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INTRODUCTION: The study aims to use power spectrum changes in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), preclinical stages of Alzheimer's disease (AD), for future biomarker studies in early AD diagnosis. METHODS: We recruited 23 SCD and 32 aMCI subjects and conducted comparative analysis using relative power spectral density (PSD). Automated preprocessing and statistical analysis were performed using iSync Brain® (iMediSync Inc., Republic of Korea) (https://isyncbrain.com/). RESULTS: Theta band power in the temporal region was 14.826 ± 7.2394 for the SCD group and 20.003 ± 10.1768 for the aMCI group. In the parietal region, theta band power was 13.614 ± 7.5689 for SCD and 19.894 ± 11.1387 for aMCI. Beta1 band power in the frontal region was 6.639 ± 2.2904 for SCD and 5.465 ± 1.8907 for aMCI, and in the temporal region it was 7.359 ± 2.5619 for SCD and 5.921 ± 2.1605 for aMCI. CONCLUSION: PSD analysis of resting-state EEG predicted SCD, a preclinical stage of AD. This cross-sectional study observed electrical-physiological characteristics of preclinical AD; however, follow-up studies are needed to evaluate predictive value for future cognitive decline.
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Doença de Alzheimer , Disfunção Cognitiva , Eletroencefalografia , Humanos , Disfunção Cognitiva/psicologia , Masculino , Feminino , Idoso , Doença de Alzheimer/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Ritmo TetaRESUMO
INTRODUCTION: Alzheimer's disease (AD) involves the complement cascade, with complement component 3 (C3) playing a key role. However, the relationship between C3 and amyloid beta (Aß) in blood is limited. METHODS: Plasma C3 and Aß oligomerization tendency (AßOt) were measured in 35 AD patients and 62 healthy controls. Correlations with cerebrospinal fluid (CSF) biomarkers, cognitive impairment, and amyloid positron emission tomography (PET) were analyzed. Differences between biomarkers were compared in groups classified by concordances of biomarkers. RESULTS: Plasma C3 and AßOt were elevated in AD patients and in CSF or amyloid PET-positive groups. Weak positive correlation was found between C3 and AßOt, while both had strong negative correlations with CSF Aß42 and cognitive performance. Abnormalities were observed for AßOt and CSF Aß42 followed by C3 changes. DISCUSSION: Increased plasma C3 in AD are associated with amyloid pathology, possibly reflecting a defense response for Aß clearance. Further studies on Aß-binding proteins will enhance understanding of Aß mechanisms in blood.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Amiloide , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Complemento C3 , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons/métodos , Proteínas tau/líquido cefalorraquidianoRESUMO
For automatic EEG diagnosis, this paper presents a new EEG data set with well-organized clinical annotations called Chung-Ang University Hospital EEG (CAUEEG), which has event history, patient's age, and corresponding diagnosis labels. We also designed two reliable evaluation tasks for the low-cost, non-invasive diagnosis to detect brain disorders: i) CAUEEG-Dementia with normal, mci, and dementia diagnostic labels and ii) CAUEEG-Abnormal with normal and abnormal. Based on the CAUEEG dataset, this paper proposes a new fully end-to-end deep learning model, called the CAUEEG End-to-end Deep neural Network (CEEDNet). CEEDNet pursues to bring all the functional elements for the EEG analysis in a seamless learnable fashion while restraining non-essential human intervention. Extensive experiments showed that our CEEDNet significantly improves the accuracy compared with existing methods, such as machine learning methods and Ieracitano-CNN (Ieracitano et al., 2019), due to taking full advantage of end-to-end learning. The high ROC-AUC scores of 0.9 on CAUEEG-Dementia and 0.86 on CAUEEG-Abnormal recorded by our CEEDNet models demonstrate that our method can lead potential patients to early diagnosis through automatic screening.
