Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management / Sintomas comportamentais ou neuropsiquiátricos da doença de Alzheimer: psicopatologia e abordagem terapêutica

Abstract Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Resumo Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

Apomorfina y disfunción frontal en la enfermedad de Parkinson / Apomorphine and frontal dysfunction in Parkinson’s disease

Introducción: El trastorno disejecutivo y la apatía son síntomas característicos de la disfunción frontal ligada a la enfermedad de Parkinson. El efecto de la infusión continua subcutánea de apomorfina en la disfunción frontal no se conoce con detalle. Desarrollo: Se ha realizado una búsqueda y análisis de los trabajos publicados más relevantes en este campo. La apomorfina logra mejorías en las pruebas que miden tareas como la planificación, la atención, la fluencia verbal y la apatía. Conclusiones: Debido a su perfil farmacológico distintivo, con mayor actividad sobre los receptores dopaminérgicos de tipo D1, la apomorfina puede resultar beneficiosa en la disfunción frontal de la enfermedad.(AU)

Introduction: Dysexecutive disorder and apathy are characteristic symptoms of frontal dysfunction linked to Parkinson’s disease. The effect of continuous subcutaneous apomorphine infusion is not known in detail. Development: A search for the most relevant studies published to date in this field was carried out, along with their analysis. Apomorphine achieves improvements in tests that measure tasks such as planning, attention, verbal fluency and apathy. Conclusions: Due to its distinctive pharmacological profile, with enhanced activity on D1-type dopaminergic receptors, apomorphine may have beneficial effects on the frontal dysfunction produced by the diseas.(AU)

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia.

INTRODUCTION: Apathy is a negative symptom of schizophrenia and is associated with poor real world functioning. Therefore, it is important to have validated psychometric instruments to assess this symptom. This is the first study to validate the Spanish adaptation of the self-rated version of the Apathy Assessment Scale (AES-S) in patients with schizophrenia. MATERIALS AND METHODS: Naturalistic, cross-sectional, validation study in 104 patients with schizophrenia evaluated using the following scales: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS), and Apathy Evaluation Scale-self-rated version (AES-S). RESULTS: Reliability: Internal consistency (Cronbach's alpha) was 0.908. Convergent validity: The Pearson correlation coefficient between AES-S and CAINS-MAP total scores was -0.483 (p<0.001). For SNS, total and avolition subscale scores were -0.803 and -0.639 (p<0.001), respectively. With the MAP-SR, the correlation coefficient was -0.727 (p<0.001). Divergent validity: The Pearson correlation coefficient between AES-S and PSP total scores was 0.504 (p<0.001). Furthermore, with the CDSS, the correlation coefficient was -0.431 (p<0.001). Discriminant validity: The AES-S discriminated between different levels of illness severity according to CGI-S scores. Factor analysis: A three-component solution explained 57.32% of the variance. Pearson correlations between coefficients were 1-2=0.265, 1-3=0.464, and 2-3=0.060. CONCLUSION: The Spanish AES-S is a reliable and valid instrument for assessing apathy in Spanish patients with schizophrenia. It seems to be appropriate for use in everyday clinical practice as a means of monitoring apathy in these patients.

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia / Validación de la adaptación a español de Europa de la versión de auto-evaluación de la escala de evaluación de la apatía (AES-S) en pacientes esquizofrénicos

Introduction: Apathy is a negative symptom of schizophrenia and is associated with poor real world functioning. Therefore, it is important to have validated psychometric instruments to assess this symptom. This is the first study to validate the Spanish adaptation of the self-rated version of the Apathy Assessment Scale (AES-S) in patients with schizophrenia.Materials and methods: Naturalistic, cross-sectional, validation study in 104 patients with schizophrenia evaluated using the following scales: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS), and Apathy Evaluation Scale-self-rated version (AES-S).Results: Reliability: Internal consistency (Cronbach's alpha) was 0.908. Convergent validity: The Pearson correlation coefficient between AES-S and CAINS-MAP total scores was −0.483 (p<0.001). For SNS, total and avolition subscale scores were −0.803 and −0.639 (p<0.001), respectively. With the MAP-SR, the correlation coefficient was −0.727 (p<0.001). Divergent validity: The Pearson correlation coefficient between AES-S and PSP total scores was 0.504 (p<0.001). Furthermore, with the CDSS, the correlation coefficient was −0.431 (p<0.001). Discriminant validity: The AES-S discriminated between different levels of illness severity according to CGI-S scores. Factor analysis: A three-component solution explained 57.32% of the variance. Pearson correlations between coefficients were 1–2=0.265, 1–3=0.464, and 2–3=0.060. (AU)

