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.

A resting-state functional MRI study on amplitude of low-frequency fluctuation and functional connectivity alteration of parkinson′s disease with apathy / 中华放射学杂志

Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.

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.

Risk Factors of Apathy in Parkinson's Disease / 中国康复理论与实践

Objective:To study the prevalence and related factors of apathy in patients with Parkinson's disease (PD)． Methods:From November, 2017 to December, 2019, 254 PD patients in our hospital were included. According to Starkstein Apathy Scale (SAS), they were divided into apathy group and non-apathy group. Clinical data such as demographic data, motor symptoms, non-motor symptoms and motor complications were collected for comparison between two groups. Logistic regression analysis was performed to investigate the risk factors of apathy in PD. Results:Among 254 PD patients, 124 (48.8%) cases were in apathy. Compared with non-apathy group, apathy group was older in age and age of onset, higher in the scores of Movement Disorder Society United Parkinson's Disease Rating Scale part III (MDS-UPDRS Ⅲ), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Pittsburgh Sleep Quality Index (PSQI) (t > 2.291, P < 0.05), and lower in the scores of Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) (t > 22.424, P < 0.001). There was no statistically significant difference in gender, time of education, body mass index (BMI), disease course, Hoehn-Yahr (H-Y) stage, wearing-off phenomenon, dyskinesia, on-and-off phenomenon, and the scores of Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDQ) and Epworth Sleeping Scale (ESS) between two groups (P > 0.05). Logistic regression analysis showed that the age of disease onset, MoCA and HAMD scores were correlated with apathy in patients with PD (P < 0.05). Conclusion:The presence of apathy in PD may be associated with older age of disease onset, severity of depression and cognitive impairment.

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.

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.

Apathy syndrome in a patient previously treated with selective serotonin reuptake inhibitors for depression / 영남의대학술지

There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.

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.

Clinical characteristics of early Parkinson′ s disease patients with emotional apathy and its relationship with other non?motor symptoms / 中国综合临床

Objective To observe the characteristics of apathy in early Parkinson′s disease patients,analyze its relationship with other non?motor symptoms, and explore its impact on the quality of life.Methods Clinical data of 75 patients with Parkinson′s disease admitted to xingtai people′s hospital from August 2014 to August 2017 were selected.Unified Parkinson′s disease rating scale?III(UPDRS?III ), Modified apathy rating scale ( MAES ), Montgomy?asberg Depression rating scale ( MADRS ) and Simple mental state test ( MMSE) were used to evaluate patients′ motor symptoms, indifference, depression and cognitive function.The relationship between apathy and other non?motor symptoms was analyzed by Parkinson′s disease non?motor symptom evaluation scale.Parkinson′s disease questionnaire?39 ( PDQ?39) was used to evaluate the quality of life.The patients were divided into the affective indifference group and the non?affective indifference group according to whether the patients were accompanied by affective indifference.Results 21.3%( 16／75) of the patients were diagnosed with apathy.Emotional indifference group UPDRS score ?Ⅲ(23.98±9.46),not apathy group(14.74±6.27).There was significant difference between the two groups (P＜0.001).MMSE score of the indifferent group was ( 21.26±3.21),and that of the non?indifferent group was (26.57± 3.42).There was significant difference between the two groups ( P＝0.038).PDQ?39 score of the emotionally indifferent group was (65.20± 25.78),which was significantly higher than that of the non?emotionally indifferent group ( 34.86± 25.42).There was significant difference between the two groups (P＜0.001).In the comparison of Parkinson′s disease non?motor symptom evaluation scale,the fatigue symptom score of the emotionally indifferent group was (6.1±0.2) significantly higher than that of the non?indifferent group (2.3±0.7),and the difference was statistically significant (P＝0.006).The score of lack of interest was ( 4.8 ± 1.5) in the indifferent group and ( 1.3 ± 0.8) in the non?indifferent group.The difference between the two groups was statistically significant (P＝0.017).Conclusion Apathy has a high incidence in early Parkinson′s disease patients,often combined with fatigue and lack of interest symptoms.It has a serious impact on the quality of daily life in the future.