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Disfunção Cognitiva , Aprendizado Profundo , Demência , Humanos , Eletroencefalografia/métodos , Algoritmos , Disfunção Cognitiva/diagnóstico , Demência/diagnósticoRESUMO
INTRODUCTION: Semantic dementia (SD) is a progressive neurodegenerative disease associated with impaired vocabulary that progresses to memory impairment. Post-mortem immunohistochemical analysis is the current reliable method of differentiating TDP-43 deposits in cortical tissue; no means of antemortem diagnosis exists in biofluids, let alone in plasma. METHODS: Here the multimer detection system (MDS) was used to quantify the oligomeric TDP-43 (o-TDP-43) concentrations in plasma of Korean SD patients (n = 16, 6 male, 10 female, ages 59-87). The o-TDP-43 concentrations were compared with the total TDP-43 (t-TDP-43) concentrations quantified through conventional enzyme-linked immunosorbent assay (ELISA). RESULTS AND DISCUSSION: Only MDS showed a significant increase in o-TDP-43 concentrations in the plasma of patients with SD compared to other neurodegenerative disorders and normal controls (p < 0.05). Based on these results, o-TDP-43 concentrations through the application of MDS may be a useful plasma biomarker in SD-FTD (frontotemporal dementia) diagnosis.
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Demência Frontotemporal , Doenças Neurodegenerativas , Humanos , Masculino , Feminino , Doenças Neurodegenerativas/complicações , Proteínas de Ligação a DNA , República da CoreiaRESUMO
BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.
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Aspirina/administração & dosagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Cilostazol/administração & dosagem , Imageamento por Ressonância Magnética , Substância Branca , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Cilostazol/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: The tendency of amyloid-ß to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAß and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. METHODS: The performance of EDTA-based MDS-OAß in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAß level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset. RESULTS: The random forest model best-predicted amyloid PET positivity based on MDS-OAß combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAß, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAß value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%. CONCLUSIONS: The Random Forest model using EDTA-based MDS-OAß combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Ácido Edético , Peptídeos beta-Amiloides , Doença de Alzheimer/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Biomarcadores , Aprendizado de Máquina , Algoritmos , Disfunção Cognitiva/diagnósticoRESUMO
BACKGROUND: Donepezil 23 mg is considered for Alzheimer's disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. METHODS: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. RESULTS: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (-) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p > 0.05). CONCLUSIONS: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs ("Clinicaltrials.gov" No. NCT02550665 registered on September 15, 2015).
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Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peso Corporal , Inibidores da Colinesterase/efeitos adversos , Donepezila/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Indanos/efeitos adversos , Piperidinas/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: The present study examined self-reports and informant reports of cognitive function and discrepancies between the two reporting methods in healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and very mild Alzheimer disease (AD) using three questionnaires. METHODS: The study included a total of 300 individuals (mean age: 74.4 ± 5.7 y), including 130 HC, 70 SCD, 51 MCI, and 49 very mild AD patients. Self-ratings and informant ratings of cognitive function were assessed using the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), AD8, and Subjective Memory Complaints Questionnaire (SMCQ). Awareness of cognitive functioning was measured on the basis of the discrepancy scores between self-reports and informant reports. RESULTS: Group comparisons on questionnaire scores adjusting for age, education, and depressive symptoms showed that self-reports were lowest in HC than other groups, with no differences between SCD and MCI groups. Informant reports were lower in SCD than in MCI, while discrepancy scores were higher in SCD than in MCI (P < .001 for KDSQ-C and SMCQ; P = .076 for AD8). There were no differences in self-reports, informant reports, and discrepancy scores between MCI and AD groups. CONCLUSIONS: These results support the usefulness of informant-reported cognitive functioning to classify MCI among elderly with subjective cognitive complaints. In addition, discrepancies between self-reports and informant reports demonstrate that overestimation and underestimation of cognitive function may serve as a clinical indicator of SCD and MCI across the cognitive continuum, respectively.
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Doença de Alzheimer/psicologia , Conscientização/fisiologia , Cognição/fisiologia , Disfunção Cognitiva/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Autoavaliação Diagnóstica , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Autorrelato , Inquéritos e QuestionáriosRESUMO
Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs.
