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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.

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.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-sampleBVfs 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.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.

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 (Aβ) 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 Aβ (oAβ) aptamer and anti-oAβ antibody, functionalized onto a Pt/Ti-featured SiO

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.

Background: Because Alzheimer’s Disease (AD) has very complicated pattern changes, it is difficult to evaluate it with a specific factor. Recently, novel machine learning methods have been applied to solve limitations. Objective: The objective of this study was to investigate the approach of classification and prediction methods using the Machine Learning (ML)-based Optimized Combination-Feature (OCF) set on Gray Matter Volume (GMV) and Quantitative Susceptibility Mapping (QSM) in the subjects of Cognitive Normal (CN) elderly, Amnestic Mild Cognitive Impairment (aMCI), and mild and moderate AD. Materials and Methods: 57 subjects were included: 19 CN, 19 aMCI, and 19 AD with GMV and QSM. Regions-of-Interest (ROIs) were defined at the well-known regions for rich iron contents and amyloid accumulation areas in the AD brain. To differentiate the three subject groups, the Support Vector Machine (SVM) with the three different kernels and with the OCF set was conducted with GMV and QSM values. To predict the aMCI stage, regression-based ML models were performed with the OCF set. The result of prediction was compared with the accuracy of clinical data. Results: In the group classification between CN and aMCI, the highest accuracy was shown using the combination of GMVs (hippocampus and entorhinal cortex) and QSMs (hippocampus and pulvinar) data using the 2nd SVM classifier (AUC = 0.94). In the group classification between aMCI and AD, the highest accuracy was shown using the combination of GMVs (amygdala, entorhinal cortex, and posterior cingulate cortex) and QSMs (hippocampus and pulvinar) data using the 2nd SVM classifier (AUC = 0.93). In the group classification between CN and AD, the highest accuracy was shown using the combination of GMVs (amygdala, entorhinal cortex, and posterior cingulate cortex) and QSMs (hippocampus and pulvinar) data using the 2nd SVM classifier (AUC = 0.99). To predict aMCI from CN, the exponential Gaussian process regression model with the OCF set using GMV and QSM data was shown the most similar result (RMSE = 0.371) to clinical data (RMSE = 0.319). Conclusion: The proposed OCF based ML approach with GMV and QSM was shown the effective performance of the subject group classification and prediction for aMCI stage. Therefore, it can be used as personalized analysis or diagnostic aid program for diagnosis.

Anti-dementia medications are widely prescribed to patients with Alzheimer’s dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format—the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009–2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-d-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

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.

Our research team recently published two relevant papers. In one study, we have seen the acute effect of low-dose ionizing irradiation (LDIR) did not reduce the amyloid-β (Aβ) protein concentration in brain tissue, yet significantly improved synaptic degeneration and neuronal loss in the hippocampus and cerebral cortex. Surprisingly, in another study, we could see late effect that the LDIR-treated mice showed significantly improved learning and memory skills compared with those in the sham group. In addition, Aβ concentrations were significantly decreased in brain tissue. Furthermore, the pro-inflammatory cytokine tumor necrosis factor-α was decreased and the anti-inflammatory cytokine transforming growth factor-β was increased in the brain tissue of 5xFAD mice treated with LDIR. Definitive clinical results for the safety and efficacy of LDIR have not yet been published and, despite the promising outcomes reported during preclinical studies, LDIR can only be applied to patients with Alzheimer’s disease dementia when clinical results are made available. In addition, in the case of LDIR, additional large-scale clinical studies are necessary to determine the severity of Alzheimer’s disease dementia, indications for LDIR, the total dose to be irradiated, fraction size, and intervals of LDIR treatment. The purpose of this review is to summarize the mechanism of LDIR based on existing preclinical results in a way that is useful for conducting subsequent clinical research.

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.