Introducción: La apatía es un síntoma negativo de la esquizofrenia, y está asociada a un mal funcionamiento del mundo real. Por tanto, es importante disponer de instrumentos psicométricos validados para valorar este síntoma. Este es el primer estudio que valida la adaptación al español de la versión auto-evaluada de la escala de evaluación de la apatía (AES-S) en pacientes esquizofrénicos.Material y métodos: Estudio naturalista, transversal y de validación realizado en 104 pacientes esquizofrénicos evaluados utilizando las escalas siguientes: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS) y Apathy Evaluation Scale-self-rated version (AES-S).Resultados: Fiabilidad: La consistencia interna (alfa de Cronbach) fue de 0,908. Validez convergente: El coeficiente de correlación de Pearson entre las puntuaciones totales de AES-S y CAINS-MAP fue de −0,483 (p<0,001). Para SNS, las puntaciones totales y de la subescala de abulia fueron de −0,803 y −0,639 (p<0,001), respectivamente. En cuanto a la escala MAP-SR, el coeficiente de correlación fue de −0,727 (p<0,001). Validez divergente: El coeficiente de correlación de Pearson entre las puntuaciones totales de AES-S y PSP fue de 0,504 (p<0,001). Además, en la escala CDSS, el coeficiente de correlación fue de −0,431 (p<0,001). Validez discriminante: La escala AES-S discriminó entre los diferentes niveles de gravedad de la enfermedad, conforme a las puntuaciones CGI-S. Análisis factorial: Una solución de tres componentes explicó el 57,32% de la varianza. Las correlaciones de Pearson entre los coeficientes fueron de 1-2=0,265, 1-3=0,464 y 2-3=0,060. (AU)

The Neuropsychiatry Of Acquired Brain Injury

The psychiatric syndromes derived from acquired brain injury are the behaviouralconsequences of the combination of cognitive,emotional and volitional sequelae. Theirimpact on the quality of life of patients andrelatives is far greater tan the impact ofmotor or sensory deficit. The descriptionof these behavioural presentations and anattempt to understand the formation of thesymptoms will be undertaken. Changes inawareness, empathy, emotional recognitionand regulation are important mediating factors.Behavioural changes mainly take theform of disinhibition or apathy. Psychoticsyndromes, major depression or bipolar disordersare rare. Some delusional ideas respondto changes in the perception of noveltyor to changes in body perception. (AU)

Los síndromes psiquiátricos y los cambios conductuales que se derivan del daño cerebralson las consecuencias de la combinaciónde las alteraciones volitivas, emocionales ycognitivas. El impacto en la calidad de vidade los pacientes y de sus familiares es significativamentemayor que el impacto de las secuelasmotoras o sensoriales. En este artículose aborda la descripción de estos trastornosneuropsiquiátricos y se propone un acercamientoa la comprensión de cómo se gestan.Los cambios en conciencia de situación, empatía,reconocimiento y regulación emocionalson factores mediadores importantes enla formación de los síntomas. Los cambiosconductuales se presentan principalmente enforma de apatía o desinhibición. Los síndromespsicóticos, los trastornos bipolares o ladepresión mayor son muy poco frecuentes.Por otro lado, las ideas delirantes respondena cambios en la percepción de la novedad/familiaridad de los estímulos o a cambios enla percepción del cuerpo que ocurren tras lesionesdel hemisferio derecho. (AU)

Neuropsychiatry of Susac syndrome: A case report.

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.

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.

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

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.

Behavioural Disturbances in Patients with Diagnosis of Neurocognitive Disorder in Bogotá (Colombia). / Alteraciones del comportamiento de pacientes con diagnóstico de trastorno neurocognoscitivo en Bogotá (Colombia).

