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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-β (Aβ) 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, Aβ42/Aβ40 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between plasma amyloid-β (Aβ) levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform. Methods: We prospectively recruited 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid positron emission tomography (PET) scanning, and detailed neuropsychological tests. Patients were classified into a normal control (NC, n = 25) or Alzheimer's disease (AD, n = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results. Results: The plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid PET positivity by receiver operating characteristic curve analysis [area under the curve of 0.952 (95% confidence interval, 0.892–1.000)]. Although there were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups, higher levels of plasma Aβ42/40 were negatively correlated only with verbal and visual memory performance. Conclusion: Our results demonstrated that plasma Aβ analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cerebral small vessel disease is the most common cause of subcortical vascular dementia (SVaD). Unfortunately, conventional imaging techniques do not always demonstrate the microvascular pathology that is associated with small vessel disease. The purpose of this study was to evaluate the changes in the microvascular structure of SVaD and to identify how the microvascular changes in vessel size, detected with imaging, affect the gray matter. Methods: Ten SVaD patients and 12 healthy controls underwent vessel size imaging with gradient-echo and spin-echo sequences before and after contrast agent injection. Four microvessel index maps, including total blood volume fraction (BVf), mean vessel density (Q), mean vessel diameter (mVD), and vessel size index (VSI) were calculated. ROI value of each microvessel parameter was compared between SVaD patients and controls. Voxel-wise comparison of microvessel parameters was also performed to assess the regional difference. The relationship between the microvessel parameters in white matter and total gray matter volume (TGV) were assessed. Results: Both mVD and VSI were significantly different between the SVaD and controls in the ROI-based comparisons (unpaired t -test, p < 0.05). mVD and VSI were significantly increased in the SVaD group at the subcortical, periventricular white matter, basal ganglia, and thalami compared with the controls (FDR corrected, p < 0.05). VSI in the white matter areas were significantly negatively correlated with TGV (r = −0.446, p < 0.05). Conclusions: The increase of mVD and VSI in SVaD patients reflects the damage of the microvessels in the white matter, and these changes may lead to the damage of the gray matter. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported increased concentrations of metallic ions and imbalanced Na+ and K+ ions in patients with Alzheimer's disease (AD) and the increased mobility of protons by microstructural disruptions in AD. The purposes of this study were: 1)to apply a high‐frequency conductivity (HFC) mapping technique using a clinical 3T MRI system and 2)to compare HFC values among participant groups. Method: This prospective study included 74 participants (23 AD patients, 27 amnestic mild cognitive impairment (MCI) patients, and 24 cognitively normal (CN) elderly people) to explore the clinical application of HFC mapping in the brain. For the brain MREPT images, a multi‐echo turbo spin‐echo pulse sequence was used. A homemade software was used to map the HFC at the Larmor frequency of 128 MHz at 3T. We performed statistical analyses to 1) compare HFC maps between the three participant groups and 2) to evaluate the association of HFC maps with Mini‐Mental State Examination (MMSE) scores. Result: The HFC value was higher in the AD group than in the CN and MCI groups. MMSE scores were negatively associated with HFC values, but age was positively associated with HFC values. The HFC value in the insula has a high area under the 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 GMV in hippocampus (SE = 79, SP = 83, AUC = 0.880, p < 0.0001). Conclusion: HFC 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. [ABSTRACT FROM AUTHOR]

