Disease-specific profiles of apathy in Alzheimer's disease and behavioural-variant frontotemporal dementia differ across the disease course.

Apathy is one of the most prevalent and disabling non-cognitive symptoms of dementia. This loss of motivation and pervasive decline in goal-directed behaviour represents a core diagnostic feature of behavioural-variant frontotemporal dementia (bvFTD) and is also common in Alzheimer's disease (AD). However, despite growing recognition of a multidimensional model, apathy has typically been examined as a unitary symptom. Here, we employed a cross-sectional design to characterise the multidimensional nature of apathy across syndromes and disease course. 92 participants (44 bvFTD, 20 AD, 28 controls) completed the Dimensional Apathy Scale (DAS) to quantify emotional, executive, and initiation apathy. Patients were divided into early and late stages based on time since symptom onset. All participants underwent structural MRI and voxel-based morphometry was used to identify neural correlates of apathy dimensions. In the early stage of the disease (< 5 years since onset), emotional apathy was greater in bvFTD than AD. In contrast, in the late stage (> 5 years since onset), executive apathy was greater in AD than bvFTD, although apathy was elevated across all dimensions compared to controls. Notably, apathy was observed in the absence of self-reported depression in 46.2% of patients, with no patients classified as depressed only. Neuroimaging analyses revealed both common and divergent prefrontal and subcortical neural correlates associated with apathy dimensions. Our results reveal differing profiles of apathy across the disease course, in AD and bvFTD, with distinct brain regions mediating these dimensions. These findings will inform the development of appropriate treatment targets to ameliorate the impact of apathy in dementia.

IRT Analysis of the Frontal Systems Behavior Scale: Identifying the Best Items for Use with Geriatric Patients in Primary Care.

OBJECTIVE: The Frontal Systems Behavior Scale (FrSBe) (Grace & Malloy, 2001) assesses behavioral dysfunction associated with frontal-subcortical damage; it is often used to measure these indicators of executive dysfunction in older adults with possible dementia. Although prior research supports the FrSBe's clinical utility and factorial validity, little attempt has been made to examine which items are most useful for geriatric cases. The goal of the present study is to identify these items. METHOD: Data from 304 older patients referred for neuropsychological assessment were used to examine the FrSBe's three subscales: Apathy (A; 14 items), Executive Dysfunction (E; 17 items), and Disinhibition (D; 15 items). Item properties were investigated using the Graded Response Model, a two-parameter polytomous item response theory model. RESULTS: Difficulty parameters, discrimination parameters, and information curves identified 18 items that effectively discriminate (a ≥ 1.70) between levels of behavioral dysfunction and measure a range of dysfunction (bA: -1.23 - 2.22; bD: -.29 - 2.14; bE: -1.81 - 1.77). CONCLUSIONS: Most FrSBe items were effective at discriminating various levels of behavioral dysfunction, though weaker items were identified. CLINICAL IMPLICATIONS: The findings suggest the FrSBe is a useful clinical tool when working with a geriatric population, though some items provide more information than others.

Distinct Subtypes of Apathy Revealed by the Apathy Motivation Index.

Apathy is a debilitating but poorly understood disorder characterized by a reduction in motivation. As well as being associated with several brain disorders, apathy is also prevalent in varying degrees in healthy people. Whilst many tools have been developed to assess levels of apathy in clinical disorders, surprisingly there are no measures of apathy suitable for healthy people. Moreover, although apathy is commonly comorbid with symptoms of depression, anhedonia and fatigue, how and why these symptoms are associated is unclear. Here we developed the Apathy-Motivation Index (AMI), a brief self-report index of apathy and motivation. Using exploratory factor analysis (in a sample of 505 people), and then confirmatory analysis (in a different set of 479 individuals), we identified subtypes of apathy in behavioural, social and emotional domains. Latent profile analyses showed four different profiles of apathy that were associated with varying levels of depression, anhedonia and fatigue. The AMI is a novel and reliable measure of individual differences in apathy and might provide a useful means of probing different mechanisms underlying sub-clinical lack of motivation in otherwise healthy individuals. Moreover, associations between apathy and comorbid states may be reflective of problems in different emotional, social and behavioural domains.