Rationales: Cholinergic modification by anticholinergic medication can produce adverse effects in central nervous system (CNS) and cyclopentolate is an antimuscarinic agent widely used for ophthalmologic management. We demonstrate a rare case of hyperactive delirium caused by topical administration of cyclopentolate in a patient with amnestic mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Patient concerns: A 74-year-old man showed acute confusion after preparation for cataract operation in day surgery clinic. The patient became confused and agitated after instillation of topical cyclopentolate drop into the eye and the symptoms persisted over several hours. Diagnosis: Previously the patient had been diagnosed with amnestic MCI with the finding of bilateral medial temporal atrophy on brain magnetic resonance imaging. 18F-flutemetamol positron emission tomography scan demonstrated multifocal amyloid deposition in the brain. Interventions: The patient was closely observed with the supportive management. Outcomes: The patient began to recover 5 h after the onset of symptoms and the cognitive function was reverted to previous state within 24 h. Lessons: It is well known that several drugs with anticholinergic effects used in perioperative periods make the patients susceptible to delirium, but even the topical administration of cyclopentolate for cataract surgery also produce adverse CNS effects in a vulnerable patient who is diagnosed with MCI due to AD in this case.

Background: The aim of the present study was to investigate the associations between thyroid hormones, cognitive performance, and apolipoprotein E (APOE) genotype in euthyroid patients with subjective cognitive decline (SCD). Methods: We recruited 197 euthyroid patients that fulfilled the criteria for SCD. All participants were classified into APOE ε4 carriers and non-carriers based on the presence of the APOE ε4 allele. Patients with SCD who had the APOE ε2/ε4 genotype were excluded from the study. We then performed correlation and regression analyses to evaluate the associations between cognitive performance and thyroid hormones in APOE ε4 carriers and non-carriers. Results: We found no significant differences in cognitive function between APOE ε4 carriers and non-carriers. However, higher levels of triiodothyronine (T3) were associated with better verbal memory performance (immediate and delayed recall tasks) in APOE ε4 carriers, whereas a negative association was found in APOE ε4 non-carriers. Furthermore, there was a significant interactive effect of APOE ε4 status and T3 levels on verbal memory performance (immediate and delayed recall tasks). Conclusions: These findings suggest that in patients with SCD, T3 might have a protective effect on memory in those who are APOE ε4 carriers. The differential susceptibility hypothesis would thus support a gene-by-hormone crossover interaction between APOE ε4 allele and T3 in this study. Early identification and intervention of high-risk individuals for cognitive decline is important to establish new strategies for preventing dementia.

Purpose Growing evidence suggests that alterations of the 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 in the AD transgenic (Tg) mice model compared with non-Tg mice using brain microvascular indices obtained by MRI.Methods Seven non-Tg mice and ten 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 injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculation of the relaxation rate difference of ΔR2* and ΔR2, the microvascular indices of the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density (Q), mean vessel-weighted image (MvWI), and blood volume fraction (BVf) were mapped. The voxel-based analyses and regions-of-interest (ROIs)-based analyses were performed to compare the indices between the non-Tg and Tg groups.Results The BVf, mVD, VSI, and MvWI were greater in the Tg group than in the non-Tg group based on voxel comparisons. Additionally, the ROIs-based analysis showed that ΔR2*, BVf, mVD, MvWI, and VSI were increased in the Tg group compared to the non-Tg group in several brain regions. Most ROIs defined by the mouse brain atlas were not significantly different between the two groups.Conclusion We found increased microvascular indices of VSI and mVD in the Tg mice, reflecting microvascular disruption in the brain, which may be related to damages of the neurovascular unit in AD caused by cerebral amyloid angiopathy.Clinical Relevance / Application: To date, few studies have investigated the microvascular injuries of the AD brain using MRI. We suggest that investigation of cerebral microvasculature using a high-field MRI in AD would be worthwhile to elucidate the pathophysiology of cerebral amyloid angiopathy in this disease. Indeed, microvascular MRI can be a promising imaging tool for investigating early diagnosis and monitoring treatment in AD.