INTRODUCTION: The main aim of this study is to determine the prevalence of behavioural disturbances (BD) in a group of patients with diagnosis of neurocognitive disorders assessed by a memory clinic in a referral assessment centre in Bogotá, Colombia, in 2015. MATERIAL AND METHODS: This is an observational, retrospective descriptive study of 507 patients with a diagnosis of neurocognitive disorder (according to DSM-5 criteria) evaluated in a referral centre in Bogotá, Colombia, in 2015. RESULTS: Among the group of patients assessed, analyses reveal mean age for minor neurocognitive disorders of 71.04 years, and 75.32 years for major neurocognitive disorder (P <0.001). A total of 62.72% of the sample were female. The most prevalent aetiology of the neurocognitive disorders was Alzheimer's disease, followed by behavioural variant frontotemporal dementia and neurocognitive disorders due to multiple aetiologies. BD occur more frequently in neurocognitive disorder due to behavioural variant frontotemporal dementia (100%), Alzheimer's disease (77.29%) and vascular disease (76.19%). The most prevalent BD in the group assessed were apathy (50.75%), irritability (48.45%), aggression (16.6%), and emotional lability (14.76%). CONCLUSIONS: BD are highly prevalent in patients with diagnosis of major neurocognitive disorder. BD are more prevalent in behavioural variant frontotemporal dementia than any other group. Apathy, irritability, emotional lability and aggression are the BD that occur with greater prevalence in our sample. We discuss the importance of BD in the clinical progression of neurocognitive disorders.

Alteraciones del comportamiento de pacientes con diagnóstico de trastorno neurocognoscitivo en Bogotá (Colombia) / Behavioural Disturbances in Patients with Diagnosis of Neurocognitive Disorder in Bogotá (Colombia)

RESUMEN Introducción: El objetivo de este estudio es determinar la frecuencia de alteraciones conductuales (AC) en un grupo de pacientes con diagnóstico de trastorno neurocognoscitivo (TN) valorado por clínica de memoria en un centro de evaluación en Bogotá, Colombia, durante el ano 2015. Material y métodos: Estudio observacional descriptivo y de corte retrospectivo de 507 pacientes con diagnóstico de trastorno neurocognoscitivo (según criterios del DSM-5), valorados en un centro de referencia en Bogotá en 2015. Resultados: La media de edad de los sujetos con trastorno neurocognoscitivo leve en el momento del diagnóstico era 71,04 arios y la de aquellos con trastorno neurocognoscitivo mayor, 75,32 años (p < 0,001). El 62,72% de la muestra son mujeres. La etiología más frecuente del trastorno neurocognoscitivo fue la enfermedad de Alzheimer probable, seguida por la degeneración lobar frontotemporal, variante conductual, y el trastorno neurocognoscitivo debido a múltiples etiologías. Las AC se presentan con mayor frecuencia en TN debido a degeneración frontotemporal variante conductual (100%), enfermedad de Alzheimer (77,29%) y vascular (76,19%). Las AC más prevalentes en el grupo evaluado fueron la apatía (50,75%), la irritabilidad (48,45%), la agresividad (16,6%) y la labilidad emocional (14,76%). Conclusiones: Las AC son prevalentes en pacientes con diagnóstico de trastorno neurocognoscitivo mayor. Según la etiología del trastorno neurocognoscitivo mayor, las AC son más prevalentes en la degeneración frontotemporal variante conductual. Apatía, irritabilidad, labilidad emocional y agresividad son las AC más comunes en toda la muestra.

ABSTRACT Introduction: The main aim of this study is to determine the prevalence of behavioural disturbances (BD) in a group of patients with diagnosis of neurocognitive disorders assessed by a memory clinic in a referral assessment centre in Bogotá, Colombia, in 2015. Material and methods: This is an observational, retrospective descriptive study of 507 patients with a diagnosis of neurocognitive disorder (according to DSM-5 criteria) evaluated in a referral centre in Bogotá, Colombia, in 2015. Results: Among the group of patients assessed, analyses reveal mean age for minor neurocognitive disorders of 71.04 years, and 75.32 years for major neurocognitive disorder (P < 0.001). A total of 62.72% of the sample were female. The most prevalent aetiology of the neurocognitive disorders was Alzheimer's disease, followed by behavioural variant fronto-temporal dementia and neurocognitive disorders due to multiple aetiologies. BD occur more frequently in neurocognitive disorder due to behavioural variant frontotemporal dementia (100%), Alzheimer's disease (77.29%) and vascular disease (76.19%). The most prevalent BD in the group assessed were apathy (50.75%), irritability (48.45%), aggression (16.6%), and emotional lability (14.76%). Conclusions: BD are highly prevalent in patients with diagnosis of major neurocognitive disorder. BD are more prevalent in behavioural variant frontotemporal dementia than any other group. Apathy, irritability, emotional lability and aggression are the BD that occur with greater prevalence in our sample. We discuss the importance of BD in the clinical progression of neurocognitive disorders.

