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.

Embotional Blunting or apathy by SSRI? A sistematic review about their emotional effects / ¿Apatía o embotamiento emocional por ISRS? Una revisión de la literatura.

Introduction: Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that have revolutionized the psychopharmacological therapeutic field since their appearance. They are in the first line of recommendation for the treatment of anxiety disorders and major depressive disorder. And although they are better tolerated and have a better side effect profile than the classic ones, they are not exempt from them. Among the adverse effects of SSRIs little considered by health professionals, are apathy or mental dullness. Restrictions of the range of emotions that are related to normal life, such as the ability to cry or feel pleasure, have been reported. This phenomenon has been called variously in the literature, such as emotional blunting, apathy, emotional indifference, or decreased sensitivity or emotional response. Objectives: The aim of this review is to analyze the emotional effects of SSRI that are described in the literature. Methods: A bibliographic review of the literature published in Pubmed from 2006 to 2021 was carried out, with the words Mesh "SSRI" and "Apathy" and "emotional blunting". Results: Literature reports indicate that the mental dullness produced by SSRIs is generated in at least 50 % of the patients who receive them, with different intensities between them. Conclusions: Although effects of emotional blunting or apathy have been reported with various groups of antidepressants, all reports agree that it occurs more frequently in patients taking SSRIs than with other antidepressants.

Introducción: Los Inhibidores Selectivos de la Recaptación de Serotonina (ISRS) son un grupo de antidepresivos que revolucionaron desde su surgimiento, el campo de la terapéutica psicofarmacológica, y se encuentran en la primera línea de recomendación para el tratamiento de los trastornos de ansiedad y del trastorno depresivo mayor. Si bien son mejor tolerados y presentan un mejor perfil de efectos adversos que los clásicos, no están exentos de ellos. Dentro de los efectos adversos de los ISRS poco considerados por los profesionales de la salud, se encuentran la apatía o el embotamiento mental. Se han reportado en la literatura restricciones del rango de las emociones que están relacionadas con la vida normal, como la capacidad de llorar o de sentir placer. Este fenómeno ha sido designado de varias maneras, como embotamiento emocional, apatía, indiferencia emocional,  disminución de sensibilidad o de la respuesta emocional. Objetivos: El objetivo del trabajo es analizar los efectos a nivel emocional de los ISRS, descriptos en la literatura. Metodología: Se realizó una revisión bibliográfica de la literatura publicada en Pubmed desde 2006 hasta 2021, con las palabras Mesh "SSRI" and "Apathy" and  "emotional blunting". Resultados: Según reportes de la literatura, el embotamiento emocional producido por los ISRS se genera en al menos un 50 % de los pacientes que lo reciben, con diferentes intensidades entre ellos. Conclusión: Si bien se han reportado efectos de embotamiento emocional o apatía con varios grupos de antidepresivos, todos los reportes concuerdan que se produce con más frecuencia en pacientes medicados con ISRS que con otros antidepresivos.

Are all antidepressants the same? The consumer has a point.

BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.

White Matter Hyperintensities and Poststroke Apathy: A Fully Automated MRI Segmentation Study.

INTRODUCTION: Poststroke apathy (PSA) is a common neuropsychiatric disorder that may affect up to 30% of stroke patients. Despite the difficulties of investigating this condition (overlapping with depression, heterogeneity of diagnostic criteria, a small number of studies), some recent diffusion tensor imaging studies have suggested that widespread microstructural white matter (WM) disruption plays a key role in the development of PSA. Therefore, we intended to investigate this hypothesis by evaluating the relationship between WM hyperintensities (WMH) and apathy in patients with cerebrovascular disease. METHODS: We studied patients with apathy (n = 7), depression (n = 13), comorbid apathy and depression (n = 13), and controls (n = 20), and we investigated the variables associated with the volume of WMH measured by an automated brain MRI segmentation software. RESULTS: The overall prevalence of PSA was 37.7% (pure and comorbid). Patients with apathy presented a higher volume of WMH in comparison to controls. Mini-Mental State Examination (MMSE), NPI-A, and the number of cerebral microbleeds were the only variables associated with WMH. Conversely, NPI-D did not correlate to WMH. DISCUSSION/CONCLUSION: This is an exploratory study that supports the view of PSA as a distinct syndrome from PSD mediated mainly by diffuse white matter hyperintensities, which suggests that WM disruption is an important pathway to the development of apathy in stroke patients.

Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder.

Patients with epilepsy can experience different neuropsychiatric symptoms related (peri-ictal) or not (interictal) with seizures. Peri-ictal symptoms can precede (pre-ictal) or follow (post-ictal) the seizure, or even be the expression of the seizure activity (ictal). Neuropsychiatric symptoms, such as irritability and apathy, are among the most frequent pre-ictal manifestations. Ictal fear is reported by around 10% of patients with focal seizures, and sometimes can be difficult to differentiate from panic attacks. Post-ictal anxiety, mood and psychotic symptoms are also frequently reported by patients. Peri-ictal phenomena can occur as isolated symptom or as a cluster of symptoms, sometimes resembling a full-blown psychiatric syndrome. Actually, peri-ictal and interictal neuropsychiatric manifestations seem to be closely associated.

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.

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.

A case of developmental pedophilia unmasked by frontotemporal dementia.

A 65-year-old right-handed man gradually became socially indifferent and less active. Four years later, he was indicted for molesting children on multiple occasions. Psychomotor slowness and executive impairment contrasted with sparing of language, semantic memory, visuospatial perception, construction praxis, and right-left orientation. Neuroimaging showed asymmetric atrophy of dorsomedial frontal and anterior temporal lobes, and hypoperfusion of medial prefrontal cortex consistent with a diagnosis of behavioral variant of frontotemporal dementia. Further information revealed that the patient exhibited pedophilic behavior several years prior to symptom onset. We conclude that preexisting developmental pedophilia was "unmasked" by the underlying progressive frontotemporal degeneration.

Apathy, Executive Function, and Emotion Recognition Are the Main Drivers of Functional Impairment in Behavioral Variant of Frontotemporal Dementia.

Background: The cognitive and neuropsychiatric deficits present in patients with behavioral variant frontotemporal dementia (bvFTD) are associated with loss of functionality in the activities of daily living (ADLs). The main purpose of this study was to examine and explore the association between the cognitive and neuropsychiatric features that might prompt functional impairment of basic, instrumental, and advanced ADL domains in patients with bvFTD. Methods: A retrospective cross-sectional study was conducted with 27 patients with bvFTD in its early stage (<2 years of evolution) and 32 healthy control subjects. A neuropsychological assessment was carried out wherein measures of cognitive function and neuropsychiatric symptoms were obtained. The informant-report Technology-Activities of Daily Living Questionnaire was used to assess the percentage of functional impairment in the different ADL domains. To identify the best determinants, three separate multiple regression analyses were performed, considering each functional impairment as the dependent variable and executive function, emotion recognition, disinhibition, and apathy as independent variables. Results: For the basic ADLs, a model that explains 28.2% of the variability was found, in which the presence of apathy (ß = 0.33, p = 0.02) and disinhibition (ß = 0.29, p = 0.04) were significant factors. Concerning instrumental ADLs, the model produced accounted for 63.7% of the functional variability, with the presence of apathy (ß = 0.71, p < 0.001), deficits in executive function (ß = -0.36, p = 0.002), and lack of emotion recognition (ß = 0.28, p = 0.017) as the main contributors. Finally, in terms of advanced ADLs, the model found explained 52.6% of the variance, wherein only the presence of apathy acted as a significant factor (ß = 0.59, p < 0.001). Conclusions: The results of this study show the prominent and transverse effect of apathy in the loss of functionality throughout all the ADL domains. Apart from that, this is the first study that shows that the factors associated with loss of functionality differ according to the functional domain in patients with bvFTD in its early stage. Finally, no other study has analyzed the impact of the lack of emotion recognition in the functionality of ADLs. These results could guide the planning of tailored interventions that might enhance everyday activities and the improvement of quality of life.

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.

Insula and Amygdala Atrophy Are Associated With Functional Impairment in Subjects With Presbycusis.