Background: Although definite diagnosis for Creutzfeldt‐Jakob disease(CJD) requires tissue confirmation, diffusion‐weighted imaging (DWI) of the brain has an important role in the diagnosis of CJD. Also elevated CSF total tau (t‐tau) is considered as an useful CJD biomarker revealing neuro‐axonal damage although it is not specific for CJD. In this study, we attempted to find out the association between DWI abnormality and CSF t‐tau in CJD patients. Method: We retrospectively analyzed the medical records reported as human prion disease.The patients who had been diagnosed and reported as human prion disease to Korea Disease Control and Prevention Agency (KDCA) by medical institutions in South Korea during the period of January 1, 2019 to December 31, 2019 were included in this study. The clinical information of the reported patients had been reviewed by a clinical review committee of KDCA for CJD and the patients who had fulfilled the criteria for probable CJD were evaluated for clinical, radiological, and laboratory findings. Result: A total of 186 patients had been reported as suspected human prion disease during the one‐year period and 53 patients who satisfied the criteria for human prion disease were included in the analysis. The most common clinical presentation was cognitive change, followed by cerebellar dysfunction and extrapyramidal symptoms. Hyperintense lesions on DWI were observed in 52 patients (98%). The involvement of neocortex was observed in almost all patients (98%) and asymmetrical and bilateral hyperintensities on DWI were common. Among neocortex, the most commonly involved region was parietal lobe, followed by frontal lobe, temporal lobe, and occipital lobe. DWI abnormality in striatum and/or thalamus was observed in 65.3% of patients. CSF t‐tau was elevated in sporadic CJD patients (8998.3±11903.7 pg/ml) There was no significant association between the extent of the lesions on DWI and CSF t‐tau. Conclusion: In this study,most of the patients with probable CJD showed DWI abnormality mainly on neocortex (parietal > frontal > temporal > occipital) but the association between the pattern of DWI abnormality and the level of CSF t‐tau was not observed. [ABSTRACT FROM AUTHOR]

Objective: 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. Design: A single center, double-blind, three-armed randomized controlled trial. Settings/Location: This study was performed at a university hospital in Seoul, Republic of Korea. Subjects: 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. Interventions: 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. Outcome measures: 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. Results: 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. Conclusions: It is suggested that the combined treatment of acupuncture and BVA might be safe and useful adjunctive treatment for patients with IPD. [ABSTRACT FROM AUTHOR]

Background: Conventional MRI techniques cannot demonstrate microvascular alterations in mild and moderate 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. Method: Eleven patients with AD and 11 non‐AD controls were included in this cross‐sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a 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 the mini‐mental state examination (MMSE) score. Result: Compared with the non‐AD group, BVf was significantly increased in the AD group at the parahippocampal gyrus (p = 0.033), gray matter area (p = 0.008), and white matter area (p = 0.010). MvWI was also significantly increased in the AD group at the hippocampus (p = 0.010), parahippocampal gyrus (p = 0.010), precuneus (p = 0.045), and globus pallidus (p = 0.008). Both mVD and VSI were only significantly decreased in the AD group at the white matter hyperintensity (WMHI) area (p = 0.045 with mVD; p = 0.033 with VSI). BVf and MvWI were significantly positively correlated with age at some areas. VSI was significantly positively correlated with MMSE at caudate (rho = 0.475/ p = 0.030) and corpus callosum (rho = 0.435/ p = 0.049). Conclusion: Microvascular index was a useful non‐invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as vessel constriction and increasing blood volume fraction. It was associated with MMSE score. [ABSTRACT FROM AUTHOR]