Validation of a European Spanish adaptation of the Apathy Evaluation Scale-self-rated version (AES-S) in patients with schizophrenia.

INTRODUCTION: Apathy is a negative symptom of schizophrenia and is associated with poor real world functioning. Therefore, it is important to have validated psychometric instruments to assess this symptom. This is the first study to validate the Spanish adaptation of the self-rated version of the Apathy Assessment Scale (AES-S) in patients with schizophrenia. MATERIALS AND METHODS: Naturalistic, cross-sectional, validation study in 104 patients with schizophrenia evaluated using the following scales: Clinical Global Impression-Severity (CGI-S), Personal and Social Performance (PSP), Clinical Assessment Interview for Negative Symptoms (CAINS), Self-report of Negative Symptoms (SNS), Motivation and Pleasure Scale-Self-Report (MAP-SR), Calgary Depression Scale for Schizophrenia (CDSS), and Apathy Evaluation Scale-self-rated version (AES-S). RESULTS: Reliability: Internal consistency (Cronbach's alpha) was 0.908. Convergent validity: The Pearson correlation coefficient between AES-S and CAINS-MAP total scores was -0.483 (p<0.001). For SNS, total and avolition subscale scores were -0.803 and -0.639 (p<0.001), respectively. With the MAP-SR, the correlation coefficient was -0.727 (p<0.001). Divergent validity: The Pearson correlation coefficient between AES-S and PSP total scores was 0.504 (p<0.001). Furthermore, with the CDSS, the correlation coefficient was -0.431 (p<0.001). Discriminant validity: The AES-S discriminated between different levels of illness severity according to CGI-S scores. Factor analysis: A three-component solution explained 57.32% of the variance. Pearson correlations between coefficients were 1-2=0.265, 1-3=0.464, and 2-3=0.060. CONCLUSION: The Spanish AES-S is a reliable and valid instrument for assessing apathy in Spanish patients with schizophrenia. It seems to be appropriate for use in everyday clinical practice as a means of monitoring apathy in these patients.

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.

Depresión y otros trastornos afectivos en la enfermedad de Parkinson / Depression and other affective disorders in Parkinson's disease

RESUMEN Los síntomas no motores son frecuentes en la enfermedad de Parkinson (EP). La depresión, la ansiedad y la apatía son síntomas muy prevalentes en la población afectada. Estos síntomas han demostrado ser determinantes en el deterioro de la calidad de vida de los pacientes con EP y el resultado es un empeoramiento de su estado funcional y cognitivo, además de aumento en la mortalidad. Diversos sistemas de neurotransmisión, como el dopaminérgico y las vías serotoninérgicas y noradrenérgicas, pueden contribuir a la alta aparición de depresión en la EP. Existen varias escalas que sirven como herramientas para monitorizar cambios a lo largo del tiempo y determinar el efecto de las estrategias terapéuticas en estos pacientes. El abordaje terapéutico se puede enfocar desde el punto de vista farmacológico y no farmacológico. Antidepresivos tricíclicos, inhibidores de la recaptación de serotonina e inhibidores mixtos de serotonina y noradrenalina han demostrado efectividad. También hay reportes positivos de opciones no farmacológicas como la estimulación magnética transcraneal, la terapia cognitiva conductual y la cirugía de estimulación cerebral profunda. Sin embargo, estas últimas requieren más evidencia. La ansiedad se relaciona con empeoramiento de la sintomatología motora y frecuentemente se asocia a síndrome depresivo. Como tratamiento se utilizan habitualmente antidepresivos con perfil ansiolítico y benzodiazepinas. La apatía se asocia con edad avanzada, peor función cognitiva, aumento de los síntomas motores, discapacidad más grave y menor calidad de vida, con una mayor carga para el cuidador.