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Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Demência/epidemiologia , Serviços de Saúde para Idosos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Atividades Cotidianas , Idoso , Betacoronavirus , Encéfalo/fisiopatologia , COVID-19 , Cuidadores , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , Infecções por Coronavirus/complicações , Cuidados Críticos , Demência/complicações , Humanos , Hipóxia , Sistema Imunitário , Inflamação , Casas de Saúde , Pneumonia Viral/complicações , Medicina Preventiva , Saúde Pública , Fatores de Risco , SARS-CoV-2 , Isolamento Social , TelemedicinaRESUMO
The cerebellum has recently been highlighted as a key neural substrate responsible for dystonia. A 57-year-old female presented with isolated focal leg dystonia that developed 8 years after acute cerebellar infarction. Brain magnetic resonance imaging showed an old cerebellar infarct in the right anterior cerebellum. Low-frequency cerebellar repetitive transcranial magnetic stimulation on the right cerebellum partially improved dystonia in this patient. This case provides valuable evidence on cerebellar mechanisms related to the development of dystonia in a topographically specific manner. Cerebellar brain stimulation can be a potential therapeutic strategy for patients with dystonia.
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Infarto Encefálico/terapia , Cerebelo/irrigação sanguínea , Distúrbios Distônicos/terapia , Perna (Membro) , Estimulação Magnética Transcraniana/métodos , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/etiologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Korea has a periodic general health check-up program that uses the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a cognitive dysfunction screening tool. The Alzheimer Disease 8 (AD8) and Subjective Memory Complaints Questionnaire (SMCQ) are also used in clinical practice. We compared the diagnostic ability of these screening questionnaires for cognitive impairment when completed by participants and their caregivers. Hence, we aimed to evaluate whether the SMCQ or AD8 is superior to the KDSQ-C and can be used as its replacement. METHODS: A total of 420 participants over 65 years and their informants were recruited from 11 hospitals for this study. The patients were grouped into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C, AD8, and SMCQ were completed separately by participants and their informants. RESULTS: A receiver operating characteristic analysis of questionnaire scores completed by participants showed that the areas under the curve (AUCs) for the KDSQ-C, AD8, and SMCQ for diagnosing dementia were 0.75, 0.8, and 0.73, respectively. Regarding informant-completed questionnaires, the AD8 (AUC of 0.93), KDSQ-C (AUC of 0.92), and SMCQ (AUC of 0.92) showed good discriminability for dementia, with no differences in discriminability between the questionnaires. CONCLUSION: When an informant-report is possible, we recommend that the KDSQ-C continues to be used in national medical check-ups as its discriminability for dementia is not different from that of the AD8 or SMCQ. Moreover, consistent data collection using the same questionnaire is important. When an informant is not available, either the KDSQ-C or AD8 may be used. However, in the cases of patient-reports, discriminability is lower than that for informant-completed questionnaires.
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Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cognição/fisiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Curva ROC , República da Coreia , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. METHODS: Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer's disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. RESULTS: The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The 'time orientation' and '3-word recall' score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. CONCLUSIONS: The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.
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Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Aprendizado de Máquina , Testes Neuropsicológicos , Fatores Etários , Algoritmos , Conjuntos de Dados como Assunto , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Sensibilidade e EspecificidadeRESUMO
The number of patients with Alzheimer's disease (AD) is rapidly increasing in Asia. Mutations in the amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes can cause autosomal dominant forms of early-onset AD (EOAD). Although these genes have been extensively studied, variant classification remains a challenge, highlighting the need to colligate mutations across populations. In this study, we performed a genetic screening for mutations in the APP, PSEN1, and PSEN2 genes in 200 clinically diagnosed EOAD patients across four Asian countries, including Thailand, Malaysia, the Philippines, and Korea, between 2009 and 2018. Thirty-two (16%) patients presented pathogenic APP, PSEN1, or PSEN2 variants; eight (25%), 19 (59%), and five (16%) of the 32 patients presented APP, PSEN1, and PSEN2 variants, respectively. Among the 21 novel and known non-synonymous variants, five APP variants were found in Korean patients and one APP variant was identified in a Thai patient with EOAD. Nine, two, and one PSEN1 mutation was found in a Korean patient, Malaysian siblings, and a Thai patient, respectively. Unlike PSEN1 mutations, PSEN2 mutations were rare in patients with EOAD; only three variants were found in Korean patients with EOAD. Comparison of AD-causative point mutations in Asian countries; our findings explained only a small fraction of patients, leaving approximately 84% (p = 0.01) of autosomal dominant pedigrees genetically unexplained. We suggest that the use of high-throughput sequencing technologies for EOAD patients can potentially improve our understanding of the molecular mechanisms of AD.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Povo Asiático/genética , Mutação , Presenilina-1/genética , Presenilina-2/genética , Adulto , Idade de Início , Idoso , Alelos , Substituição de Aminoácidos , Precursor de Proteína beta-Amiloide/química , Ásia/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Presenilina-1/química , Presenilina-2/química , Domínios ProteicosRESUMO
Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), COL4A1/2-related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.
