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Introduction: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning. Methods: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI. Results: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects. Discussion: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.
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In old age, the chronic use of substances such as alcohol and sedatives, and more recently opioids, is a major public health and personal problem. Despite this, relatively little attention has been paid to the disorders associated with the use of these substances. These recommendations have been formulated by the Swiss Society for Elderly Psychiatry and Psychotherapy (SPPA) in collaboration with the Swiss Nurses' Association (SNA) and the Swiss Society for Addiction Medicine (SSAM). They provide a summary of the knowledge about addiction disorders in old age for the benefit of those working with patients, with the aim of strengthening prevention, early detection and appropriate interventions.
À l'âge avancé, la consommation chronique de substances comme l'alcool et les sédatifs, et plus récemment les opioïdes, représente un important problème pour les personnes concernées et de santé publique. Malgré cela, relativement peu d'attention a été accordée aux troubles associés à la consommation de ces substances. Les présentes recommandations ont été formulées par la Société suisse de psychiatrie et psychothérapie de la personne âgée (SPPA) en collaboration avec l'Association suisse des infirmières et infirmiers (ASI) et la Société suisse de médecine de l'addiction (SSMA). Elles mettent à la disposition des intervenants auprès des patients un résumé des connaissances au sujet des troubles addictifs à l'âge avancé, avec comme objectif de renforcer la prévention et le dépistage précoce, et des interventions adaptées.
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Medicina do Vício , Comportamento Aditivo , Idoso , Analgésicos Opioides , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/prevenção & controle , Humanos , Hipnóticos e Sedativos , PsicoterapiaRESUMO
Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly Abstract. Psychotic disorders in the elderly cover a wide range of causes and manifestations. They often occur as part of a depression, dementia, substance abuse or delirium. While psychosis can occur with a first manifestation in advanced age, many patients with chronic psychotic disorders reach a high age. Many elderly individuals are also affected by cognitive impairment and somatic conditions, making a third-party history most relevant. The associated changes in life and the complexity of the individual situation needs to be integrated into the diagnosis and treatment. The presented recommendations have been developed under the lead of the Swiss Society of Old Age Psychiatry (SGAP) in collaboration with the Swiss Association of Nurses (SBK) and the subcommittees for gerontological and psychiatric nursing of the association of nursing science (VFP) as well as further professional societies. We aim to make current knowledge concerning diagnosis and treatment available to the interprofessional teams working in in- and outpatients' settings.
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Geriatria , Transtornos Psicóticos , Transtornos Relacionados ao Uso de Substâncias , Idoso , Humanos , Pacientes Ambulatoriais , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/terapiaRESUMO
BACKGROUND: Mental-somatic multimorbidity in general hospital settings is associated with long hospital stays, frequent rehospitalization, and a deterioration of disease course, thus, highlighting the need for treating hospital patients more holistically. However, there are several challenges to overcome to address mental health conditions in these settings. This study investigated hospital personnel's perceived importance of and experiences with mental-somatic multimorbidities of patients in hospital settings in Basel, Switzerland, with special consideration of the differences between physicians and nurses. METHODS: Eighteen semi-structured interviews were conducted with nurses (n = 10) and physicians (n = 8) in different hospitals located in Basel, Switzerland. An inductive approach of the framework analysis was used to develop the themes. RESULTS: Four themes emerged from the data analysis: 1) the relevance of mental-somatic multimorbidity within general hospitals, 2) health professionals managing their emotions towards mental health, 3) knowledge and competencies in treating patients with mental-somatic multimorbidity, and 4) interprofessional collaboration for handling mental-somatic multimorbidity in hospital settings.The mental-somatic multimorbidities in general hospital patients was found to be relevant among all hospital professionals, although the priority of mental health was higher for nurses than for physicians. This might have resulted from different working environments or in efficient interprofessional collaboration in general hospitals. Physicians and nurses both highlighted the difficulties of dealing with stigma, a lack of knowledge of mental disorders, the emphasis place on treating somatic disorders, and competing priorities and work availability, which all hindered the adequate handling of mental-somatic multimorbidity in general hospitals. CONCLUSION: To support health professionals to integrate mental health into their work, proper environments within general hospitals are needed, such as private rooms in which to communicate with patients. In addition, changes in curriculums and continuing training are needed to improve the understanding of mental-somatic multimorbidities and reduce negative stereotypes. Similarly, interprofessional collaboration between health professionals needs to be strengthened to adequately identify and treat mentally multimorbid patients. A stronger focus should be placed on physicians to improve their competencies in considering patient mental health in their daily somatic treatment care.