SUMMARY Non-motor symptoms are frequent in Parkinson's disease (PD), being depression, anxiety and apathy symptoms very prevalent in this population. These symptoms have been shown to be determinants of quality of life in patients with PD, resulting in reduced quality of life, poorer functional status and worse cognitive function, and have been associated with an increase in mortality. Various neurotransmitters systems, such as dopaminergic, serotonergic and noradrenergic pathways, may contribute to the high onset of depression in PD. There are several scales that serve as tools to monitor changes over time and determine the effect of therapeutic strategies in these patients. The therapeutic strategy can be approached from the pharmacological and non-pharmacological point of view. Tricyclic antidepressants, serotonin reuptake inhibitors and mixed serotonin and norepinephrine inhibitors have shown effectiveness. There are also positive reports of non-pharmacological options such as transcranial magnetic stimulation, cognitive behavioral therapy, and deep brain stimulation surgery, however the latter require more evidence. Anxiety is related to worsening of motor symptoms and is frequently associated with depressive symptoms. As a treatment, antidepressants with anxiolytic profile and benzodiazepines are commonly used. Apathy is associated with advanced age, worse cognitive function, increased motor symptoms, more disability and lower quality of life with a greater burden for the caregiver.

Evaluación de la apatía en la enfermedad de Parkinson y escalas disponibles para su medición en la investigación neuropsiquiátrica y la práctica clínica / Evaluation of apathy in Parkinson's disease and available scales for its measurement in neuropsychiatric research and clinical practice

La evaluación de la apatía en patología neuro-psiquiátrica es muy importante en la investigación y en la práctica clínica. Muchas veces sus síntomas son sub-diagnosticados o diagnosticados como depresión y otras condiciones. La presente revisión aborda las escalas más utilizadas las últimas décadas para la valoración de apatía y ofrece recomendaciones y apreciaciones generales sobre su uso y utilidad basada en la bibliografía disponible. Al margen de las diferencias entre escalas la tarea de estandarizar el diagnóstico de apatía en la práctica clínica y la investigación nacionales una necesidad que no debe postergarse al contar con herramientas suficientes y adecuadas a la fecha que han evolucionado desde la definición de Marin hasta la escala Dimensional Apathy Scale (DAS). Se sugiere estudios que validen y adapten culturalmente estas herramientas a nuestro entorno poblacional y pongan en práctica la medición cuantitativa de la apatía en la consulta clínica

The evaluation of apathy in neuropsychiatric pathology is very important in research and in clinical practice. Many times their symptoms are underdiagnosed as part of depression and other conditions. The present review addresses the scales most used in recent decades for the assessment of apathy and offers recommendations and general assessments of their use and utility based on the available literature. Apart from the differences between scales, the task of standardizing the diagnosis of apathy in clinical practice and national research is a need that should not be postponed by having sufficient and appropriate tools to date that have evolved from the definition of Marin to the Dimensional Apathy Scale (DAS). It is suggested that studies validate and culturally adapt these tools to our population environment and put into practice the quantitative measurement of apathy in the clinical environment.

Deep brain stimulation for patients with Parkinson's disease: Effect on caregiver burden. / Influencia de la estimulación cerebral profunda en la carga de cuidadores de pacientes con enfermedad de Parkinson.

INTRODUCTION: Our aim is to assess the burden on caregivers of patients with Parkinson's disease treated with deep brain stimulation (DBS) compared to those caring for patients at advanced stages and undergoing other treatments. We have also assessed the variables associated with presence of caregiver overload. MATERIAL AND METHODS: We included consecutive patients with Parkinson's disease treated with DBS. Our control group included patients in advanced stages of Parkinson's disease undergoing other treatments. Patients were assessed with the following scales: UPDRS-II, UPDRS-III, UPDRS-IV, Hoehn and Yahr, Schwab & England, Barthel, PDQ-39, MoCA, Apathy Evaluation Scale, HADS, and the abbreviated QUIP. Caregiver burden was evaluated with the Zarit caregiver burden interview and their moods were assessed with the HADS scale. RESULTS: We included 11 patients treated with DBS and 11 with other treatments. For patients treated with DBS, we observed a better quality of life according to the PDQ-39 questionnaire (P=.028), and a lower score on the HADS anxiety subscale (P=.010). Caregiver overload was observed in 54.5% of the caregivers of patients in both groups (P=1.000); Zarit scores were similar (P=.835). Caregiver overload was associated with higher scores on the caregiver's Apathy Evaluation Scale (P=.048) and on the HADS anxiety subscale (P=.006). CONCLUSION: According to our results, treatment with DBS is not associated with lower caregiver burden. Apathy in patients and anxiety in caregivers are factors associated with the appearance of overload.