Hearing loss is an important risk factor for dementia. However, the mechanisms that relate these disorders are still unknown. As a proxy of this relationship, we studied the structural brain changes associated with functional impairment in activities of daily living in subjects with age related hearing loss, or presbycusis. One hundred eleven independent, non-demented subjects older than 65 years recruited in the ANDES cohort were evaluated using a combined approach including (i) audiological tests: hearing thresholds and cochlear function measured by pure tone averages and the distortion product otoacoustic emissions respectively; (ii) behavioral variables: cognitive, neuropsychiatric, and functional impairment in activities of daily living measured by validated questionnaires; and (iii) structural brain imaging-assessed by magnetic resonance imaging at 3 Tesla. The mean age of the recruited subjects (69 females) was 73.95 ± 5.47 years (mean ± SD) with an average educational level of 9.44 ± 4.2 years of schooling. According to the audiometric hearing thresholds and presence of otoacoustic emissions, we studied three groups: controls with normal hearing (n = 36), presbycusis with preserved cochlear function (n = 33), and presbycusis with cochlear dysfunction (n = 38). We found a significant association (R 2 D = 0.17) between the number of detected otoacoustic emissions and apathy symptoms. The presbycusis with cochlear dysfunction group had worse performance than controls in global cognition, language and executive functions, and severe apathy symptoms than the other groups. The neuropsychiatric symptoms and language deficits were the main determinants of functional impairment in both groups of subjects with presbycusis. Atrophy of insula, amygdala, and other temporal areas were related with functional impairment, apathy, and language deficits in the presbycusis with cochlear dysfunction group. We conclude that (i) the neuropsychiatric symptoms had a major effect on functional loss in subjects with presbycusis, (ii) cochlear dysfunction is relevant for the association between hearing loss and behavioral impairment, and (iii) atrophy of the insula and amygdala among other temporal areas are related with hearing loss and behavioral impairment.

Can Social Cognition Measurements Differentiate Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease Regardless of Apathy?

BACKGROUND: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) share cognitive and behavioral symptoms, such as apathy. Social cognition measurements are useful in distinguishing bvFTD from AD, but their accuracies may be affected by apathy. OBJECTIVE: To investigate whether social cognition measurements can distinguish bvFTD from either apathetic or non-apathetic AD patients. METHODS: Three groups of participants were enrolled in the present study: bvFTD (n = 22), AD (n = 20), and healthy controls (HC, n = 23). The AD group was divided into apathetic (n = 10) and non-apathetic (n = 10). All subjects underwent comprehensive neuropsychological examination, including the short version of the Social and Emotional Assessment (Mini-SEA), which comprises the facial emotion recognition test and the faux-pas recognition test (Faux-Pas Test). Apathy was assessed according to the Starkstein's Apathy (SA) Scale. RESULTS: The bvFTD and AD groups did not differ on global cognitive efficiency and on executive functions. In comparison to the whole AD group, bvFTD displayed lower Faux-Pas Test and Mini-SEA scores. Both AD subgroups, apathetic or non-apathetic, exhibited similar performance on all social cognition measurements. In comparison to either apathetic AD or non-apathetic AD, bvFTD patients underperformed on the Faux-Pas Test and on the Mini-SEA. The area under the curve values for the Mini-SEA total score were 0.87 (bvFTD versus AD), 0.90 (bvFTD versus apathetic AD), and 0.83 (bvFTD versus non-apathetic AD). CONCLUSION: Social cognition tests provide accurate distinction between bvFTD against either apathetic AD or non-apathetic AD. Social cognition measurements did not correlate with apathy severity.

Apathy in frontotemporal dementia is related to medial prefrontal atrophy and is independent of executive dysfunction.

INTRODUCTION: Apathy is the most common neuropsychiatric syndrome in behavioral variant frontotemporal dementia (bvFTD), and encompasses cognitive, behavioral and affective symptoms. The neural basis of apathy in bvFTD is not completely understood. Previous neuroimaging studies have poorly considered executive impairment and dementia severity as possible confounding factors. Herein we investigated the neural basis of apathy in bvFTD through structural neuroimaging taking into account these factors. METHODS: We included patients with probable bvFTD (n = 21) and cognitively healthy controls (HC, n = 22). Participants were matched for age, sex and schooling. All subjects underwent a thorough neuropsychological examination, including tests for executive functions and social cognition. Apathy was assessed with the Starkstein Apathy Scale (SAS). All subjects underwent 3T brain MRI. We investigated correlations between SAS scores and gray matter atrophy within the bvFTD group. Executive function (Frontal Assessment Battery) and disease severity were considered as covariates in neuroimaging analyses. RESULTS: Compared to HC, bvFTD patients had lower scores on global cognitive efficiency, executive functions and social cognition. All bvFTD had clinically relevant apathy (scores greater than 14 in the SAS). Performance in executive function tests did not correlate with apathy scores. The severity of apathy was negatively correlated with gray matter volumes in midline prefrontal regions, namely orbitofrontal cortex and both anterior and dorsal regions of cingulate cortex. CONCLUSIONS: Apathy in bvFTD is related to a specific network of prefrontal cortical areas critically involved in effort-based behavior for rewards and appears to be independent of executive dysfunction.