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Hospitais Gerais , Multimorbidade , Humanos , Recursos Humanos em Hospital , Pesquisa Qualitativa , SuíçaRESUMO
Recommendations for the Prevention, Diagnostics and Therapy of Addiction Disorders in the Elderly Abstract. Although the chronic consumption of alcohol and sedatives, and increasingly opioids, represents a major problem in old age with consequential damage for those affected, little attention has been paid to the substance abuse disorders in old age. The aim of the present recommendations, a collaboration work of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP), Swiss Nurses Association (SBK) and Swiss Society of Addiction Medicine (SSAM), is to summarize the current state of knowledge in prevention, diagnostics and therapy of substance abuse disorders in old age for an interprofessional clinical team. They are intended to help strengthen prevention and early diagnosis, and consciously emphasize psychotherapy and nursing intervention options.
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Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Idoso , Benzodiazepinas , Humanos , Psicoterapia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
Decision-making capacity (DMC) in aging adults has become increasingly salient as the number of older adults, life expectancy, and the amount of wealth to be transferred from older generations have all increased. The accurate and reliable determination of older adults' DMC is a particularly important topic given its implication in legal, financial, and health decisions. Based upon the four-ability DMC model promulgated by Appelbaum and Grisso in the 1980's, a number of MacArthur Competence Assessment Tools have been developed and widely utilized. However, these tools do not include cognitive testing or other sources of objective data and have limited validity in a medico-legal setting, necessitating additional options for the evaluation of DMC. This is significant from the perspective of the patient because they have a vested interest in accurate and objective assessment of their DMC across domains.Given the disparities in the assessment of DMC, the authors propose, through this debate article, that the evaluation of DMC in the aging adult population utilize a combination of traditional interview and domain specific instruments and neuropsychological testing. To achieve a consensus on the issue, medical experts in a number of fields related to capacity evaluation, including psychiatry, neurology, neuropsychology, and general medicine were consulted and recruited as authors. Experts in Swiss law and ethics were also consulted and provided input.A tendency to focus on a single capacity, and in particular, the ability to consent to medical treatment, arose in the literature. Similarly, there are many instruments purporting to evaluate a single capacity (e.g., consenting to medical treatment, managing finances), while other areas important to the evaluation of DMC received little attention (e.g., activities of daily living, the ability to live independently, to marry, to resist undue influence, and to make a will or advanced care directive). Medical and legal experts in the multidisciplinary group agreed that there is a clear need for more consistency across evaluation of DMC domains and that a combined approach of traditional methods and neuropsychological testing provides a more thorough evaluation and better serves the patient.
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Atividades Cotidianas , Tomada de Decisões , Idoso , Envelhecimento , Humanos , Competência Mental , Testes Neuropsicológicos , Encaminhamento e ConsultaRESUMO
In October 2019, a Swiss panel of experts met for the Dementia Summit in Brunnen, Switzerland, to discuss the latest scientific findings on basic and clinical research, as well as practical and political approaches to the challenges of dementia disorders in Switzerland. Here, we present the conference summary. To study pathophysiological changes, as well as the underlying mechanism of fluid biomarker changes, excellent experimental approaches, including transgenic mouse models, are available. Current knowledge about presymptomatic disease progression is largely derived from the longitudinal study of individuals with autosomal dominant mutations (Dominantly Inherited Alzheimer Network). Importantly, more than one third of identified dementia risk factors can be modified. For example, sleep disturbances are not only associated with dementia and neurodegeneration in specific brain regions, but also precede cognitive decline and contribute to the development of brain pathology. Regarding the neuropsychological examination of dementia disorders, standardised tests of social cognition, one of the six cognitive domains that must be assessed according to the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders, are missing, but now under development. The most important new therapeutic approach in the treatment of Alzheimer’s disease is the current attempt to prevent β-amyloid accumulation. While until now clinical studies have failed because of side effects or insufficient clinical effectiveness, Biogen recently announced positive results of high doses of aducanumab, a monoclonal antibody against β-amyloid. Other approaches also show promise. In China, sodium oligomannate has been approved to treat Alzheimer's disease. The substance suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Assistive technologies for dementia patients can help identify relevant information for care and nursing, as well as measurements for clinical interventions. Dementia patients have a high risk of developing delirium, even in the home environment. Therefore, it is necessary to use and further develop multi-disciplinary and systematic detection and prevention strategies. Homecare models for dementia patients with multidisciplinary teams have been established and evaluated and should be expanded. Dementia is the third-leading cause of death in Switzerland. In palliative care for severe dementia, the improvement of quality of life is of primary importance. The goals of the National Dementia Strategy, to increase the quality of life in those affected and to reduce taboos surrounding the disease, are still unrealised. The need for further national and regional engagement in order to implement the different findings of the strategy has largely been acknowledged, and these implementations have become the core tasks of a national dementia platform.