Causas de apatía en parejas casadas y en unión libre / Causes of apathy in married and free union couples

Resumen: El objetivo fue determinar las causas que conducen a la apatía en la pareja haciendo un análisis por sexo. Se trabajó con una muestra no probabilística intencional, compuesta por 150 participantes, igualmente dividida por sexo, quienes reportaron estar casados o vivir en unión libre y tener hijos, de la ciudad de Toluca, México. Se utilizó un cuestionario compuesto por 6 frases incompletas el cual fue validado por jueces expertos con un nivel de acuerdo mayor del 85%. Las aplicaciones fueron individuales en lugares públicos de la ciudad, previa firma del consentimiento informado. Se encontró que las causas que generan apatía en la pareja se deben a la falta de involucramiento, la falta de novedad, la realización de actividades no estimulantes, los conflictos, el cansancio, la falta de atracción sexual y a factores externos. Es interesante señalar que a pesar de reportar apatía y estar sin gusto y con queja muchos permanecen en su relación. Así, el estudio de la apatía puede ser útil para incentivar a las parejas a utilizar estrategias para recuperar el interés dentro de la relación o bien, a decidirse terminar con ésta para buscar la satisfacción de sus necesidades o carencias y alcanzar la paz o el equilibrio personal.

Abstract: The aim of the present investigation was to determine the most common causes that lead to intimate partner apathy analyzing by sex. We worked with a selected sample through a non-probabilistic intentional sampling, composed by 150 participants, equally divided by sex, who reported were married or living in free union and have children, in the city of Toluca, State of Mexico. We used a questionnaire conformed by six open sentences, which was validated by expert's judges with a level of agreement higher than 85%. After obtaining the consent of each participant, the applications were individual in public areas of the city. According to the obtained results, it was found that the most common causes of intimate partner apathy are due to: lack of involvement, lack of novelty, non-stimulating activities, conflicts, tiredness, lack of sexual attraction, and external factors. It is interesting to note that many participants remain with apathy in the relationship because of the fear that represents change, although they live without joy and complaining. Thus, the study of apathy can be useful in the sense of encouraging couples to strategies to regain interest within the relationship or to decide to break up with the couple in order to seek satisfaction of their needs or shortcomings and achieve peace or personal balance.

Tratamiento farmacológico de la apatía en la enfermedad de Parkinson: revisión sistemática de la literatura / Pharmacological Treatment of Apathy in Parkinson's Disease: a Systematic Review of the Literature

Resumen Introducción y objetivos: La apatía, entendida como un déficit para el inicio y el mantenimiento de la acción, es un síntoma que afecta a los pacientes con diversas enfermedades psiquiátricas y neuropsiquiátricas, como demencias, secuelas de traumatismo craneal, esquizofrenia y depresión y enfermedad de Parkinson (EP). La apatía afecta negativamente a la funcionalidad y la calidad de vida de los pacientes con EP y es fuente importante de estrés del cuidador. El tratamiento farmacológico de la apatía en la EP es el foco de esta revisión sistemática. Métodos: Se realizó una búsqueda con selección sistemática de artículos originales sobre el tratamiento de la apatía en la EP en diferentes bases de datos, se consolidaron los resultados, se realizó lectura crítica de los artículos y se discutieron los hallazgos. Resultados: Se incluyeron 11 estudios. Aunque algunos mostraron eficacia, todos presentaban limitaciones metodológicas importantes, que no permitían considerar que se pueda tomar en cuenta los resultados de dichos ensayos clínicos como evidencia para guiar las decisiones clínicas. Conclusiones: Hasta el momento no se puede ofrecer recomendaciones basadas en la evidencia para el tratamiento farmacológico de la apatía en la EP. Hacen falta estudios con mejor calidad metodológica. Es un área de investigación potencialmente fructífera y muy necesaria para los pacientes con EP y sus familiares.

