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Increasing evidence suggests that alterations in cerebral microvasculature play a critical role in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture of AD transgenic (Tg) mice and compare it with that of non-Tg mice using brain microvascular indices obtained by MRI. Seven non-Tg mice and 10 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after the injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculating ΔR2* and ΔR2, the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density, mean vessel-weighted image (MvWI) and blood volume fraction (BVf) were mapped. Voxel-based analyses and region of interest (ROI)-based analyses were performed to compare the indices of the non-Tg and Tg groups. Voxel comparisons showed that BVf, mVD, VSI and MvWI were greater in the Tg group than in the non-Tg group. Additionally, the ROI-based analysis showed that ΔR2*, BVf, mVD, MvWI and VSI increased in several brain regions of the Tg group compared with those in the non-Tg group. VSI and mVD increased in Tg mice; these findings indicated microvascular disruption in the brain that could be related to damage to the neurovascular unit in AD caused by cerebral amyloid angiopathy.
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Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Microvasos/diagnóstico por imagem , Doença de Alzheimer , Animais , Encéfalo/citologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Camundongos TransgênicosRESUMO
Parosmia, defined as the distorted perception of an odor stimulus, has been reported to be associated with head trauma, upper respiratory tract infections, sinonasal diseases, and toxin/drug consumption. To date, little is known about parosmia in right-lateralized semantic variant primary progressive aphasia. A 60-year-old right-handed man presented with a 2-year history of parosmia and prosopagnosia. Brain magnetic resonance imaging demonstrated severe atrophy of the right anterior and mesial temporal lobe, particularly in the fusiform cortex and the regions known as the primary olfactory cortex. 18F-fluorodeoxyglucose position emission tomography showed asymmetric hypometabolism of the bilateral temporal lobes (right > left). We clinically diagnosed him with right-lateralized semantic variant primary progressive aphasia. As the right hemisphere is known to be more involved in the processing of pleasant odors than the left hemisphere, we speculate that the unique manifestation of parosmia observed in this patient might be associated with the lateralization of the olfactory system.
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Afasia Primária Progressiva/diagnóstico por imagem , Lateralidade Funcional , Transtornos do Olfato , Afasia Primária Progressiva/patologia , Atrofia/patologia , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Transtornos do Olfato/etiologia , Tomografia por Emissão de Pósitrons , Prosopagnosia/etiologia , Lobo Temporal/patologiaRESUMO
Alzheimer's disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-ß (Aß) plaques and neurofibrillary tangles in the brain. During the progression of AD, microglia can be polarized from anti-inflammatory M2 to pro-inflammatory M1 phenotype. The activation of triggering receptor expressed on myeloid cells 2 (TREM2) may result in microglia phenotype switching from M1 to M2, which finally attenuated Aß deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate Aß pathology and cognitive deficits in AD; however, the therapeutic mechanisms of LDIR against AD-related pathology have been little studied. First, we reconfirm that LDIR (two Gy per fraction for five times)-treated six-month 5XFAD mice exhibited (1) the reduction of Aß deposition, as reflected by thioflavins S staining, and (2) the improvement of cognitive deficits, as revealed by Morris water maze test, compared to sham-exposed 5XFAD mice. To elucidate the mechanisms of LDIR-induced inhibition of Aß accumulation and memory loss in AD, we examined whether LDIR regulates the microglial phenotype through the examination of levels of M1 and M2 cytokines in 5XFAD mice. In addition, we investigated the direct effects of LDIR on lipopolysaccharide (LPS)-induced production and secretion of M1/M2 cytokines in the BV-2 microglial cells. In the LPS- and LDIR-treated BV-2 cells, the M2 phenotypic marker CD206 was significantly increased, compared with LPS- and sham-treated BV-2 cells. Finally, the effect of LDIR on M2 polarization was confirmed by detection of increased expression of TREM2 in LPS-induced BV2 cells. These results suggest that LDIR directly induced phenotype switching from M1 to M2 in the brain with AD. Taken together, our results indicated that LDIR modulates LPS- and Aß-induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as Aß deposition and memory loss.
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Doença de Alzheimer/metabolismo , Microglia/metabolismo , Microglia/efeitos da radiação , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , Fenótipo , Radiação Ionizante , Receptores Imunológicos/metabolismoRESUMO
Ophthalmopathy related to thyroid disease is due mainly to diffuse periorbital or eye muscle inflammation. It is more common in Grave's hyperthyroidism and rare in Hashimoto's hypothyroidism. Here we report a case of recurrent oculomotor nerve palsy associated with autoimmune hypothyroidism. Brain MRI revealed enhancement of the oculomotor nerves. Despite thyroid hormone replacement therapy, oculomotor nerve palsy recurred at the side contralateral to the initially involved nerve and the autoimmune antibody titer remained high. The symptom was responsive to high-dose steroid therapy.