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Doença de Alzheimer , Demência , Animais , Humanos , Estudos Longitudinais , Camundongos , Qualidade de Vida , SuíçaRESUMO
The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer's disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents' retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD.
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Doença de Alzheimer/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Rememoração Mental/fisiologia , Idoso , Doença de Alzheimer/psicologia , Feminino , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória Episódica , Testes Neuropsicológicos , Tamanho do Órgão/fisiologiaRESUMO
Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and health-care-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyper- and hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when non-pharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.
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Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Delírio/tratamento farmacológico , Cuidados Paliativos/métodos , Idoso , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
The literature describes a basic neurofunctional antagonism between episodic memory encoding and retrieval with opposed patterns of neural activation and deactivation, particularly in posterior midline regions. This has been coined the encoding/retrieval (E/R) flip. The present fMRI study uses an innovative task paradigm to further elucidate neurofunctional relations of encoding and retrieval in associative memory. Thereby, memory encoding is implemented as implicit (non-deliberate) cognitive process, whereas the prior literature focused mainly on explicit encoding. Moreover, instead of defining brain activations related to successful (vs. unsuccessful) memory performance, the task paradigm provides proper no-memory baseline conditions. More specifically, the encoding task includes trials with non-contingent (not learnable) stimulus combinations, while the retrieval task uses trials with a simple matching exercise with no mnemonic requirements. The analyses revealed circumscribed activation in the posterior middle cingulate cortex (pMCC) together with prominent deactivation in the anterior insula cortex (aIC) as core neural substrate of implicit memory encoding. Thereby, the pMCC exhibited positive functional connectivity to the hippocampus. Memory retrieval was related to an activation pattern exactly opposed to memory encoding with deactivation in the pMCC and activation in the aIC, while the aIC additionally exhibited a negative (i.e., arguably inhibitive) functional connectivity to the pMCC. Important to note, the observed pattern of activations/de-activations in the pMCC appears to conflict with prevalent E/R flip findings. The outlined results and their (alleged) discrepancies with prior study reports are discussed primarily in the context of the default mode network's functioning and its context-sensitive regulation. Finally, we point out the relevance of the present work for the understanding and further investigation of the neurofunctional aberrations occurring during normal and pathological aging.