Anxiety and depression like behaviors in chronic Parkinsonism of cynomolgus monkey / 中华行为医学与脑科学杂志

Objective To establish and evaluate anxiety and depression like behaviors in MPTP-in-duced chronic Parkinsonism cynomolgus monkey. Methods Ten cynomolgus monkeys ( 15. 0 ± 1. 5 years old) were divided into normal group and MPTP-induced parkinsonism group(PD group),5 animals in each group. The behavioral methods for evaluating the anxiety and depression like behaviors in non-human prima-tes included Apathy Feeding Test (AFT),Human Intruder Test (HIT),Novel Fruit Test (NFT) and Preda-tor Confrontation Test (PCT). The changes in behavioral indicators between the two groups were analyzed. Results In AFT,PD group spent more time in observing food on both sides,and significantly higher than that in normal group (left:0. 73(0. 49) s,0. 50(0. 28) s,P<0. 01;right:0. 75(0. 60) s,0. 53(0. 16) s,P<0. 01),moreover PD group had limb disorder on the right side,and spent more time in taking food which sig-nificantly more than normal group (0. 83(0. 20) s,0. 57(0. 14) s,P<0. 01). In HIT,PD group moved and stood better than that in normal group,and occurred abnormal behaviors,such as climbed,grinded,scratched and shook cages (P>0. 05),while normal group spent more time in the back of cage during Stare and Back period( Stare:0(64. 70)s,111. 27(38. 94)s,P=0. 033; Back:0(25. 84) s,120(114. 69) s; H=17. 397). Finally,PD group had lower take-up rate and higher withdrawal rate than normal group in PCT(P>0. 05). Conclusion This study establishes a multi-angle evaluation of behavioral methods for anxiety and depres-sion in non-human primates. The analysis confirmed that chronic Parkinson's disease cynomolgus monkeys has different degrees of anxiety and depression,which provides a new method for preclinical intervention in Parkinson's disease.

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.

Brain Perfusion Correlates of Apathy in Alzheimer's Disease

BACKGROUND AND PURPOSE: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy. METHODS: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed. RESULTS: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p < 0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β = −0.25; p = 0.04). CONCLUSIONS: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients.

A comparison of the Lille Apathy Rating Scale-informant, the Apathy Evaluation Scale-Informant, and the Neuropsychiatric Inventory-Apathy Subscale in mild cognitive impairment informants / 中华神经科杂志

Objective To compare the Lille Apathy Rating Scale-informant (LARS-i),the Apathy Evaluation Scale-Informant (AES-I) and the Neuropsychiatric Inventory-Apathy Subscale (NPI-Apathy) in mild cognitive impairment (MCI) informants.Methods Data were collected from 181 informants of patients with MCI by the LARS-i,AES-I and NPI-Apathy scales.The evaluation results by the three scaleswere analyzed by correlation analysis and receiver operating characteristic (ROC) curve.Results By the Chinese versions of the LARS-i and AES-I scales,the best ROC curve was at a cutoff score of-16,33 respectively for a prediction of apathy (with sensitivity of 72.00％,75.31％ respectively,and specificity of 65.38％,75.76％ respectively).The scores of the LARS-i and AES-i scales (r =0.566,P ＜0.01),and the scores of AES-I and NPI-Apathy scales (r =0.388,P ＜ 0.01) were positively correlated.The AES-I and NPI-Apathy scores were positively correlated with the scores of the Geriatric Depression Scale (r =0.250,0.169,P＜0.05),while the score of the LARS-i scale not.The scores of LARS-i,AES-I scales were negatively correlated with the score of MoCA scale (r =-0.232,-0.239,P ＜ 0.01),whereas the NPI-Apathy score had no correlation with the MoCA score.The AES-I and LARS-i scales reported greater apathy compared to that reported by the NPI-Apathy scale,with cases of 94,81,25 respectively.Conclusions The results of the Chinese versions of LARS-i and AES-I scales are similar,which are better than the NPI-Apathy scale in MCI informants in China.And the LARS-i scale can distinguish between apathy and depression to a certain extent.

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.

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.

Clinical research of dementia with behavioral and psychological symptoms / 实用医学杂志

Objective To discuss the clinical features of behavioral and psychological symptoms of demen-tia(BPSD)and the relation between different sub-clinical syndromes and cognition. Methods One hundred and sixteen dementia patients were assessed with neuropsychiatric inventory and mini-mental state examination (MMSE)and made factor analysis according to DSM-IV-R. Results Twelve common behavioral and psychological symptoms could be further divided into five sub-syndromes,including disinhibition behavior,psychosis,agitation, emotion and apathy factors. MMSE total score and years of education entered regression equation of apathy factor (P<0.05). Conclusion BPSD can be divided into five factors and apathy factor are related with cognitive function.

Advances in Research on the Apathy of the Subthalamic Nucleus-deep Brain Stimulation / 现代生物医学进展

Parkinson's disease is characterized by progressive motor dysfunction owing to degeneration of dopaminergic neurons in the substantia nigra and other nuclei.Recently,the bilateral high frequency stimulation of the subthalamic nucleus deep brain stimula tion (STN-DBS) as the treatment of PD was famous with good curative effect.But postoperative apathy as its side-effect impact on the therapeutic effect and the quality of life of patients seriously,which drawn the attention of clinicians.In this article,we summarized the incidence,manifestation and treatment of postoperative apathy and tried to provide some ideas for clinicians.