Background: Developing an imaging technique to map myelin changes in the brain within a short scan time is needed due to the inability of Alzheimer's disease (AD) patients to remain motionless during MRI scanning. Purpose: 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. Method: In this prospective study from March 2019 to October 2021, the participants were allocated as follows: 29 individuals were assigned to the cognitively normal (CN) elderly group (mean ± SD, 73 ± 5 years, 16 females), 32 participants were assigned to the MCI group (74 ± 5 years, 21 females), and 31 patients were assigned to the AD group (74 ± 6 years, 26 females). 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. Result: A total of 92 participants were evaluated. The AD group showed a reduced apparent MWF compared to the CN and MCI groups. Moreover, the MWF was decreased with age and positively correlated with Mini‐Mental State Examination scores. The largest AUC value (0.799) was in the corpus callosum and used to classify the CN and AD groups using the apparent MWF. Conclusion: 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. Funding: The research was supported by the National Research Foundation of Korea (NRF) grant funded by Ministry of Science and ICT (No. 2020R1A2C1004749, GHJ), Republic of Korea. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the relationship between the level of plasma amyloid‐β (Aβ) and neuropsychological performance in patients with cognitive decline, classified according to amyloid PET positivity using a highly sensitive nano‐biosensing platform. Method: A total of 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid PET scanning, and detailed neuropsychological tests were recruited in this study. The participants comprised 20 patients with subjective cognitive decline, 7 with amnestic mild cognitive impairment, and 17 with probable AD dementia. Patients were classified into a normal control (NC, N = 25) or Alzheimer's disease (AD, N = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results. Result: The plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid positivity by receiver operating characteristic curve analysis. There were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups. However, in multivariate regression analysis, upon inclusion of age, education, vascular risk factors, and apolipoprotein E ε4 status, higher levels of plasma Aβ42/40 showed significant negative correlations with verbal and visual memory performance, including immediate recall, delayed recall, and recognition tests. Conclusion: We suggest that our study might have clinical significance because plasma Aβ analysis using a highly sensitive nano‐biosensing platform could not only be a useful non‐invasive method for diagnosing AD, but also showed a significant association with memory performance in patients with cognitive decline. Further investigations with a larger sample size are necessary to clarify the possible relevance of plasma Aβ as a blood‐based biomarker for precise AD diagnosis. [ABSTRACT FROM AUTHOR]

Background: We aimed to analyze plasma amyloid‐β (Aβ) using a highly sensitive nano‐biosensing platform to demonstrate the possibility of precise cerebral amyloid angiopathy (CAA) diagnosis in participants classified according to amyloid PET positivity and the neuroimaging criteria for CAA. Method: A total of 25 normal controls (NC) and 19 patients with Alzheimer's disease (AD), which were further classified into the CAA− and CAA+ groups according to the modified Boston criteria were recruited in this study. All participants underwent plasma Aβ analysis using a highly sensitive nano‐biosensing platform, amyloid PET scanning, and detailed neuropsychological testing. Result: The average signal levels of plasma Aβ42/40 differed significantly between the NC and AD groups, and the CAA+ group exhibited significantly higher plasma Aβ40 signal levels than the CAA− group in both NC and AD groups. The concordance between the plasma Aβ40 signal level and the neuroimaging criteria for CAA was nearly perfect. Higher plasma Aβ40 signal levels were significantly associated with the presence of CAA based on the regression analyses, and the neuroimaging pattern analysis partly supported this result. Conclusion: Our findings suggest that measuring plasma Aβ40 using a highly sensitive nano‐biosensing platform could be a useful non‐invasive diagnostic method for detecting CAA. [ABSTRACT FROM AUTHOR]