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Doença de Hashimoto/complicações , Doenças do Nervo Oculomotor/etiologia , Tireoidite Autoimune/complicações , Adolescente , Feminino , Doença de Hashimoto/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Humanos , Imageamento por Ressonância Magnética , Doenças do Nervo Oculomotor/tratamento farmacológico , Doenças do Nervo Oculomotor/patologia , Recidiva , Esteroides/uso terapêutico , Tireoidite Autoimune/tratamento farmacológicoRESUMO
The objectives of this study were to investigate how the extra-neurite conductivity (EC) and intra-neurite conductivity (IC) were reflected in Alzheimer's disease (AD) patients compared with old cognitively normal (CN) people and patients with amnestic mild cognitive impairment (MCI) and to evaluate the association between those conductivity values and cognitive decline. To do this, high-frequency conductivity (HFC) at the Larmor frequency was obtained using MRI-based electrical property tomography (MREPT) and was decomposed into EC and IC using information of multi-shell multi-gradient direction diffusion tensor images. This prospective single-center study included 20 patients with mild or moderate AD, 25 patients with amnestic MCI, and 21 old CN participants. After decomposing EC and IC from HFC for all participants, we performed voxel-based and regions-of-interest analyses to compare conductivity between the three participant groups and to evaluate the association with either age or the Mini-Mental State Examination (MMSE) scores. We found increased EC in AD compared to CN and MCI. EC was significantly negatively associated with MMSE scores in the insula, and middle temporal gyrus. EC might be used as an imaging biomarker for helping to monitor cognitive function.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Projetos Piloto , Estudos Prospectivos , Neuritos , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Apolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis. OBJECTIVE: To predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods. METHODS: We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE ε4 carriers and 52 noncarriers) and scanned them with three-dimensional (3D) T1-weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini-mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE ε4 carrier with different ML models. RESULTS: The best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone. CONCLUSION: Our results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE ε4 status and identifying individuals at risk of AD progression.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Apolipoproteína E4/genética , Alelos , Apolipoproteínas E/genética , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Genótipo , Cognição , Imageamento por Ressonância Magnética/métodos , Atrofia/patologiaRESUMO
Background: Blood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people. Methods: This study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1ß), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aß42 (mAß), oligomeric Aß42 (oAß), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses. Results: GMV and gwBTV significantly decreased as the levels of IL1ß and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1ß, P-tau, and T-tau in the hippocampus. Specifically, IL1ß and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3. Conclusion: The observed association between brain tissue volume loss and elevated levels of IL1ß and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1ß and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.
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Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
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INTRODUCTION: The objective of this study was to evaluate the effect of apolipoprotein E (APOE) epsilon 4 allele on regional cerebral perfusion (rCBF) changes using arterial spin labeling (ASL) magnetic resonance imaging (MRI) in subjects who are carriers or noncarriers of this risk factor for Alzheimer disease (AD). METHODS: Twenty-five subjects with AD, 25 with amnestic mild cognitive impairment (MCI) and 25 cognitively normal (CN) subjects underwent isotropic volumetric T1-weighted imaging and pulsed ASL MRI. All subjects were divided into carrier or noncarriers of the epsilon4 allele. Voxel-based statistical analyses were performed among groups on rCBF by ANOVA tests. In each subject group, we also evaluated the rCBF change between carrier and noncarrier groups. RESULTS: rCBF was significantly reduced in AD subjects compared to other subjects. In CN and AD subjects, rCBF in the carrier group was significantly reduced in several areas of the brain compared with that of the noncarrier group. In the carrier group, rCBF was significantly increased in the right parahippocampal gyrus, the bilateral cingulate gyri and the right posterior cingulate on the MCI group in addition to the right superior frontal gyrus in the AD group. CONCLUSION: rCBF in the CN and AD groups were significantly reduced in the subjects with the carriers of the epsilon4 allele, which is a risk factor for Alzheimer's disease. In addition, rCBF in the MCI group was significantly increased in subjects who were carriers. Therefore, rCBF can be used as a biomarker to show disease progression in areas of the brain of MCI subjects.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Apolipoproteína E4/genética , Circulação Cerebrovascular , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Idoso , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/epidemiologia , Comorbidade , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Angiografia por Ressonância Magnética/estatística & dados numéricos , Masculino , Prevalência , Fluxo Sanguíneo Regional , República da Coreia/epidemiologia , Fatores de RiscoAssuntos
