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Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.

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AIM: To explore associations of cerebrospinal fluid biomarkers of neurodegeneration and amyloidosis with caregiver burden, cognition and functionality in dementia with Lewy bodies (DLB) paired with late-onset Alzheimer's disease (AD) and healthy older people. METHODS: Consecutive outpatients with DLB were matched with outpatients with AD according to sex, cognitive scores and dementia stage, and with cognitively healthy controls according to age and sex to investigate associations of cerebrospinal fluid amyloid-ß (Aß42,Aß40,Aß38), tau, phospho-tau Thr181, ubiquitin, α-synuclein and neurofilament light with caregiver burden, functionality, reverse digit span, a clock drawing test, Mini-Mental State Examination (MMSE) and Severe MMSE, adjusted for sex, age, education, dementia duration and APOE-ε4 alleles. RESULTS: Overall, 27 patients with DLB (78.98 ± 9.0 years-old; eleven APOE-ε4 +) were paired with 27 patients with AD (81.50 ± 5.8 years-old; twelve APOE-ε4 +) and 27 controls (78.98 ± 8.7 years-old; four APOE-ε4 +); two-thirds were women. In AD, Aß42/Aß38 and Aß42 were lower, while tau/Aß42 and phospho-tau Thr181/Aß42 were higher; α-synuclein/Aß42 was lower in DLB and higher in AD. The following corrected associations remained significant: in DLB, instrumental functionality was inversely associated with tau/phospho-tau Thr181 and tau/Aß42, and reverse digit span associated with α-synuclein; in AD, instrumental functionality was inversely associated with neurofilament light, clock drawing test scores inversely associated with phospho-tau Thr181/Aß42 and α-synuclein/Aß42, and Severe MMSE inversely associated with tau/Aß42 and tau/phospho-tau Thr181. CONCLUSIONS: Cerebrospinal fluid phospho-tau Thr181 in DLB was similar to AD, but not Aß42. In associations with test scores, biomarker ratios were superior to isolated biomarkers, while worse functionality was associated with axonal degeneration only in AD.

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BACKGROUND: Early differentiation between Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) is important for accurate prognosis, as DLB patients typically show faster disease progression. Cortical neural networks, necessary for human cognitive function, may be disrupted differently in DLB and AD patients, allowing diagnostic differentiation between AD and DLB. OBJECTIVE: This proof-of-concept study assessed whether the application of machine learning techniques to data derived from resting-state electroencephalographic (rsEEG) rhythms (discriminant sensor power, 19 electrodes) and source connectivity (between five cortical regions of interest) allowed differentiation between DLB and AD. METHODS: Clinical, demographic, and rsEEG datasets from DLB patients (N=30), AD patients (N=30), and control seniors (NOld, N=30), matched for age, sex, and education, were taken from our international database. Individual (delta, theta, alpha) and fixed (beta) rsEEG frequency bands were included. The rsEEG features for the classification task were computed at both sensor and source levels. The source level was based on eLORETA freeware toolboxes for estimating cortical source activity and linear lagged connectivity. Fluctuations of rsEEG recordings (band-pass waveform envelopes of each EEG rhythm) were also computed at both sensor and source levels. After blind feature reduction, rsEEG features served as input to support vector machine (SVM) classifiers. Discrimination of individuals from the three groups was measured with standard performance metrics (accuracy, sensitivity, and specificity). RESULTS: The trained SVM two-class classifiers showed classification accuracies of 97.6% for NOld vs. AD, 99.7% for NOld vs. DLB, and 97.8% for AD vs. DLB. Three-class classifiers (AD vs. DLB vs. NOld) showed classification accuracy of 94.79%. CONCLUSION: These promising preliminary results should encourage future prospective and longitudinal cross-validation studies using higher resolution EEG techniques and harmonized clinical procedures to enable the clinical application of these machine learning techniques.