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Doenças de Pequenos Vasos Cerebrais/genética , Leucoencefalopatias/genética , Acidente Vascular Cerebral/genética , Animais , Demência Vascular/metabolismo , Humanos , Esferoides Celulares/metabolismoRESUMO
BACKGROUND: Cerebral small vessel disease (SVD) has been suggested to be more common in Asians compared with Caucasians. However, data from population-based studies in Asia are lacking. We report on the prevalence, risk factors and consequences of SVD from contemporary studies in three Asian countries using 3-Tesla MRI for the evaluation of SVD. METHODS: Clinical, cognitive and 3-Tesla brain MRI assessments were performed among participants of three studies from Singapore, Hong Kong and Korea. SVD markers include white matter hyperintensities (WMHs) using the modified Fazekas scale, lacunes and microbleeds. Cognition was assessed using the Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Adjustments were made for age, sex and cardiovascular risk factors. RESULTS: A total of 1797 subjects were available for analysis (mean age: 70.1±6.3 years and 57% women). The prevalence of confluent WMH was 36.6%, lacunes, 24.6% and microbleeds, 26.9%. Presence of all three SVD markers showed a steeper increase with increasing age rising from 1.9% in the lowest to 46.2% in the highest 5-year age strata. The major risk factors for the increased severity of SVD markers were advancing age and hypertension. Moreover, increasing severity of SVD markers was independently associated with worse performance on MMSE and MoCA. CONCLUSION: Elderly Asians have a high burden of SVD which was associated with cognitive dysfunction. This suggests that SVD markers should be a potential target for treatment in clinical trials so as to delay progression of cerebrovascular disease and potentially cognitive decline.
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Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Transtornos Cognitivos/diagnóstico , Comparação Transcultural , Feminino , Hong Kong , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , SingapuraRESUMO
OBJECTIVE: To date, data regarding the efficacy of acetylcholinesterase inhibitors in preventing postoperative delirium (POD) are inconsistent and conflicting. Older individuals with cognitive dysfunction are thought to show POD more frequently. Our aim was to study the effectiveness of rivastigmine prophylaxis on the incidence, severity, and risk factors for POD in older patients with cognitive impairment undergoing hip fracture surgery. METHODS: Of 62 older patients with cognitive impairment about to undergo surgery after a hip fracture, 31 were randomly assigned to receive a rivastigmine patch from 3 days before to 7 days after the operation (Group I), and the other 31 did not receive a rivastigmine patch (Group II). The two groups were compared with regard to incidence and severity of delirium on postoperative days 2 or 3 and 7. Multivariate logistic regression analysis was performed to assess factors associated with POD. RESULTS: Postoperative delirium occurred in five Group I patients and 14 Group II patients (p = 0.013). The mean severity of delirium in the two groups as determined by the Delirium Rating Scale was 2.2 and 6.2 respectively (p = 0.033). The odds ratio for POD was 0.259 (95% CI: 0.074-0.905, p = 0.034) after adjusting for American Society of Anesthesiologists score (p = 0.058), age (p = 0.203), and gender (p = 0.560). There were no rivastigmine-related perioperative complications. CONCLUSION: Perioperative rivastigmine patch application could reduce the occurrence of POD in older patients with low cognitive status. Copyright © 2016 John Wiley & Sons, Ltd.