Objective Chemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia. Materials and methods Our institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTRasym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves. Results Amine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTRasym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTRasym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91. Conclusion CEST MRI potentially allows noninvasive image alterations in the Alzheimer's disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

Background: Longitudinal changes of brain metabolites during a functional stimulation are unknown in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) subjects. Objective: This study was to evaluate the longitudinal changes of brain metabolites using proton magnetic resonance spectroscopy (1H MRS) in response to treatment during a memory task in the subjects of cognitive normal (CN), aMCI, and AD. Methods: We acquired functional magnetic resonance spectroscopy (fMRS) data from 28 CN elderly, 16 aMCI and 12 AD subjects during a face-name association task. We measured fMRS metabolite ratios over 24 months in the 8-month apart, determined the temporal changes of the metabolites, and evaluated the differences among the three groups under the three different conditions (base, novel, repeat). Results: The results of comparisons for the three subject groups and the three-time points showed that tNAA/tCho and tCr/tCho were statistically significant among the three subject groups in any of the three conditions. The dynamic temporal change measurements for the metabolites for each condition showed that Glx/tCho and Glu/tCho levels at the third visit increased significantly compared with in the first visit in the novel condition in the AD group. Conclusion: We found declines in tNAA/tCho and tCr/tCho in the aMCI and AD subjects with increasing disease severity, being highest in CN and lowest in AD. The Glx/tCho level increased temporally in the AD subjects after they took an acetylcholine esterase inhibitor. Therefore, Glx may be suitable to demonstrate functional recovery after treatment.

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.

Objective: The study aimed to investigate exchangeable proton signals of Aβ proteins of the brains of Alzheimer’s disease (AD) model mice by using a chemical exchange-sensitive spin-lock (CESL) MR imaging technique. Method: Eight non-transgenic (Tg) mice (5 young and 3 old) and twelve Tg-APPswe/PSdE9 mice (5 young and 7 old) were used in this study. CESL Z-spectra were obtained by using two saturation powers, which were ω1 = 25 Hz with TSL = 3.0 s and ω1 = 500 Hz with TSL = 150 ms, at 71 offsets with uneven intervals between the offset frequencies at Ω = ±7.0 ppm at a 9.4-T animal MRI system. For Zspectrum analyses, regions of interest (ROIs) were drawn in the cortex, hippocampus, and thalamus of both hemispheres. Magnetization transfer ratio asymmetry (MTRasym) curves were obtained from the Zspectra. The Mann-Whitney test was used to compare the MTRasym values between the Tg and non-Tg mice for each offset frequency and for each ROI. Results: The water saturation width of the full Z-spectrum was narrow with the 25-Hz saturation power, but relatively broad with the 500-Hz saturation power. With the 25-Hz CESL saturation power, most of the MTRasym values were negative for 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the MTRasym values were significantly different between the control and Tg groups only in the left thalamus region at 3.5 ppm offset (p=0.0487). The MTRasym values were -6% to -7% for both 3.5 and 3.0 ppm, but less than -2% for both 2.0 and 0.9 ppm. With 500-Hz CESL saturation power, all the MTRasym values were positive for the 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the MTRasym values were not significantly different between the control and Tg groups at all ROIs and at all offset frequencies. However, a trend towards a significant difference was observed between the control and Tg groups in the right cortex at 3.5 ppm (p=0.0578). The MTRasym values were 6% to 9% for 3.5, 3.0, and 2.0 ppm, but less than 2% for 0.9 ppm. Conclusion: In an in-vivo AD model experiment, MTRasym values increased with the high saturation power than with the low saturation power. The MTRasym values were not significantly different, except in the left thalamus region at 3.5 ppm offset. The CESL technique should be further developed to enable its application in the brain of patients with neurodegenerative diseases.