Peptídeos beta-Amiloides/metabolismo , Afasia Primária Progressiva/complicações , Transtornos Cognitivos/etiologia , Semântica , Idoso , Compostos de Anilina/metabolismo , Compostos de Anilina/farmacocinética , Afasia Primária Progressiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Ligação Proteica/efeitos dos fármacos , Estilbenos/metabolismo , Estilbenos/farmacocinética , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
BACKGROUND: Cognitive deficit is a common problem in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to prospectively evaluate if MRI can demonstrate microstructural volume loss and the diffusion anisotropic change in subjects with COPD, compared with cognitively normal (CN) subjects. METHODS: Six subjects with severe COPD, 13 with moderate COPD, and 12 CN subjects underwent isotropic volumetric T1-weighted imaging and diffusion tensor imaging (DTI). Voxel-based statistical analyses among groups were performed on brain volumes, fractional anisotropy (FA) and trace. Cognitive function tests were performed in all subjects, and the Cognitive function tests (CFT) scores were compared among the three groups. RESULTS: No significant regional difference in volume was found in both the severe and moderate COPD groups relative to the CN group. Comparing between severe COPD and CN, FA was reduced in both the cerebral cortices, and in frontoparietal periventricular white matter. The trace value of the severe COPD group was significantly higher in the cerebral cortices, and in frontoparietal periventricular white matter, than that of the CN group. The severe COPD group showed significantly lower scores in the language-related, visuospatial, and frontal executive functions compared to those of the CN and moderate COPD group. CONCLUSION: This study demonstrated that COPD could affect the axonal integrity in multiple brain regions, and change in DTI might be related with the severity of the COPD.
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Córtex Cerebral/patologia , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Imagem de Tensor de Difusão , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Anisotropia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Background: Conventional magnetic resonance imaging (MRI) techniques cannot demonstrate microvascular alterations in mild Alzheimer's disease (AD). Thus, the diagnosis of microvascular pathology commonly relies on postmortem. The purpose of this study was to evaluate alterations of microvascular structures in patients with AD using a 3T clinical MRI system with a commercially available contrast agent. Methods: Eleven patients with AD and 11 cognitively normal (CN) controls were included in this cross-sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a Gadolinium (Gd)-based contrast agent injection were calculated from images obtained with a multi-echo turbo spin-echo sequence and multi-echo gradient-echo sequence to obtain microvascular index maps of blood volume fraction (BVf), mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), and microvessel-weighted imaging (MvWI). Two-sample t-test was used to compare those values between the two groups. Correlation analysis was performed to evaluate the relationship between those values and age. Results: BVfs at the corpus callosum and at the thalamus were significantly increased in the AD group (P=0.024 and P=0.005, respectively). BVf at the gray matter (P=0.020) and white matter area (P=0.012) were also significantly increased in the AD group compared with the CN group. MvWIs at the hippocampus and parahippocampal gyrus were significantly increased in the AD group compared with the CN group (P=0.020 and P=0.006, respectively). Voxel-based analysis showed both mVD and VSI were significantly decreased at the prefrontal lobe in the AD group. Q were not significant difference between CN and AD groups. MvWI were significantly positively correlated with age. Conclusions: Microvascular index was a useful non-invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as increasing BVf and microvessel-weighted.
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Introduction: Alzheimer's disease (AD) presents typically gray matter atrophy and white matter abnormalities in neuroimaging, suggesting that the gray-white matter boundary could be altered in individuals with AD. The purpose of this study was to explore differences of gray-white matter boundary Z-score (gwBZ) and its tissue volume (gwBTV) between patients with AD, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) elderly participants. Methods: Three-dimensional T1-weight images of a total of 227 participants were prospectively obtained from our institute from 2006 to 2022 to map gwBZ and gwBTV on images. Statistical analyses of gwBZ and gwBTV were performed to compare the three groups (AD, MCI, CN), to assess their correlations with age and Korean version of the Mini-Mental State Examination (K-MMSE), and to evaluate their effects on AD classification in the hippocampus. Results: This study included 62 CN participants (71.8 ± 4.8 years, 20 males, 42 females), 72 MCI participants (72.6 ± 5.1 years, 23 males, 49 females), and 93 AD participants (73.6 ± 7.7 years, 22 males, 71 females). The AD group had lower gwBZ and gwBTV than CN and MCI groups. K-MMSE showed positive correlations with gwBZ and gwBTV whereas age showed negative correlations with gwBZ and gwBTV. The combination of gwBZ or gwBTV with K-MMSE had a high accuracy in classifying AD from CN in the hippocampus with an area under curve (AUC) value of 0.972 for both. Conclusion: gwBZ and gwBTV were reduced in AD. They were correlated with cognitive function and age. Moreover, gwBZ or gwBTV combined with K-MMSE had a high accuracy in differentiating AD from CN in the hippocampus. These findings suggest that evaluating gwBZ and gwBTV in AD brain could be a useful tool for monitoring AD progression and diagnosis.
