficácia na redução dos sintomas neuropsiquiátricos e na melhora da função cognitiva, qualidade de vida e bem-estar. Resultados Foram selecionados 12 dos 257 artigos encontrados. As intervenções de musicoterapia foram aplicadas individualmente ou em grupo, utilizando técnica ativa ou receptiva. Em geral, os estudos indicaram a eficácia da musicoterapia na diminuição da depressão, agitação e ansiedade. Houve heterogeneidade das intervenções, desenho metodológico e instrumentos de avaliação entre os estudos. Conclusões Embora haja relatos de eficácia da musicoterapia na diminuição dos sintomas neuropsiquiátricos da demência, a área ainda necessita de estudos randomizados que visem à solução de problemas metodológicos importantes, como a falta de abordagens padronizadas.

Important differential in a patient presenting with neuropsychiatric symptoms: Anti-N-Methyl-D-Aspartate receptor encephalitis

Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an immune mediated condition, which remains relatively unknown in Malaysia outside tertiary hospitals with neurology unit. It is often misdiagnosed as a psychiatric illness before definitive treatment is instituted. We report here an 18-year-old man who initially presented to the psychiatry unit before he was subsequently diagnosed as having anti-NMDAR encephalitis. To our knowledge, this is the first reported case of anti-NMDAR encephalitis in the east coast of Peninsular Malaysia.

Neuropsychiatric Symptoms and Increased Risks of Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Dementia

OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in dementia and in mild cognitive impairment (MCI). They might be a predictor of progression to dementia. This study aimed to investigate the effects of NPS on the natural course in MCI. METHODS: 306 community-dwelling Korean elderly with MCI from local dementia center were assessed for NPS using Neuropsychiatric Inventory (NPI). Subjects were assessed again after more than a year from baseline. 52 subjects (17.0%) were progressed to dementia. We compared baseline NPI scores between stable and deteriorated groups. RESULTS: Subjects progressing to dementia had a significantly higher prevalence of NPS (45.3% vs. 65.4%) than subjects who remained stable. Delusion (2.8% vs. 9.6%), agitation/aggression (14.6% vs. 26.9%), depression (21.7% vs. 40.4%) and disinhibition (4.3% vs. 19.2%) were more common in deteriorated group. After adjustment for other variables, on logistic regression analysis, only disinhibition at baseline was shown to be a risk factor for progression to dementia (OR=4.88, 95% CI=1.37-17.36, p=0.01, R²=302). CONCLUSION: These findings suggest that NPS in MCI may be a predictor of progression to dementia. NPS may be a useful item including delusion, agitation/aggression, depression, and disinhibition. To study course and nature of NPS may lead to better understanding of Alzheimer's disease.