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer’s disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. The results of voxel-based multiple regression analysis showed that blood levels of CypA, HO-1, and IRE1 were correlated with GMV on brain magnetic resonance imaging (MRI) in the entire population (p = 0.0005). The three serum protein levels were correlated with GMV of signature AD regions in the population as a whole. CypA values increased with increasing GMV in the occipital gyrus (r = 0.387, p &lt, 0.0001) and posterior cingulate (r = 0.196, p = 0.034). HO-1 values increased with increasing GMV at the uncus (r = 0.307, p = 0.0008), lateral globus pallidus and putamen (r = 0.287, p = 0.002), and hippocampus (r = 0.197, p = 0.034). IRE1 values decreased with increasing GMV at the uncus (r = −0.239, p = 0.010) and lateral globus pallidus and putamen (r = −0.335, p = 0.0002). Associations between the three serum protein levels and regional GMV indicate that the blood levels of these biomarkers may reflect the pathological mechanism of AD in the brain.

Purpose: Although a number of studies have focused on finding anatomical regions in which iron concentrations are high, no study has been conducted to examine the overall variations in susceptibility maps of Alzheimer’s disease (AD). The objective of this study, therefore, was to differentiate AD from cognitive normal (CN) and mild cognitive impairment (MCI) using a texture analysis of quantitative susceptibility maps (QSMs). Methods: The study was approved by the local institutional review board, and informed consent was obtained from all subjects. In each participant group—CN, MCI, and AD—18 elderly subjects were enrolled. A fully first-order flow-compensated 3D gradient-echo sequence was run to obtain axial magnitudes and phase images and to produce QSM data. Sagittal structural 3D T1-weighted (3DT1W) images were also obtained with the magnetization-prepared rapid acquisition of gradient-echo sequence to obtain brain tissue images. The first- and second-order texture parameters of the QSMs and 3DT1W images were obtained to evaluate group differences using a one-way analysis of covariance. Results: For the first-order QSM analysis, mean, standard deviation, and covariance of signal intensity separated the subject groups (F = 5.191, p = 0.009). For the second-order analysis, angular second moment, contrast, and correlation separated the subject groups (F = 6.896, p = 0.002). Finally, a receiver operating characteristic curve analysis differentiated MCI from CN in white matter on the QSMs (z = 3.092, p = 0.0020). Conclusions: This was the first study to evaluate the textures of QSM in AD, which overcame the limitations of voxel-based analyses. The QSM texture analysis successfully distinguished both AD and MCI from CN and outperformed the voxel-based analysis using 3DT1-weighed images in separating MCI from CN. The first-order textures were more efficient in differentiating MCI from CN than did the second-order.

Influenza infection increases the risk of ischemic stroke. Here, we represent a case of a 32year-old female who presented with acutely developed altered mental status after influenza A infection. The clinical manifestation and initial lesion on brain DWI mimicked top of basilar syndrome, but without an arterial occlusion or stenosis. Follow-up neuro imaging analysis suggested cerebral venous infarction. It is valuable to report this case of venous infarction in a healthy young adult, as an uncommon complication of adult influenza infection.

Alzheimer&rsquo, s disease (AD) is the most common type of dementia. AD involves major pathologies such as amyloid-&beta, (A&beta, ) 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 A&beta, deposition and memory loss in AD. Low-dose ionizing radiation (LDIR) is known to ameliorate A&beta, 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 A&beta, 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 A&beta, 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 A&beta, induced neuroinflammation by promoting M2 polarization via TREM2 expression, and has beneficial effects in the AD-related pathology such as A&beta, deposition and memory loss.

Address for correspondence Won Chul Shin, MD, PhD Department of Neurology, Kyung Hee University College of Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, Korea Tel: +82-2-440-6166 Fax: +82-2-440-7262 E-mail: shin1chul@gmail.com Objectives: Obstructive sleep apnea-hypopnea syndrome (OSAHS) and insomnia are two of the most common sleep disorders in the general population. Because OSAHS patients with insomnia may have difficulty in adapting to the sleep breathing medical equipment, it is necessary to pay special attention to the diagnosis and treatment of comorbid insomnia. This study is to investigate the emotion and personality in OSAHS patients with insomnia complaints by using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Methods: We reviewed the results of the standardized questionnaires assessing sleep-related variables, MMPI, and polysomnographic findings of the patients diagnosed as OSAHS. Results: 145 subjects were 49.05±11.83 years of age. The mean Respiratory Disturbance Index was 33.57±19.91 and the mean score of Insomnia Severity Index (ISI) was 11.52±6.49. The mean scores of the Beck Depression Inventory (BDI) and MMPI-2 were within normal ranges. We divided the patients into two groups based on the scores of the ISI, OSAHS with insomnia (n=109) and OSAHS without insomnia (n=36). OSAHS patients with insomnia symptoms had significantly higher scores of hypochondriasis, hysteria, psychasthenia, schizophrenia, paranoia and psychopathic deviate scales and BDI than those without insomnia. Conclusions: Our results suggest that insomnia complaints are very common in OSAHS patients and the psychological problems are more frequently found in OSAHS patients with insomnia symptom than those without it. J Sleep Med 2015;12(2):59-63