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BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-ß (Aß) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. OBJECTIVE: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. METHODS: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aß42/Aß40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. CONCLUSIONS: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Estudos Prospectivos , Resultado do Tratamento , Peptídeos beta-Amiloides/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como AssuntoAssuntos
Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico , Neurossífilis/complicações , Neurossífilis/diagnóstico , Doenças Talâmicas/complicações , Doenças Talâmicas/diagnóstico , Idoso , Encéfalo/diagnóstico por imagem , Infarto Cerebral/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Neurossífilis/tratamento farmacológico , Doenças Talâmicas/tratamento farmacológicoRESUMO
This paper presents an automatic algorithm for the detection of respiratory events in patients using electrocardiogram (ECG) and respiratory signals. The proposed method was developed using data of polysomnogram (PSG) and those recorded from a patch-type device. In total, data of 1,285 subjects were used for algorithm development and evaluation. The proposed method involved respiratory event detection and apnea-hypopnea index (AHI) estimation. Handcrafted features from the ECG and respiratory signals were applied to machine learning algorithms including linear discriminant analysis, quadratic discriminant analysis, random forest, multi-layer perceptron, and the support vector machine (SVM). High performance was demonstrated when using SVM, where the overall accuracy achieved was 83% and the Cohen's kappa was 0.53 for the minute-by-minute respiratory event detection. The correlation coefficient between the reference AHI obtained using the PSG and estimated AHI as per the proposed method was 0.87. Furthermore, patient classification based on an AHI cutoff of 15 showed an accuracy of 87% and a Cohen's kappa of 0.72. The proposed method increases performance result, as it records the ECG and respiratory signals simultaneously. Overall, it can be used to lower the development cost of commercial software owing to the use of open datasets.
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Síndromes da Apneia do Sono , Dispositivos Eletrônicos Vestíveis , Algoritmos , Eletrocardiografia , Humanos , Polissonografia/métodos , Sono , Síndromes da Apneia do Sono/diagnósticoRESUMO
This paper proposes a robust method to screen patients with sleep apnea syndrome (SAS) using a single-lead electrocardiogram (ECG). This method consists of minute-by-minute abnormal breathing detection and apnea-hypopnea index (AHI) estimation. Heartbeat interval and ECG-derived respiration (EDR) are calculated using the single-lead ECG and used to train the models, including ResNet18, ResNet34, and ResNet50. The proposed method, using data from 1232 subjects, was developed with two open datasets and experimental data and evaluated using two additional open datasets and data acquired from an abdomen-attached wearable device (in total, data from 189 subjects). ResNet18 showed the best results, having an average Cohen's kappa coefficient of 0.57, in the abnormal breathing detection. Moreover, SAS patient classification, with 15 as the AHI threshold, yielded an average Cohen's kappa coefficient of 0.71. The results of patient classification were biased toward data from the wearable patch-type device, which may be influenced by different ECG waveforms. The proposed method is tuned with a sample of the data from the device, and the performance result of Cohen's kappa increased from 0.54 to 0.91 for SAS patient classification. Our method, proposed in this paper, achieved equivalent performance results with data recorded using an abdomen-attached wearable device and two open datasets used in previous studies, although the method had not used those data during model training. The proposed method could reduce the development costs of commercial software, as it was developed using open datasets, has robust performance throughout all datasets.