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BACKGROUND: Behavioral features may reflect proteinopathies predicting pathophysiology in neurodegenerative diseases. OBJECTIVE: We aimed to investigate associations of cerebrospinal fluid biomarkers of amyloidogenesis and neurodegeneration with neuropsychiatric features in dementia with Lewy bodies (DLB) compared with late-onset Alzheimer's disease (AD) and cognitively healthy people. METHODS: Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive scores, and with cognitively healthy controls according to sex and age to investigate associations of cerebrospinal fluid amyloid-ß (Aß)42, Aß40, Aß38, total tau, phospho-tau Thr181, α-synuclein, ubiquitin, and neurofilament light with neuropsychiatric features according to APOEɛ4 carrier status. RESULTS: Overall, 27 patients with DLB (78.48±9.0 years old, eleven APOEɛ4 carriers) were paired with 27 patients with AD (81.00±5.8 years old, twelve APOEɛ4 carriers) and 27 controls (78.48±8.7 years old, four APOEɛ4 carriers); two thirds were women. Behavioral burden was more intense in DLB. Biomarker ratios reflecting amyloidogenesis and neurodegeneration in DLB were more similar to those in AD when patients carried APOEɛ4 alleles. After corrections for false discovery rates, the following associations remained significant: in DLB, dysphoria was associated with tauopathy and indirect measures of amyloidogenesis, while in AD, agitation, and night-time behavior disturbances were associated with tauopathy, and delusions were associated with tauopathy and indirect measures of amyloidogenesis. CONCLUSION: Biomarker ratios were superior to Aß and tau biomarkers predicting neuropsychiatric symptoms when associations with isolated biomarkers were not significant. At the end, APOEɛ4 carrier status influenced amyloidogenesis and tau pathology in DLB and in AD, and axonal degeneration only in DLB.

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Abstract Background Lewy body dementia (LBD) impairs performance in daily activities and affects motor, language and visuospatial tasks. Objective We aimed to correlate neuropsychiatric and motor assessments with language and visual organization tests in LBD. Methods Twenty-two patients with dementia with Lewy bodies and ten patients with Parkinson's disease dementia participated on a cross-sectional study that assessed cognition, functionality, caregiver burden, verbal fluency, the primer-level dictation section of the Boston Diagnostic Aphasia Examination (PLD-BDAE), the Hooper Visual Organization Test, the Neuropsychiatric Inventory and the Movement Disorder Society - Unified Parkinson's Disease Rating Scale. Results Language and visuospatial test results followed motor impairment and general cognitive performance. Whereas visual organization did not predict performance in the PLD-BDAE, visuospatial abilities and verbal fluency were concurrently associated, suggesting that linguistic impairment in LBD may be attributed to neuropsychological components of cognition and language. Only visual organization was associated with behaviour, suggesting that neuropsychiatric symptoms associate with differential impairment of visual organization in comparison with language in LBD. Schooling did not affect visual organization or language test performance, while the length of dementia was negatively associated with visual organization and verbal fluency. Discussion Though visual organization tests follow behaviour and motor performance in LBD, there is differential impairment regarding language skills.

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Ekbom Syndrome, also known as parasitosis delusion or psychogenic parasitosis, is a rare condition in which patients present with a fixed belief of being infested by parasites, vermin or small insects, along with tactile hallucinations (such as pruritus or sensations of the parasites crawling over or under the skin). The syndrome may occur idiopathically or be associated with other medical conditions and drug use. This case report describes the occurrence of Ekbom syndrome in a patient diagnosed with Lewy Body Dementia (LBD), a neurodegenerative disease that commonly presents with sensory perception and thought disorders and other neuropsychiatric symptoms. Although visual hallucination is considered a core diagnostic criterion, other modalities of psychiatric symptoms can also occur posing a further challenge for correct diagnosis. Proper recognition allows early diagnosis and adequate treatment, preventing hazardous antipsychotic use in these patients.

A síndrome de Ekbom, também conhecida como delírio parasitário ou parasitose psicogênica, é uma condição rara na qual os pacientes apresentam crença fixa de estarem infestados por parasitas, vermes ou insetos, acompanhada de alucinações táteis (como prurido ou sensação dos parasitas andando sobre ou sob a pele). A síndrome pode ocorrer de forma idiopática ou associada a outras condições médicas ou uso de drogas. Este relato de caso descreve a ocorrência da síndrome de Ekbom em um paciente diagnosticado com Demência com corpos de Lewy (DCL), uma doença degenerativa que comumente se apresenta com desordens de sensopercepção e pensamento, e outros sintomas neuropsiquiátricos. A alucinação visual é considerada um dos critérios diagnósticos nucleares, entretanto outras modalidades de sintomas psiquiátricos podem ocorrer criando desafios adicionais ao diagnóstico correto. O reconhecimento apropriado permite o diagnóstico precoce e tratamento adequado, prevenindo o uso arriscado de antipsicóticos nesses pacientes.