Our goal was to investigate whether three-dimensional (3D) double inversion recovery (DIR) images can show alterations of gray matter volume (GMV) between Alzheimer's disease (AD) patients and nondemented controls and to compare alterations of GMV between groups using DIR images and those using 3D T1-weighted (T1W) images. We included 25 subjects with mild or probable AD, 25 subjects with amnestic mild cognitive impairment (MCI), and 25 elderly cognitively normal (CN) subjects. Group differences in GMV among CN, MCI, and AD patients were tested by voxel-wise, one-way ANOVA. Additional region-of-interest-based comparisons of GMV differences among the three groups for DIR and T1WI were performed using ANCOVA. Finally, ROC curve analysis was performed. In the AD group compared with the CN and MCI groups, GMV was decreased in both DIR and T1W images. However, the areas showing GMV loss were larger in DIR images compared to those in T1W images. Amygdala had the highest area under curve value for both DIR and T1W images. DIR images were sensitive for identifying GMV loss in patients with AD compared with MCI and CN subjects and areas showing GMV loss identified with DIR were extended to more brain areas than those identified with T1W. With DIR, amygdala GMV is the most sensitive in differentiating between subject groups.

We investigated the frequency and clinical significance of diagonal earlobe crease (DELC) in cognitively impaired patients using imaging biomarkers, such as white matter hyperintensities (WMH) on MRI and amyloid-β (Aβ) PET. A total of 471 cognitively impaired patients and 243 cognitively normal (CN) individuals were included in this study. Compared with CN individuals, cognitively impaired patients had a greater frequency of DELC (OR 1.6, 95% CI 1.1–2.2, P = 0.007). This relationship was more prominent in patients with dementia (OR 1.8, 95% CI 1.2–2.7, P = 0.002) and subcortical vascular cognitive impairment (OR 2.4, 95% CI 1.6–3.6, P P

The aim of this study was to evaluate the efficacy of acupuncture and bee venom acupuncture (BVA) for idiopathic Parkinson's disease (IPD) through a sham-controlled trial. We also investigated whether there is a sustained therapeutic effect by completing follow-up assessments after treatment completion.A single center, double-blind, three-armed randomized controlled trial.This study was performed at a university hospital in Seoul, Republic of Korea.Seventy-three (73) patients with IPD were the subjects. They were randomly assigned to the active treatment group, sham treatment group, or conventional treatment group.The active treatment group received acupuncture and BVA and the sham group received sham acupuncture and normal saline injections, twice a week for 12 weeks. The conventional treatment group maintained anti-parkinsonian drugs without additional intervention.The Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III score, postural instability and gait disturbance (PIGD) score, gait speed and number, Parkinson's Disease Quality of Life Questionnaire, Beck Depression Inventory, and postural stability at baseline and at 12, 16, and 20 weeks.Sixty-three (63) patients provided a complete data of assessments, including a final follow-up. After 12 weeks of treatment, a significant difference was observed between the active treatment group and the conventional treatment group. After the end of the treatment, the treatment effects were maintained significantly in the active treatment group only.It is suggested that the combined treatment of acupuncture and BVA might be safe and useful adjunctive treatment for patients with IPD.