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OBJECTIVES: Since the advent of imaging techniques, the role of the neuropsychological assessment has changed. Questions concerning everyday functionality became primarily important and, thus, ecologically valid neuropsychological assessments are mandatory. Virtual reality (VR) environments might provide a way of implementing immersive cognitive assessments with a higher degree of everyday-life-related cognitive demands. METHOD: We report on a VR-based episodic memory examination in N = 30 young and N = 18 healthy older adults (HOA) using a kitchen scene. The test procedure was designed to be structurally comparable to clinically used California Verbal Learning Test (CVLT) in terms of repeated learning trials as well as short and long delayed recall measures. RESULTS: The results showed that age-related learning and performance decrements were mainly evident in the CVLT but not in the VR-memory examination. CONCLUSIONS: The ecologically valid VR-memory examination might provide a more accurate "age-fair" estimation of everyday-life-related memory demands in HOA than the frequently and clinically used CVLT. We concluded this from our finding of context-related automatic and effortless activations of deeply experience based encoding and retrieval strategies with regard to everyday-life-related objects in the HOA, which might not be paralleled by learning arbitrary word associations. (PsycINFO Database Record
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Envelhecimento/fisiologia , Transtornos da Memória/fisiopatologia , Memória Episódica , Testes Neuropsicológicos/normas , Aprendizagem Verbal/fisiologia , Realidade Virtual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Transtorno Depressivo/diagnóstico , Transtorno Depressivo/terapia , Idoso , Antidepressivos/uso terapêutico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/terapia , Terapia Combinada , Transtorno Depressivo/classificação , Transtorno Depressivo/psicologia , Diagnóstico Diferencial , Medicina Baseada em Evidências , Fidelidade a Diretrizes , Humanos , Classificação Internacional de Doenças , Psicoterapia , Fatores de Risco , Suicídio/psicologia , Prevenção do SuicídioRESUMO
OBJECTIVE: Misdiagnosis of early behavioral variant frontotemporal dementia (bvFTD) with major depressive disorder (MDD) is not uncommon due to overlapping symptoms. The aim of this study was to improve the discrimination between these disorders using a novel facial emotion perception task. METHOD: In this prospective cohort study (July 2013-March 2016), we compared 25 patients meeting Rascovsky diagnostic criteria for bvFTD, 20 patients meeting DSM-IV criteria for MDD, 21 patients meeting McKhann diagnostic criteria for Alzheimer's disease dementia, and 31 healthy participants on a novel emotion intensity rating task comprising morphed low-intensity facial stimuli. Participants were asked to rate the intensity of morphed faces on the congruent basic emotion (eg, rating on sadness when sad face is shown) and on the 5 incongruent basic emotions (eg, rating on each of the other basic emotions when sad face is shown). RESULTS: While bvFTD patients underrated congruent emotions (P < .01), they also overrated incongruent emotions (P < .001), resulting in confusion of facial emotions. In contrast, MDD patients overrated congruent negative facial emotions (P < .001), but not incongruent facial emotions. Accordingly, ratings of congruent and incongruent emotions highly discriminated between bvFTD and MDD patients, ranging from area under the curve (AUC) = 93% to AUC = 98%. Further, an almost complete discrimination (AUC = 99%) was achieved by contrasting the 2 rating types. In contrast, Alzheimer's disease dementia patients perceived emotions similarly to healthy participants, indicating no impact of cognitive impairment on rating scores. CONCLUSIONS: Our congruent and incongruent facial emotion intensity rating task allows a detailed assessment of facial emotion perception in patient populations. By using this simple task, we achieved an almost complete discrimination between bvFTD and MDD, potentially helping improve the diagnostic certainty in early bvFTD.
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Transtorno Depressivo Maior/diagnóstico , Expressão Facial , Demência Frontotemporal/diagnóstico , Reconhecimento Psicológico , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Estudos de Casos e Controles , Transtorno Depressivo Maior/psicologia , Diagnóstico Diferencial , Feminino , Demência Frontotemporal/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Estudos ProspectivosRESUMO
Alzheimer's disease - State of the art, and emerging diagnostics and therapeutics Abstract. Alzheimer's disease (AD) constitutes the most prevalent neurodegenerative disorder, and the most frequent cause of dementia. Current diagnostics include a clinical examination, brain imaging, as well as laboratory testing in order to exclude other treatable disorders. Depending on the findings constellation a lumbar puncture with determination of amyloid-ß-, tau- and phospho-tau-proteins, PET imaging and if necessary further investigations are performed. Acetylcholineesteraseinhibitors as well as the NMDA-antagonist mematine allow symptomatic treatment of AD. The development of novel curative drugs is now showing considerable progress. After initially frustrating results, immunotherapies addressing amyloid-ß pathology are now showing first positive effects when administered early in the disease course. First immunotherapies targeting tau pathology are furthermore reaching phase 2 and 3 trials, after hints of positive clinical effects in phase 1 trials. An additional set of more than 70 trials investigates non-immune mediated treatment strategies. Diagnostic advances include the development of amyloid-PET imaging, where after the amyloid-ß-PET, tau-PET imaging is now reaching clinical implementation. In parallel to the technical advances in cerebrospinal fluid diagnostics, first blood-based biomarkers for AD are being developed.