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 gradientecho 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The heme oxygenase‐1 (HO‐1) is known as up‐regulator in AD. The peptidylprolyl isomerase A (PPIA) (also known as cyclophilin A, CyPA) provides protection of neurons against copper‐mediated oxidative stress. The inositol‐requiring enzyme 1 (IRE1) is a major stress transducer in endoplasmic reticulum (ER) stress and abnormal protein aggregation. There is no study to evaluate the relationship between gray matter volume (GMV) loss and the three blood‐based biomarkers. Therefore, in this study, we evaluated the relationship between imaging biomarker by GMV changes and blood biomarkers by plasma levels of HO‐1, PPIA, and IRE1 in the groups of cognitively normal (CN), amnestic mild cognitive impairment (MCI), and AD participants. Method: We obtained MRI and plasma levels of the three blood biomarkers from 45 CN, 34 amnestic MCI, and 39 AD. To assess the relationship between GMV or WMV loss and the three blood biomarkers, the voxel‐based multiple regression analysis was performed for using all participant data. In addition, region‐of‐interest (ROI)‐based analysis was performed to determine correlations between ROI‐based brain tissue volumes and plasma biomarkers. To investigate the relationship between GMV or WMV at each ROI and the plasma levels of HO‐1, PPIA, and IRE1, we performed the Pearson correlation analyses. Result: The CypA value was significantly positively correlated with MMSE scores. The HO‐1 value was significantly negatively correlated with age, but was positively correlated with the K‐MMSE score. The IRE1 value was significantly positively correlated with age, but was negatively correlated with K‐MMSE scores. GMV was positively correlated with CypA and HO‐1, but negatively correlated with IRE1. Conclusion: Our study demonstrates that subjects with AD have lower circulating levels of HO‐1 than subjects with MCI and the plasma HO‐1 levels were positively associated with the global GMV. This also shows that subjects with AD have lower circulating levels of CyPA than cognitively normal control and the plasma CyPA levels were positively associated with the GMV whereas subjects with AD have higher circulating levels of IRE1 than subjects with MCI and normal control. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate efficient, systematic management of the Korean police and to examine the status and prevention of musculoskeletal disorders in Korean police officers. For police officers in special working environments, the importance of basic data is emphasized for human resources (HR) management and the prevention of industrial hazards from an industrial health care perspective. This study was conducted on police officers who visited the national police hospital and who underwent x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) for the diagnosis of musculoskeletal disorders. The results revealed that examinations for the lower extremities and spine were most frequently conducted using x-ray, CT, and MRI. In particular, knee and lumbar examinations were most frequently conducted among all lower extremity and spine examinations, respectively. [ABSTRACT FROM PUBLISHER]

Influenza infection increases the risk of ischemic stroke. Here, we represent a case of a 32 year-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Few studies have examined white matter hyperintensities (WMH) along the cognitive continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and Alzheimer’s disease (AD). The aims of our study were to explore relationships between the extent and location of WMH and disease severity along the cognitive continuum and to determine whether differences in the distribution of WMH could be predictive of specific patterns of cognitive impairment. We compared cognitive function, vascular risk factors, and regional (frontal lobe, parieto-occipital [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24 age-matched and education-matched normal controls. A quantitative volumetric method was applied to measure WMH burden. Total and regional WMH burdens, except for those in the temporal lobe, were significantly correlated with age (p <0.01). We found a trend toward increasing WMH volume with disease severity, higher in AD than in sd-aMCI and lowest in the controls. Total WMH volume was associated with the global cognitive test score. In multiple linear regression analysis, PV WMH volume, but not deep WMH volume, strongly predicted performances on the Controlled Oral Word Association test and the Color Word Stroop test after adjusting for important demographic variables. Only PO WMH volume was a significant predictor of a cognitive test score when frontal and temporal WMH volumes were simultaneously entered into the regression model. The extent and distribution of WMH, especially in the PV and PO regions, were associated with disease severity and reduced cognition. [Copyright &y& Elsevier]

Abstract: 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±7.94years and their mean level of education was 8.58±4.12years. 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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 < 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. [ABSTRACT FROM AUTHOR]

A 62-year-old man with lung cancer underwent a right lower bilobectomy of the lung. After resection, we insufflated air through the diaphragm into the peritoneal cavity, and sudden cardiac arrest developed in the patient. A large number of air bubbles were aspirated from the heart and great vessels, and the patient recovered after resuscitation. However, he remained with a left sensory deficit, a left homonymous hemianopia, and left hemiparesis. A brain computed tomographic scan revealed an acute ischemic lesion in the right parieto-occipital area. Our case shows that an air embolism is a possible complication of artificial intraoperative pneumoperitoneum after pulmonary resection. [Copyright &y& Elsevier]

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

A correction to the article "Glutamine and Glutamate Complex, as Measured by Functional Magnetic Resonance Spectroscopy, Alters During Face-Name Association Task in Patients with Mild Cognitive Impairment and Alzheimer's Disease" that was published in the previous issue is presented.