Address for correspondence Won Chul Shin, MD, PhD Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 892 Dongnam-ro, Gangdong-gu, Seoul 134-727, Korea Tel: +82-2-440-6166 Fax: +82-2-440-7262 E-mail: shinwc@khu.ac.kr Objectives: The polysomnographic hallmark of rapid eye movement (REM) sleep behavior disorder (RBD) is loss of muscle atonia during REM sleep; REM sleep without atonia (RSWA). However, the International Classification of Sleep Disorders (ICSD) criteria did not suggest optimized diagnostic value of RSWA and how to score muscle activity during REM sleep. Many previous studies have been tried to figure out the objective quantitative cut-off values of RSWA. We investigated RSWA in Korean RBD patients compared with normal control, to quantify the cut-off value in diagnosis of RBD, using both manual and computer-assisted scoring methods (REM atonia index, RAI). Methods: We retrospectively analyzed polysomnography and clinical data of 40 patients, 10 age-matched controls by ICSD-3 criteria. The quantitative analysis of chin electromyography density during REM sleep was done by both manual and computerized method. The RSWA and RAI were compared within two groups. Results: In computerized method, the mean RAI of RBD patient was 0.66±0.20, and 0.93±0.38 in control group (p

Introduction Mild cognitive impairment (MCI) is distinguishable from the memory loss associated with normal aging and may represent an early stage of Alzheimer's disease. This study sought to determine whether jaw-tapping could be a useful exercise to improve memory function by observing changes in brain activity. Methodology Twelve subjects with subjective memory complaints (SMC group) and thirteen MCI patients (MCI group) participated in a prospective functional magnetic resonance imaging (fMRI) study. All subjects performed jaw-tapping and n-back memory tasks during blood oxygen level dependent (BOLD) fMRI. Measurements were made before and after home practice of the jaw-tapping exercise for 4 weeks. Pre- and post-test fMRI data were analyzed using statistical parametric maps of brain activation. Results The SMC and the MCI groups showed improvement in the memory task after 4 weeks of jaw-tapping training. In the SMC group, more brain regions were activated overall, including the prefrontal, temporal, and precuneus regions related to memory function. Although fewer brain regions were activated in the MCI group compared to the SMC group, brain activity increased in the MCI group after 4 weeks of training. Conclusion Jaw-tapping movement could be a useful exercise for improving memory and cognitive function in elderly people with memory disturbance by stimulating brain regions related to these functions.

Although a number of studies have focused on finding anatomical regions in which iron concentrations are high, no study has been conducted to examine the overall variations in susceptibility maps of Alzheimer's disease (AD). The objective of this study, therefore, was to differentiate AD from cognitive normal (CN) and mild cognitive impairment (MCI) using a texture analysis of quantitative susceptibility maps (QSMs).The study was approved by the local institutional review board, and informed consent was obtained from all subjects. In each participant group-CN, MCI, and AD-18 elderly subjects were enrolled. A fully first-order flow-compensated 3D gradient-echo sequence was run to obtain axial magnitudes and phase images and to produce QSM data. Sagittal structural 3D T1-weighted (3DT1W) images were also obtained with the magnetization-prepared rapid acquisition of gradient-echo sequence to obtain brain tissue images. The first- and second-order texture parameters of the QSMs and 3DT1W images were obtained to evaluate group differences using a one-way analysis of covariance.For the first-order QSM analysis, mean, standard deviation, and covariance of signal intensity separated the subject groups (F = 5.191, p = 0.009). For the second-order analysis, angular second moment, contrast, and correlation separated the subject groups (F = 6.896, p = 0.002). Finally, a receiver operating characteristic curve analysis differentiated MCI from CN in white matter on the QSMs (z = 3.092, p = 0.0020).This was the first study to evaluate the textures of QSM in AD, which overcame the limitations of voxel-based analyses. The QSM texture analysis successfully distinguished both AD and MCI from CN and outperformed the voxel-based analysis using 3DT1-weighed images in separating MCI from CN. The first-order textures were more efficient in differentiating MCI from CN than did the second-order.