Las terapias de intervención cognitiva en el tratamiento de los trastornos de conducta en la enfermedad de Alzheimer. Evidencias sobre su eficacia y correlaciones neurobiológicas / Cognitive intervention therapy as treatment for behaviour disorders in Alzheimer disease: Evidence on efficacy and neurobiological correlations

Introducción: Los síntomas conductuales y psicológicos (SCP) son muy prevalentes en la enfermedad de Alzheimer (EA) presentándose en más del 90% de los pacientes a lo largo del curso de la enfermedad. Los SCP disminuyen la calidad de vida, tanto del paciente, como de sus cuidadores, al tiempo que incrementan los costes asistenciales. Son los principales responsables de la carga que experimentan los cuidadores, favoreciendo la institucionalización prematura de los pacientes. Desarrollo: En la actualidad existe consenso en considerar más eficaces aquellos modelos de intervención que combinan los tratamientos farmacológicos y los no farmacológicos para personas con EA. En varios estudios se ha comprobado la eficacia de los fármacos anticolinesterásicos y de la memantina combinados con terapias de intervención cognitiva (TIC), para mejorar el funcionamiento cognitivo y la capacidad funcional de los pacientes en el desempeno de las actividades de la vida diaria. Sin embargo, la eficacia de las TIC sobre los SCP no está aun claramente establecida, lo que ha limitado su aplicación con esta finalidad en la práctica clínica. El objetivo de esta revisión es el de recoger la información disponible acerca de la eficacia de las TIC en el tratamiento de los SCP en los pacientes con EA. Conclusiones: Los resultados de esta revisión sugieren que las TIC puede tener efectos beneficiosos sobre los SCP de la EA, por lo que debería ser considerada como una opción terapéutica para el abordaje de los mismos

Introduction: The prevalence of behavioural and psychological symptoms (BPS) is very high among patients with Alzheimer disease (AD); more than 90% of AD patients will present suchsymptoms during the course of the disease. These symptoms result in poorer quality of life for both patients and caregivers and increased healthcare costs. BPS are the main factors involved in increases to the caregiver burden, and they often precipitate the admission of patients to residential care centres. Development: Current consensus holds that intervention models combining pharmacological and non-pharmacological treatments are the most effective for AD patients. Several studies have shown cholinesterase inhibitors and memantine combined with cognitive intervention therapy (CIT) to be effective for improving patients’ cognitive function and functional capacity for undertaking daily life activities. However, the efficacy of CIT as a treatment for BPS has not yet been clearly established, which limits its use for this purpose in clinical practice. The objective of this review is to gather available evidence on the efficacy of cognitive intervention therapy (CIT) on BPS in patients with AD. Conclusions: The results of this review suggest that CIT may have a beneficial effect on BPS in patients with AD and should therefore be considered a treatment option for patients with AD and BPS

Apathy and dementia. Nosology, assessment and management.

Apathy, characterized by lack of motivation and loss of initiative, is a non-cognitive symptom that affects a high proportion, but not all, of patients with all forms of dementia. To explore the phenomenon of apathy in people with dementia, we searched the PubMed and Google Scholar electronic databases for original research and review articles on apathetic behaviors in patients with dementia using the search terms "apathy, behavioral and psychological symptoms, dementia, Alzheimer's disease, Frontotemporal dementia, Dementia associated with Parkinson's disease, Huntington's disease, Vascular dementia". Some nosological aspects, neurobiological basis, and assessment of, as well as, potential benefits of non-pharmacologic and pharmacologic interventions for apathy in dementia are discussed. Greater understanding of apathy will improve the identification, intervention, and treatment of this ubiquitous and pernicious syndrome.