Abstract Introduction and objectives: Apathy, defined as a deficit for initiating and maintaining action, is a symptom affecting patients with diverse psychiatric and neuropsychiatric diseases, including dementia, sequelae of traumatic brain injury, schizophrenia, depression, and Parkinson's disease (PD). Apathy negatively affects function and quality of life of PD patients, and it is an important cause of caregiver's distress. The pharmacological treatment of apathy in PD is the focus of this systematic review. Methods: A comprehensive search and systematic selection was performed in different databases of original research papers on the treatment of apathy in PD. The results were then consolidated, and a critical analysis was made of the research papers. The results are then discussed according to the methodological standards for systematic reviews of the literature. Results: A total of 11 studies were included. Although some studies showed efficacy, all of them had important methodological limitations that hampered the interpretation of results. The results of the examined studies cannot be considered as evidence for guiding clinical decisions. Conclusions: So far, no evidence-based recommendations can be offered for the treatment of apathy in PD. More studies with better methodological quality are needed. It is a potentially fruitful area for research and one badly needed by both PD patients and their caregivers.

[Pharmacological Treatment of Apathy in Parkinson's Disease: a Systematic Review of the Literature]. / Tratamiento farmacológico de la apatía en la enfermedad de Parkinson: revisión sistemática de la literatura.

INTRODUCTION AND OBJECTIVES: Apathy, defined as a deficit for initiating and maintaining action, is a symptom affecting patients with diverse psychiatric and neuropsychiatric diseases, including dementia, sequelae of traumatic brain injury, schizophrenia, depression, and Parkinson's disease (PD). Apathy negatively affects function and quality of life of PD patients, and it is an important cause of caregiver's distress. The pharmacological treatment of apathy in PD is the focus of this systematic review. METHODS: A comprehensive search and systematic selection was performed in different databases of original research papers on the treatment of apathy in PD. The results were then consolidated, and a critical analysis was made of the research papers. The results are then discussed according to the methodological standards for systematic reviews of the literature. RESULTS: A total of 11 studies were included. Although some studies showed efficacy, all of them had important methodological limitations that hampered the interpretation of results. The results of the examined studies cannot be considered as evidence for guiding clinical decisions. CONCLUSIONS: So far, no evidence-based recommendations can be offered for the treatment of apathy in PD. More studies with better methodological quality are needed. It is a potentially fruitful area for research and one badly needed by both PD patients and their caregivers.

Hallazgos morfométricos y funcionales acerca de la ínsula en población VIH+ con apatía / Morphometric and functional findings about the insula in HIV+ population with apathy

La corteza insular es uno de los componentes de la zona paralímbica que presenta conexiones con áreas corticales y subcorticales. El estudio en personas viviendo con VIH (PVVIH), donde la apatía es frecuente, la implicó como modulador de respuesta emocional y ejecutiva. El objetivo es describir morfométricamente y funcionalmente la ínsula en relación con estructuras cerebrales corticales y subcorticales en PVVIH con apatía en comparación con controles y con PVVIH sin apatía, a fin de determinar su implicancia. Estudiamos 23 encéfalos de PVVIH de sexo masculino con apatía según evaluaciones neuropsiquiátricas. Se utilizó resonancia magnética (RM) con protocolo cognitivo para cuantificación y tomografía por emisión de fotón único (SPECT) para evaluar la perfusión cortical, aplicados a: cortezas frontales, insulares, núcleos caudados y cuerpos amigdalinos. Registramos reducción significativa morfométrica de la corteza del cíngulo anterior izquierdo, núcleo caudado ipsilateral y cortezas dorso-laterales en VIH+ con apatía; la ínsula anterior registró una reducción no significativa (p=0,4). En el análisis funcional se determinó hipoperfusión en las cortezas del cíngulo anterior izquierdo, insular anterior izquierda y en el caudado de forma asimétrica; con hipoperfusiones relativas en regiones del hemisferio derecho. La perfusión de la ínsula anterior izquierda fue correlativa con la del caudado ipsilateral y proporcional a la severidad en el test de apatía. Concluimos que en la cohorte evaluada de pacientes viviendo con VIH y apatía hallamos un significativo compromiso funcional de la corteza insular anterior, correlativo con la afectación funcional y morfométrica de los núcleos caudados. La implicancia de la corteza insular sugiere su participación en la psicopatología de la apatía, parámetro vinculado con el déficit de interés por las actividades e iniciativas.