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Síndromes da Apneia do Sono , Dispositivos Eletrônicos Vestíveis , Humanos , Síndromes da Apneia do Sono/diagnóstico , Eletrocardiografia/métodos , Frequência Cardíaca , RespiraçãoRESUMO
Background: The previous studies reported increased concentrations of metallic ions, imbalanced Na+ and K+ ions, and the increased mobility of protons by microstructural disruptions in Alzheimer's disease (AD). Purpose: (1) to apply a high-frequency conductivity (HFC) mapping technique using a clinical 3T MRI system, (2) compare HFC values in the brains of participants with AD, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) elderly people, (3) evaluate the relationship between HFC values and cognitive decline, and (4) explore usefulness of HFC values as an imaging biomarker to evaluate the differentiation of AD from CN. Materials and Methods: This prospective study included 74 participants (23 AD patients, 27 amnestic MCI patients, and 24 CN elderly people) to explore the clinical application of HFC mapping in the brain from March 2019 to August 2021. We performed statistical analyses to compare HFC maps between the three participant groups, evaluate the association of HFC maps with Mini-Mental State Examination (MMSE) scores, and to evaluate the differentiation between the participant groups for HFC values for some brain areas. Results: We obtained a good HFC map non-invasively. The HFC value was higher in the AD group than in the CN and MCI groups. MMSE scores were negatively associated with HFC values. Age was positively associated with HFC values. The HFC value in the insula has a high area under the receiver operating characteristic (ROC) curve (AUC) value to differentiate AD patients from the CN participants (Sensitivity [SE] = 82, Specificity [SP] =97, AUC = 0.902, p < 0.0001), better than gray matter volume (GMV) in hippocampus (SE = 79, SP = 83, AUC = 0.880, p < 0.0001). The classification for differentiating AD from CN was highest by adding the hippocampal GMV to the insular HFC value (SE = 87, SP = 87, AUC = 0.928, p < 0.0001). Conclusion: High-frequency conductivity values were significantly increased in the AD group compared to the CN group and increased with age and disease severity. HFC values of the insula along with the GMV of the hippocampus can be used as an imaging biomarker to improve the differentiation of AD from CN.
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Progressive aggregation and protein misfolding are the initial fundamental indicators of neurodegenerative disorders such as Alzheimer's disease (AD). In this study, a highly sensitive and novel method to detect amyloid beta (Aß) biomarkers, which are a hallmark of AD, using an immunoassay platform-based interdigitated capacitive biosensor, has been explored. For several decades, aptamers have classified as a novel class of molecular recognition probes comprising single-stranded complementary DNA sequences that bind to their identified targets with high specificity and affinity by an in vitro technique called SELEX (systematic evolution of exponential and enrichment). Aptamers, often referred to as "chemical antibodies", possess several highly obvious features for clinical use. The proposed sensing bio-device was fabricated and glazed with oligomeric Aß (oAß) aptamer and anti-oAß antibody, functionalized onto a Pt/Ti-featured SiO2 substrate. Subsequently, analytical studies were conducted to confirm that the specificity, sensitivity, and selective detection of the oAß-based bioengineered surfaces facilitate a label-free approach. The bionic capacitive sensor achieved real-time detection within 5 s (faster response than ELISA) under the femto-molar range concentrations of oAß peptide in plasma using anti-oAß antibody and oAß aptamer with ultra-high affinity. Furthermore, the prepared capacitive biochip was selective against plasma-borne antigens and standby for 100 days at 4 °C. The developed biosensor is suitable for point-of-care (POC) diagnostic applications owing to its portability and scalability. Furthermore, the superior efficacy of oAß in identifying AD has huge potential for biomedical applications.
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Doença de Alzheimer , Técnicas Biossensoriais , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/análise , DNA de Cadeia Simples , Eletrodos , Humanos , Fragmentos de Peptídeos , Dióxido de SilícioRESUMO
The purpose of this study was to investigate myelin loss in both AD and mild cognitive impairment (MCI) patients with a new myelin water mapping technique within reasonable scan time and evaluate the clinical relevance of the apparent myelin water fraction (MWF) values by assessing the relationship between decreases in myelin water and the degree of memory decline or aging. Twenty-nine individuals were assigned to the cognitively normal (CN) elderly group, 32 participants were assigned to the MCI group, and 31 patients were assigned to the AD group. A 3D visualization of the short transverse relaxation time component (ViSTa)-gradient and spin-echo (GraSE) sequence was developed to map apparent MWF. Then, the MWF values were compared between the three participant groups and was evaluated the relationship with the degree of memory loss. The AD group showed a reduced apparent MWF compared to the CN and MCI groups. The largest AUC (area under the curve) value was in the corpus callosum and used to classify the CN and AD groups using the apparent MWF. The ViSTa-GraSE sequence can be a useful tool to map the MWF in a reasonable scan time. Combining the MWF in the corpus callosum with the detection of atrophy in the hippocampus can be valuable for group classification.