[Apathy in the structure of mental and neurological disorders of the old age].

The studies on apathy, a common phenomenon in psychiatry, are summarized. The definitions of this term suggested by different authors are presented. The difference between apathy as a symptom and apathy as a syndrome is described. Main pathogenetic mechanisms of the development and epidemiology of this disorder, the results on the differential diagnosis of apathy and depression in patients with neurological and mental diseases as well as methods of treatment are presented.

Developing concepts in negative symptoms: primary vs secondary and apathy vs expression.

Negative symptoms in schizophrenia, such as blunted affect, alogia, asociality, anhedonia, and avolition, remain challenging to treat in many patients, but new concepts may lead to a better understanding of the definition and treatment of these symptoms. The most widely used rating scales for negative symptoms (the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale) were developed in the 1980s, but more recent findings, such as insight into aspects of anhedonia, have led to the creation of new rating scales (the Clinical Assessment Interview for Negative Symptoms and the Brief Negative Symptom Scale). Clinicians should differentiate between primary and secondary negative symptoms in order to select the best treatment option. Secondary negative symptoms may be caused by comorbid conditions, psychotic symptoms, medication side effects, and substance abuse. On most rating scales, negative symptoms have also been found to load onto 1 of 2 domains, apathy/anhedonia/asociality or diminished expression (blunted affect and alogia). This distinction may facilitate the development of new treatments.

The Brazilian version of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity in dementia.

BACKGROUND: Patients with dementia may be unable to describe their symptoms, and caregivers frequently suffer emotional burden that can interfere with judgment of the patient's behavior. The Neuropsychiatric Inventory-Clinician rating scale (NPI-C) was therefore developed as a comprehensive and versatile instrument to assess and accurately measure neuropsychiatric symptoms (NPS) in dementia, thereby using information from caregiver and patient interviews, and any other relevant available data. The present study is a follow-up to the original, cross-national NPI-C validation, evaluating the reliability and concurrent validity of the NPI-C in quantifying psychopathological symptoms in dementia in a large Brazilian cohort. METHODS: Two blinded raters evaluated 312 participants (156 patient-knowledgeable informant dyads) using the NPI-C for a total of 624 observations in five Brazilian centers. Inter-rater reliability was determined through intraclass correlation coefficients for the NPI-C domains and the traditional NPI. Convergent validity included correlations of specific domains of the NPI-C with the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Index (CMAI), the Cornell Scale for Depression in Dementia (CSDD), and the Apathy Inventory (AI). RESULTS: Inter-rater reliability was strong for all NPI-C domains. There were high correlations between NPI-C/delusions and BPRS, NPI-C/apathy-indifference with the AI, NPI-C/depression-dysphoria with the CSDD, NPI-C/agitation with the CMAI, and NPI-C/aggression with the CMAI. There was moderate correlation between the NPI-C/aberrant vocalizations and CMAI and the NPI-C/hallucinations with the BPRS. CONCLUSION: The NPI-C is a comprehensive tool that provides accurate measurement of NPS in dementia with high concurrent validity and inter-rater reliability in the Brazilian setting. In addition to universal assessment, the NPI-C can be completed by individual domains.

Abordaje terapéutico de los síntomas no motores de la enfermedad de Parkinson / Therapeutic management of the non-motor symptoms in Parkinson's disease