Amnestic and non-amnestic symptoms of dementia: An international study of Alzheimer's disease in people with Down's syndrome.

The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. OBJECTIVE: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. METHODS: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. RESULTS: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). CONCLUSION: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.

Neuropsychiatric symptoms and executive function impairments in Alzheimer's disease and vascular dementia: The role of subcortical circuits.

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.

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.

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.

The Prevalence and Correlation of Non-motor Symptoms in Adult Patients with Idiopathic Focal or Segmental Dystonia.

Background: Idiopathic focal dystonia is a motor syndrome associated with dysfunction of basal ganglia circuits. Observations have suggested that many other non-motor symptoms may also be part of the clinical picture. The aim was to assess the prevalence and correlation of non-motor symptoms in patients with common idiopathic focal or segmental dystonia. Methods: In a single-center cross-sectional case-control study, we evaluated the presence of pain, neuropsychiatric symptoms, and sleep alterations in 28 patients with blepharospasm, 28 patients with cervical dystonia, 24 patients with writer's cramp, and 80 control subjects matched for sex, age, and schooling. We obtained clinical and demographic data, and evaluated patients using the Fahn-Marsden Dystonia Rating Scale and other specific scales for dystonia. All subjects completed the following questionnaires: Beck Depression Inventory, Beck Anxiety Inventory, Social Phobia Inventory, Apathy Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Brief Pain Scale, and the World Health Organization Quality of Life brief scale. Results: The patients presented more symptoms of depression, anxiety, and apathy than the control subjects. They also reported worse quality of sleep and more pain complaints. Patients with blepharospasm were the most symptomatic subgroup. The patients had worse quality of life, and the presence of pain and symptoms of apathy and depression were the main influences for these findings, but not the severity of motor symptoms. Discussion: Patients with dystonia, especially those with blepharospasm, showed higher prevalence of symptoms of depression, anxiety, apathy, worse quality of sleep, and pain. These symptoms had a negative impact on their quality of life.

Neuropsychiatric Symptoms in Alzheimer's Disease Are the Main Determinants of Functional Impairment in Advanced Everyday Activities.

BACKGROUND: Neuropsychiatric symptoms and cognitive impairment are independent contributors of functional impairment in activities of daily living (ADL) in Alzheimer's disease (AD) patients. ADL could be divided according to its complexity in three subdomains: basic (BADL), instrumental (IADL), and advanced (a-ADL). OBJECTIVE: Studying the cognitive and neuropsychiatric determinants of BADL, IADL, and a-ADL in normal cognitive elders and AD patients. METHODS: 144 subjects were graduated using the clinical dementia rating (CDR) in CDR = 0, n = 52 (control group) and 92 AD patients CDR = 0.5, n = 34 and CDR = 1&2, n = 58. They were assessed with measures of cognitive performance and neuropsychiatric symptoms that were included in regression models to measure the best predictors for each ADL subdomain at every CDR status. RESULTS: AD patients were significantly older, and had significantly more severe functional impairment, neuropsychiatric symptoms, and cognitive decline than controls. The best predictors of functional impairment in controls and CDR = 0.5 AD patients were neuropsychiatric symptoms; in the CDR 0.5 patients, apathy severity was the most important determinant of IADL and a-ADL impairment. While in the CDR 1&2 AD patients, cognitive impairment was the principal determinant of functional impairment, being memory the best determinant of IADL and a-ADL impairment, while global cognition was of BADL impairment. CONCLUSIONS: The contribution of cognitive impairment and neuropsychiatric symptoms varied according to the subdomain of ADL, and the CDR. In very mild AD and controls the neuropsychiatric symptoms are the best predictors of more complex ADL impairment, while cognitive impairment is more important at mild to moderate states of AD.