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Doença de Alzheimer , Peptídeos beta-Amiloides/antagonistas & inibidores , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Humanos , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
BACKGROUND: Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects. METHODS: Seventy-five patients with probable AD, 96 individuals with MCI, and 53 age-matched and sex-matched healthy control subjects were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-terminus, C-terminus, and full-length BACE1. RESULTS: Compared with healthy control subjects, plasma BACE1 activity (Vmax) significantly increased by 53.2% in subjects with MCI and by 68.9% in patients with probable AD. Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD. CONCLUSIONS: Plasma BACE1 activity is significantly increased in MCI converters and patients with probable AD. The sensitivities and specificities of BACE1 activity for the patients were 84% and 88%, respectively. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.
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Doença de Alzheimer/sangue , Secretases da Proteína Precursora do Amiloide/sangue , Ácido Aspártico Endopeptidases/sangue , Disfunção Cognitiva/sangue , Progressão da Doença , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Disfunção Cognitiva/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Sintomas Prodrômicos , Prognóstico , Sensibilidade e EspecificidadeRESUMO
Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field.
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Envelhecimento , Demência , Depressão , Demência/classificação , Demência/diagnóstico , Demência/terapia , Depressão/classificação , Depressão/diagnóstico , Depressão/terapia , Diagnóstico Diferencial , Humanos , Neuroimagem , Testes NeuropsicológicosRESUMO
Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.
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Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/psicologia , Biomarcadores/sangue , Disfunção Cognitiva/psicologia , HumanosRESUMO
OBJECTIVE: Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. DESIGN AND PARTICIPANTS: The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. MEASUREMENTS AND RESULTS: Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. CONCLUSIONS: By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD.
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Transtorno Depressivo Maior/psicologia , Expressão Facial , Demência Frontotemporal/psicologia , Percepção Social , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Demência Frontotemporal/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Alzheimer's disease (AD) is characterized by memory disturbances primarily caused by pathogenic mechanisms affecting medial temporal lobe structures. As proposed by current theories of memory formation, this decrease is mediated by the age of the acquired knowledge. However, they cannot fully explain specific patterns of retrograde amnesia in AD. In the current study we examined an alternative approach and investigated whether the extent and severity of retrograde amnesia in AD is mediated by the frequency of memory retrieval or whether it depends on the mere age of knowledge. We compared recall of autobiographical incidents from three life periods in patients with amnestic mild cognitive impairment (aMCI), patients with early dementia of Alzheimer type (eDAT), and healthy control (HC) individuals using the Autobiographical Memory Interview. Retrieval frequency was operationalized by a paired comparison analysis. In contrast to HC individuals, recall of autobiographical incidents was impaired in patients with aMCI and eDAT following Ribot's gradient, with a reduced memory loss for remote compared to more recent life events. However, there was a strong effect of retrieval frequency on memory performance with frequently retrieved incidents memorized in more detail than less frequently retrieved episodes. Remote memories were recalled more often than recent ones. These findings suggest that more frequently retrieved autobiographical memories generally become more independent of the hippocampal complex and might thus be better protected against early hippocampal damage related to AD. Hence, the extent of retrograde amnesia in AD appears mainly mediated by the frequency of memory retrieval, which could plausibly explain why cognitive activity can effectively delay the onset of memory decline in AD.
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Doença de Alzheimer/psicologia , Memória Episódica , Rememoração Mental , Idoso , Estudos de Casos e Controles , Disfunção Cognitiva/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Testes Neuropsicológicos , Inquéritos e QuestionáriosRESUMO
Suicide rates are highest among the elderly in Switzerland. The estimated number of unreported cases is particularly high in this age group. The risk factors are multidimensional, including depression and social isolation. The detection and management of the controllable risk factors, foremost depression, is of particular importance for suicide prevention. Old age depression often shows an atypical presentation, is misinterpreted as a normal process of aging and is not adequately treated.