Introducción. La enfermedad de Parkinson (EP) es una entidad compleja con una sintomatología diversa que presenta, además de los clásicos síntomas motores, un amplio número de síntomas no motores. Estos síntomas son muy prevalentes desde el inicio de la enfermedad e incluso pueden preceder en el tiempo a los síntomas motores (estreñimiento, alteración del olfato, trastorno de conducta del sueño REM) actuando como marcadores precoces de la enfermedad. Causan importante impacto en la calidad de vida de los enfermos con EP. Pueden ser los síntomas más incapacitantes para el paciente. Por todo ello, precisan de un manejo adecuado que mejore el bienestar de nuestros pacientes. Objetivo. Dar una visión actualizada del tratamiento de los síntomas no motores más prevalentes de la EP. Desarrollo. Se describen los síntomas no motores (vegetativos, trastornos del sueño, apatía) más prevalentes y discapacitantes de la enfermedad de Parkinson y se hace una revisión actualizada de su tratamiento. Conclusión: La alteración que la enfermedad produce en otros sistemas distintos al dopaminérgico causa un amplio número de síntomas distintos a los motores. Su mejor conocimiento permitirá diagnosticar y optimizar el tratamiento de estos síntomas, reforzando el bienestar de nuestros pacientes (AU)

Introduction. Parkinson's disease (PD) is a complex condition with a variety of symptoms, including a large number of nonmotor symptoms, in addition to the classic motor symptoms. These symptoms are highly prevalent from the onset of the disease and may even appear earlier than the motor symptoms (constipation, altered sense of smell, REM sleep behaviour disorder) and act as early markers of the disease. They have a significant impact on the quality of life of patients with PD and can be the most disabling symptoms for the patient. As a result, they need adequate management that improves our patients’ welfare. Aims. The objective of this study is to offer an updated view of the most prevalent non-motor symptoms of PD. Development. We describe the most prevalent and disabling non-motor symptoms (vegetative, sleep disorders, apathy) of Parkinson's disease and we also conduct a review of the state-of-the-art in its treatment. Conclusions. The alterations that the illness produces in systems other than the dopaminergic system cause a large number of symptoms in addition to the motor ones. A better understanding of them will make it possible to diagnose and optimise the treatment of these symptoms, thereby boosting our patients' welfare (AU)

The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages). METHODS: Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity. RESULTS: Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains. CONCLUSION: Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies.

Apatía en la enfermedad de Parkinson / Apathy in Parkinson's disease

Introducción: La apatía es un síndrome comportamental por disfunción del proceso que origina los actos inducidos por estímulos externos o los propios. Es muy frecuente en la enfermedad de Parkinson, con una prevalencia que oscila en el 16-48%. Actualmente se aceptan tres subtipos diferentes de apatía con un correlato anatómico-funcional distinto en cado uno de los casos: cognitiva, emocional y por déficit en la autoactivación. Cada uno de estos subtipos está implicado en un grado variable en la apatía de la enfermedad de Parkinson. El diagnóstico es fundamentalmente clínico apoyado en escalas neuropsicológicas. La evaluación de la apatía debe hacerse simultáneamente con la de la depresión y el deterioro cognitivo. Conclusiones: La apatía es un síntoma muy importante y de reciente consideración a tener muy en cuenta en los pacientes con enfermedad de Parkinson por la repercusión en la calidad de vida del paciente. Es importante el diagnóstico diferencial con la depresión y el deterioro cognitivo, pues el abordaje terapéutico es diferente. Para ello es necesario incluir en los protocolos de exploración escalas específicas para valorar este síntoma (AU)

Introduction: Apathy is a behavioural syndrome due to dysfunction of the process that gives rise to actions induced by external or personal stimuli. Apathy is very common in Parkinson’s disease, with a prevalence that ranges between 16-48%. Three subtypes of apathy are currently accepted, which are anatomically and functionally different: cognitive, emotional and due to a deficit in auto-activation. Each of these subtypes is involved to a variable degree in the apathy of Parkinson’s disease. The diagnosis is desupported by clinical, diagnostic and neuropsychological tests. The evaluation of the apathy must be done simultaneously along with with depression cognitive deficit. Conclusions: Apathy has become a very important symptom to bear in mind in Parkinson’s disease patients as it has significant repercussions on the quality of life of the patient. It is very important to do a differential diagnosis with the depression and the cognitive deficit since the therapeutic approach is different. Specific scales to measure this symptom should be included in the evaluation protocols of cognitive function in Parkinson’s disease (AU)