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ABSTRACT Ekbom Syndrome, also known as parasitosis delusion or psychogenic parasitosis, is a rare condition in which patients present with a fixed belief of being infested by parasites, vermin or small insects, along with tactile hallucinations (such as pruritus or sensations of the parasites crawling over or under the skin). The syndrome may occur idiopathically or be associated with other medical conditions and drug use. This case report describes the occurrence of Ekbom syndrome in a patient diagnosed with Lewy Body Dementia (LBD), a neurodegenerative disease that commonly presents with sensory perception and thought disorders and other neuropsychiatric symptoms. Although visual hallucination is considered a core diagnostic criterion, other modalities of psychiatric symptoms can also occur posing a further challenge for correct diagnosis. Proper recognition allows early diagnosis and adequate treatment, preventing hazardous antipsychotic use in these patients.

RESUMO A síndrome de Ekbom, também conhecida como delírio parasitário ou parasitose psicogênica, é uma condição rara na qual os pacientes apresentam crença fixa de estarem infestados por parasitas, vermes ou insetos, acompanhada de alucinações táteis (como prurido ou sensação dos parasitas andando sobre ou sob a pele). A síndrome pode ocorrer de forma idiopática ou associada a outras condições médicas ou uso de drogas. Este relato de caso descreve a ocorrência da síndrome de Ekbom em um paciente diagnosticado com Demência com corpos de Lewy (DCL), uma doença degenerativa que comumente se apresenta com desordens de sensopercepção e pensamento, e outros sintomas neuropsiquiátricos. A alucinação visual é considerada um dos critérios diagnósticos nucleares, entretanto outras modalidades de sintomas psiquiátricos podem ocorrer criando desafios adicionais ao diagnóstico correto. O reconhecimento apropriado permite o diagnóstico precoce e tratamento adequado, prevenindo o uso arriscado de antipsicóticos nesses pacientes.

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BACKGROUND: Early detection of neurodegenerative diseases is essential for treatment and proper care of these patients. Screening tools available today are effective for several types of dementia. However, there is no one specific for Lewy Body Dementia (LBD). OBJECTIVES: The aim of this paper is to present a tool for early detection of LBD, accessible even for non-medical staff. METHODS: We stratified subjects (MMSE>20) into four groups: health controls (HC), Mild Cognitive Impairment (MCI), LBD and other dementias (Alzheimer and vascular). All subjects (age range 50-90) were examined with a comprehensive neuropsychological and neuropsychiatric evaluation, as well as neuroimaging to differentiate diagnosis between groups, fulfilling corresponding criteria. Both neurologists and neuropsychologists were blind to the performance on clinical evaluations and ASI, respectively. The sensitivity and specificity of the instrument were determined to differentiate LBD from other groups. RESULTS: We evaluated 427 subjects, 91 HC, 140 with MCI and 196 with dementia. In the dementia group, 75 were diagnosed with LBD and 121 with other dementias. ASI total score was 12.7±0.4 for LBD, 2.9±0.2 for HC, 5±0.7 for MCI, and 5.4±2.6 for other causes of dementia. ROC curve analysis showed a sensitivity of 90.7% and a specificity of 93.6% stands, with 9 as the cutoff with better test performance compared against other groups. CONCLUSION: ASI is a brief screening tool for LBD with high sensitivity and specificity and useful even for non-medical staff.