BACKGROUND The metabolite response during a memory task in Alzheimer's disease (AD) patients is unknown. OBJECTIVE To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS). METHODS This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups. RESULT Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p < 0.001), the novel condition (DF = 3, F = 6.945, p < 0.001), and the repeat condition (DF = 3, F = 7.127, p < 0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD. CONCLUSION Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD.

This study aimed to explore the effectiveness of both acupuncture and bee venom acupuncture as adjuvant therapies for idiopathic Parkinson’s disease. We recruited 43 adults with idiopathic Parkinson’s disease who had been on a stable dose of antiparkinsonian medication for at least 1 month. They were randomly assigned to 1 of 3 groups: acupuncture, bee venom acupuncture, or control. All participants were assessed using the Unified Parkinson’s Disease Rating Scale, the Parkinson’s Disease Quality of Life Questionnaire, the Beck Depression Inventory, the Berg Balance Scale, and the time and number of steps required to walk 30 m. Treatment groups underwent stimulation of 10 acupuncture points using acupuncture or bee venom acupuncture twice a week for 8 weeks. The initial assessment was repeated at the completion of treatment. The control group did not receive any treatment. Participants in the bee venom acupuncture group showed significant improvement on the Unified Parkinson’s Disease Rating Scale (total score, as well as parts II and III individually), the Berg Balance Scale, and the 30 m walking time. When compared to the control group, the bee venom acupuncture group experienced significantly greater improvement on the Unified Parkinson’s Disease Rating Scale. In the acupuncture group, the Unified Parkinson’s Disease Rating Scale (part III and total scores) and the Beck Depression Inventory showed significant improvement. The control group showed no significant changes in any outcome after 8 weeks. In this pilot study, both acupuncture and bee venom acupuncture showed promising results as adjuvant therapies for Parkinson’s disease.

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). 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. 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. 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.

Cognitive decline following posterior cerebral artery infarction (PCAI) is associated with lesions in the occipital lobe that extend into the parahippocampus or the splenium. We investigated patterns of neuropsychological deficits, including those causing executive dysfunction, associated with isolated lesions of the occipital lobe and with extensive lesions of the occipital lobe that extended into the splenium or the posterior ventral temporal lobes including the parahippocampus and fusiform gyrus. Eleven patients with unilateral PCAI involving the cerebral cortex and one patient with an occipital hemorrhage were selected for inclusion in this study. The mean age of the patients was 68.50 ± 7.94 years and their mean level of education was 8.58 ± 4.12 years. Four patients had isolated occipital lobe lesions and eight had lesions in either the splenium or the posterior ventral temporal lobe in addition to the occipital lobe. Whereas three of four patients with isolated occipital lobe lesions had left-sided lesions, only three of the eight patients with extended occipital lesions had left-sided lesions. The patients underwent a standardized battery of neuropsychological tests. The patients with occipital injuries in addition to splenial or posterior ventral temporal lobe injuries demonstrated performance decline across diverse cognitive domains, including memory (eight of eight), visuospatial function (eight of eight), executive function (seven of eight), language-related function (four of eight) and attention (one of eight). In contrast, memory impairment (three of four patients) was the only area in which patients with isolated occipital lobe lesions demonstrated decline in performance. Our findings suggest that strokes in the territory of the posterior cerebral artery are frequently associated with executive dysfunction. Injuries involving the splenium or posterior ventral temporal lobe in addition to the occipital lobe lead to more diverse neuropsychological impairments than do isolated occipital lobe injuries alone.

We describe a patient with an intraspinal paraganglioma who presented with normal pressure hydrocephalus. A 70-year-old man presented with a 6-month history of gait disturbance and cognitive dysfunction. Computed tomography of the brain and magnetic resonance imaging of the spine revealed communicating hydrocephalus and a spinal mass at the T12-L1 level which proved to be a paraganglioma of the filum terminale. Radioisotope cisternography revealed a severe delay in cerebrospinal fluid circulation. Symptoms related to communicating hydrocephalus resolved after tumor resection.