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Inibidores da Colinesterase/administração & dosagem , Disfunção Cognitiva/complicações , Delírio/prevenção & controle , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Rivastigmina/administração & dosagem , Rivastigmina/uso terapêutico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Feminino , Humanos , Incidência , Masculino , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
Viral meningitis is the most common cause of aseptic meningitis. Use of the polymerase chain reaction (PCR) has increased the ability to determine the etiology of viral meningitis. This study used PCR analysis to evaluate the etiology of aseptic meningitis in 177 previously healthy adults over a 5-year period, as well as analyzing the clinical characteristics, cerebrospinal fluid (CSF) findings, and prognosis according to each etiology. The most frequent cause of aseptic meningitis was enterovirus (EV), followed by varicella zoster virus (VZV). Patients with EV meningitis were significantly younger than those with VZV meningitis. The percentage of lymphocytes in white blood cell counts and protein concentrations in the CSF differed significantly among patients with EV, VZV and meningitis of undetermined etiology. Younger age and lower percentage of lymphocyte and protein level in CSF analysis may be suggestive of EV meningitis. Further prospective studies are warranted to identify the correlations between the clinical characteristics and the etiologies of meningitis.
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Líquido Cefalorraquidiano/química , Meningite Asséptica/patologia , Meningite Asséptica/virologia , Vírus/classificação , Vírus/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Contagem de Linfócitos , Masculino , Meningite Asséptica/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Proteínas/análise , Estudos Retrospectivos , Vírus/genética , Adulto JovemRESUMO
BACKGROUND: Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. CASE REPORT: A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. CONCLUSION: We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.
Assuntos
Doença de Alzheimer/genética , Modelos Genéticos , Presenilina-1/química , Presenilina-1/genética , Idade de Início , Doença de Alzheimer/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND: Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. METHODS: We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. RESULTS: In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in <30% of patients. With progression toward stage 3, DWI hyperintensities in the subcortical nucleus increased, with a sustained higher rate of hyperintensities in the limbic and neocortical regions. With gradual progression to stage 4, the sensitivity of CSF 14-3-3 protein testing and EEG decreased and increased, respectively within limited data. CONCLUSIONS: Understanding disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis.
Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Proteínas 14-3-3/líquido cefalorraquidiano , Idoso , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Imagem de Difusão por Ressonância Magnética/métodos , Progressão da Doença , Eletroencefalografia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Low 25-hydroxyvitamin D (25(OH)D) concentrations have been shown to predict risk of cardiovascular disease and all-cause mortality. Although the prevalence of 25(OH)D deficiency is high in patients with acute stroke, the prognostic value of 25(OH)D in stroke has not been clearly established. The purpose of this study was to determine whether the baseline serum 25(OH)D level was associated with the functional outcome in patients with acute ischemic stroke. METHODS: From June 2011 to January 2014, consecutive patients with acute ischemic stroke within 7 days of symptom onset were enrolled in this study from a prospectively maintained stroke registry. Serum 25(OH)D level was measured at admission. Clinical and laboratory data including stroke severity using the National Institute of Health Stroke Scale (NIHSS) score were collected during admission, and the functional outcome at 3 months was assessed by modified Rankin scale (mRS). The association between the baseline 25(OH)D level and a good functional outcome (mRS 0-2) at 3 months was analyzed by multiple logistic regression models. RESULTS: A total of 818 patients were enrolled in this study. Mean age was 66.2 (±12.9) years, and 40.5% were female. The mean 25(OH)D level was 47.2 ± 31.7 nmol/l, and the majority of patients met vitamin D deficient status (<50 nmol/l; 68.8%), while an optimal vitamin D level (≥75 nmol/l) was present in only 13.6% of the patients, and 436 (53.3%) patients showed good functional outcome at 3 months. Serum 25(OH)D levels in patients with good outcomes were significantly higher than those with poor outcome (50.2 ± 32.7 vs. 43.9 ± 30.0 nmol/l, p = 0.007). The 3-month functional outcome was significantly associated with month-specific 25(OH)D quartiles in multivariable logistic regression analysis. After adjustment for age and sex, the highest 25(OH)D quartile group had higher tendency for good functional outcome at 3 months (odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.13-2.51). After fully adjusting for other potential confounders, such as stroke severity and vascular risk factors, the association was further strengthened with an OR (95% CI) of 1.90 (1.14-3.16). Other factors associated with good functional outcome in multivariable analysis were younger age, lower initial NIHSS score and absence of diabetes. CONCLUSIONS: This study suggests that serum 25(OH)D level is an independent predictor of functional outcome in patients with acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.