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La demencia por cuerpos de Lewy y la enfermedad de Parkinson son dos síndromes comunes con signos y síntomas similares que hacen difícil establecer un diagnóstico exacto, especialmente en las etapas intermedias y tardías de cada cuadro clínico en particular. La enfermedad de Parkinson es una entidad lenta y progresiva que se caracteriza por temblor de reposo, rigidez, bradiscinesias e inestabilidad postural. En ella, los síntomas neurocognitivos y conductuales como la depresión, la disfunción ejecutiva y atencional, la baja fluidez verbal y las fallas de memoria inmediata pueden aparecer desde las etapas iniciales de la enfermedad e ir empeorando y progresando, cuando aparece un cuadro demencial secundario a la enfermedad. Por su parte, la enfermedad por cuerpos de Lewy se considera un cuadro neurodegenerativo que se ha asociado a la presencia de cuerpos de Lewy a nivel cortical y subcortical y se caracteriza por signos extrapiramidales, fluctuaciones cognitivas y alucinaciones visuales. En ella los síntomas neurocognitivos y conductuales son "fluctuantes" en lo relacionado con el nivel de consciencia, las funciones ejecutivas y atencionales, la memoria episódica y la presencia/ausencia de alucinaciones visuales. Las diferencias sutiles de ambas enfermedades exigen una revisión exhaustiva en la evolución de los síntomas. La evaluación neuropsicológica como herramienta diagnóstica se limita en tanto que no reemplaza, los estudios de imagen y otros hallazgos neuropatológicos para el diagnóstico definitivo, pero permite objetivar el perfil neuropsicológico más propio de cada enfermedad, en particular para un diagnóstico más preciso.

Lewy body dementia and Parkinson´s disease are two frequent syndromes that share similar signs and symptoms, especially during intermediate and chronic phases of each particular clinical picture, making an accurate diagnosis very difficult to establish. Parkinson’s disease is a slow and progressive disorder characterized by tremor at rest, stiffness, bradykinesia and postural imbalance. Many neurocognitive and behavioral symptoms such as depression, executive and attentional dysfunction, lower verbal fluency and immediate memory failures can appear in early stages of the disease, increasing and progressing as a secondary dementia develops. Lewy body dementia is considered a neurodegenerative disorder associated to Lewy bodies in both cortical and subcortical regions. It is characterized by the presence of extrapyramidal features, cognitive fluctuation and visual hallucinations. Neurocognitive and behavioral symptoms fluctuate concerning level of consciousness, executive and attentional function, episodic memory and the presence/absence of visual hallucinations. Subtle differences in both disorders demand an exhaustive review of symptom´s evolution. Neuropsychological evaluation as a diagnostic tool is limited. It cannot replace neuroimaging studies and other neuropathological findings for a definite diagnosis, but determines each neuropsychological profile in particular for a more accurate diagnosis.

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Dementia with Parkinson's disease represents a controversial issue in the complex group of alpha-synucleinopathies. The author acknowledges the concept of a "continuum" between Parkinson disease's (PD), Lewy body dementia (LBD), and dementia in Parkinson's disease (PDD). However, the practicing neurologist needs to identify the phenotypic signs of each dementia. The treatment and prognosis are different in spite of the overlaps between them. The main aim of this review was to characterize the clinical diagnoses of dementia associated with Parkinson's disease (PDD). Secondarily, the review discussed some epidemiological and neuropsychological issues. Selection of articles was not systematic and reflects the author's opinion, where the main text selected was the recommendations from the Movement Disorder Society Task Force for PDD diagnosis. The Pub Med, OVID, and Proquest data bases were used for the search.

Demência com doença de Parkinson constitui um assunto controverso no complexo grupo das alfa-sinucleinopatias. O autor admite o conceito de um "continuum" entre doença de Parkinson (DP), demência com corpos de Lewy (DCL) e demência na doença de Parkinson (DDP). Todavia, neurologistas necessitam identificar os sinais fenotípicos de cada uma. O tratamento e prognóstico são diferentes, apesar das sobreposições entre elas. O primeiro objetivo desta revisão foi o de caracterizar o diagnóstico clínico de demência associada à DP. Secundariamente, a revisão discute alguns aspectos epidemiológicos e neuropsicológicos. A seleção dos artigos não foi sistemática e reflete a opinião do autor, escolhendo como texto principal as recomendações da Força Tarefa da Sociedade de Transtornos do Movimento para diagnóstico de DDP. Foram utilizados as bases de dados do Pub Med, OVID e Proquest como bases de dados.

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A 79-year-old male with cognitive impairment and parkinsonism is described. The use of the clinical method is highlighted as a sure way of leading to the eventual disgnosis of Dementia with Lewy Bodies.

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