The insular cortex is one of the components of the paralimbic zone that has connections with cortical and subcortical areas. The study in people living with HIV (PLHIV), in which apathy is frequent, implicated the structure as a modulator of emotional and executive responses. The objective is to make a description based on morphometry and functionality of the insula in relation to cortical and subcortical structures in PLHIV with apathy compared to controls and compared to PLHIV without apathy, in order to determine its implication. We studied 23 brains of male PLHIV with apathy according to neuropsychiatric evaluations. Magnetic resonance imaging (MRI) with cognitive quantification protocol and Single photon emission tomography (SPECT) to evaluate cortical perfusion were used applied to: frontal cortices, insular cortex, caudate nuclei and amygdaloid bodies. We recorded a significant morphometric reduction of the left anterior cingulate cortex, left caudate nucleus and dorso-lateral cortex in PLHIV with apathy; anterior insula cortex recorded a non-significant reduction (p = 0.4). Functional analysis showed hypoperfusion in the left anterior cingulum cortex, left anterior insular region and caudate nucleus´s perfusion were assymetrically; relative hypoperfusion were found in right hemisphere regions. The perfusion of the left anterior insula was correlated with ipsilateral caudate and proportional to the severity in the apathy test. We concluded in the cohort evaluated patients living with HIV and apathy found a significant functional compromise of the anterior insular cortex, correlated with morphometric and functional impairment of the caudate nuclei. The implication of the insular cortex suggests their participation in the psychopathology of apathy, parameter linked with the deficit of interest in the activities and initiatives.

The perception of apathy by caregivers of patients with dementia in Parkinson's disease / A percepção da apatia pelos cuidadores de pacientes com demência na doença de Parkinson

ABSTRACT Background: Apathy is one of the main neuropsychiatric symptoms in patients with Parkinson's disease (PD) and is associated with Parkinson's disease dementia (PDD). Objective: To identify the characteristics of apathy in individuals with PDD according to caregiver perception. Methods: Thirty-nine patients with PD according to MDS criteria for PDD were included. The following scales were used: the Hoehn and Yahr, the Unified Parkinson's Disease Rating Scale III, Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Apathy Evaluation Scale (AES). Results: A total of 97.4% of the patients showed results consistent with apathy. Analysis of question 14 of the AES revealed no correlation with the total result of all the questions [r=-1293, r²=0.0167, 95%CI (-0.4274 to 0.1940), P=0.2162], however, there was a correlation of responses to the same question with depression data on the MADRS scale [r=-0.5213, r²=0.2718, 95%CI (-0.7186 to -0.2464), P=0.00033]. Conclusion: Apathy is a disorder associated with PDD. However, the scoring scheme of the AES questions can lead to different interpretations of caregiver responses, highlighting limitations of the tool for use in studies of PDD.

RESUMO Embasamento: A apatia é uma das principais manifestações neuropsiquiátricas dos pacientes com doença de Parkinson (DP) e está associada com a demência da doença de Parkinson (DDP). Objetivo: Identificar as características da apatia em indivíduos com DDP através impressão dos cuidadores. Metodos: Foram avaliados 39 pacientes com DP de acordo com os critérios da MDS para DDP. Foram usadas as escalas de Hoehn e Yahr, Unified Parkinson's Disease Rating Scale III, Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), Escala de Depressão de Montgomery-Asberg (MADSR) e Escala de Avaliação de Apatia (AES). Resultados: 97,4% dos pacientes apresentaram resultados condizentes com apatia. Analisando-se a questão 14 da AES, não foi encontrado correlação com o resultado total de todas as questões [r=-1293, r²=0,0167, 95%IC (-0.4274 a 0.1940), P=0,2162], porém, houve uma correlação das respostas da mesma questão com os dados de depressão pela escala MADSR [r=-0.5213, r²=0.2718, 95%IC (-0.7186 a -0.2464), P=0.00033]. Conclusão: A apatia é um distúrbio relacionado com a DDP. Entretanto, a forma de pontuação das questões da AES pode induzir a diferentes interpretações das respostas dos cuidadores levando-se a um questionamento sobre a limitação da ferramenta para estudos em DPP.