Prediction of hemifacial spasm re-appearing phenomenon after microvascular decompression surgery in patients with hemifacial spasm using dynamic susceptibility contrast perfusion MRI.

Objective: Hemifacial spasm (HFS) is treated by a surgical procedure called microvascular decompression (MVD). However, HFS re-appearing phenomenon after surgery, presenting as early recurrence, is experienced by some patients after MVD. Dynamic susceptibility contrast (DSC) perfusion MRI and two analytical methods: receiver operating characteristic (ROC) curve and machine learning, were used to predict early recurrence in this study. Methods: This study enrolled sixty patients who underwent MVD for HFS. They were divided into two groups: Group A consisted of 32 patients who had early recurrence, and Group B consisted of 28 patients who had no early recurrence of HFS. DSC perfusion MRI was undergone by all patients before the surgery to obtain the several parameters. ROC curve and machine learning methods were used to predict early recurrence using these parameters. Results: Group A had significantly lower relative cerebral blood flow (rCBF) than Group B in most of the selected brain regions, as shown by the region-of-interest (ROI)-based analysis. By combining three extraction fraction (EF) values at middle temporal gyrus, posterior cingulate, and brainstem, with age, using naive Bayes machine learning method, the best prediction model for early recurrence was obtained. This model had an area under the curve (AUC) value of 0.845. Conclusion: By combining EF values with age or sex using machine learning methods, DSC perfusion MRI can be used to predict early recurrence before MVD surgery. This may help neurosurgeons to identify patients who are at risk of HFS recurrence and provide appropriate postoperative care.

Oligomeric amyloid-ß targeted contrast agent for MRI evaluation of Alzheimer's disease mouse models.

Background: Oligomeric amyloid beta (oAß) is a toxic factor that acts in the early stage of Alzheimer's disease (AD) and may initiate the pathologic cascade. Therefore, detecting oAß has a crucial role in the early diagnosis, monitoring, and treatment of AD. Purpose: The purpose of this study was to evaluate MRI signal changes in different mouse models and the time-dependent signal changes using our novel gadolinium (Gd)-dodecane tetraacetic acid (DOTA)- ob5 aptamer contrast agent. Methods: We developed an MRI contrast agent by conjugating Gd-DOTA-DNA aptamer called ob5 to evaluate its ability to detect oAß deposits in the brain using MRI. A total of 10 control mice, 9 3xTg AD mice, and 11 APP/PS/Tau AD mice were included in this study, with the age of each model being 16 or 36 weeks. A T1-weighted image was acquired at the time points before (0 min) and after injection of the contrast agent at 5, 10, 15, 20, and 25 min. The analyses were performed to compare MRI signal differences among the three groups and the time-dependent signal differences in different mouse models. Results: Both 3xTg AD and APP/PS/Tau AD mouse models had higher signal enhancement than control mice at all scan-time points after injection of our contrast media, especially in bilateral hippocampal areas. In particular, all Tg AD mouse models aged 16 weeks showed a higher contrast enhancement than those aged 36 weeks. For 3xTg AD and APP/PS/Tau AD groups, the signal enhancement was significantly different among the five time points (0 min, 5 min, 10 min, 15 min, 20 min, and 25 min) in multiple ROI areas, typically in the bilateral hippocampus, left thalamus, and left amygdala. Conclusion: The findings of this study suggest that the expression of the contrast agent in different AD models demonstrates its translational flexibility across different species. The signal enhancement peaked around 15-20 min after injection of the contrast agent. Therefore, our novel contrast agent targeting oAß has the potential ability to diagnose early AD and monitor the progression of AD.

Increased extra-neurite conductivity of brain in patients with Alzheimer's disease: A pilot study.

The objectives of this study were to investigate how the extra-neurite conductivity (EC) and intra-neurite conductivity (IC) were reflected in Alzheimer's disease (AD) patients compared with old cognitively normal (CN) people and patients with amnestic mild cognitive impairment (MCI) and to evaluate the association between those conductivity values and cognitive decline. To do this, high-frequency conductivity (HFC) at the Larmor frequency was obtained using MRI-based electrical property tomography (MREPT) and was decomposed into EC and IC using information of multi-shell multi-gradient direction diffusion tensor images. This prospective single-center study included 20 patients with mild or moderate AD, 25 patients with amnestic MCI, and 21 old CN participants. After decomposing EC and IC from HFC for all participants, we performed voxel-based and regions-of-interest analyses to compare conductivity between the three participant groups and to evaluate the association with either age or the Mini-Mental State Examination (MMSE) scores. We found increased EC in AD compared to CN and MCI. EC was significantly negatively associated with MMSE scores in the insula, and middle temporal gyrus. EC might be used as an imaging biomarker for helping to monitor cognitive function.

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function.

BACKGROUND: Apolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis. OBJECTIVE: To predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods. METHODS: We recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE ε4 carriers and 52 noncarriers) and scanned them with three-dimensional (3D) T1-weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini-mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE ε4 carrier with different ML models. RESULTS: The best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone. CONCLUSION: Our results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE ε4 status and identifying individuals at risk of AD progression.

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea.

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS-cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC-cortex FC values positively correlated with the arousal, apnea, and apnea-hypopnea index in OSA patients. Alterations in ARAS-cortex FC were observed in OSA patients. The strength of LC-cortex noradrenergic FC was related to arousal or OSA severity in patients.

Efficacy of Kami Guibi-tang as an Add-On Therapy to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer's Disease: A Pilot Study.

Background: Kami Guibi-tang (KGT), a traditional Korean herbal medicine is mainly used to treat insomnia and nervousness. Acetylcholinesterase inhibitors (AChEIs) are the main treatments for mild Alzheimer's disease (AD), a degenerative brain disease. However, currently no drug can fundamentally treat AD or reverse the advanced cognitive decline. This clinical study explored the efficacy and safety of adding KGT to AChEI for cognitive function in mild AD. Methods: This was a pilot study for a larger randomized, double-blind, placebo-controlled trial. Participants between 55-90 years diagnosed with mild AD were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea. They were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary outcome was treatment efficacy, as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D). Changes in SNSB subscores were assessed as secondary outcomes. Safety parameters, including adverse events and abnormalities in blood tests, electrocardiograms, and brain magnetic resonance imaging were also monitored. Results: Between March 2018 and November 2020, seven participants each in the KGT group and the placebo group completed the 24-week trial. There were no significant changes in SNSB-D total or subindex scores for either group (p = 0.69 and 0.63, respectively), and no significant differences were observed between them (p=0.71). No adverse events related to KGT were reported. We also compared and analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment (aMCI) using protocol of this study. The aMCI group showed a significant improvement in the total SNSB-D score, especially in the memory domain, compared to the mild AD group (p = 0.04 and 0.02, respectively). The Korean Mini-Mental State Exam and Korean Instrumental Activities of Daily Living scores also significantly improved in the aMCI group (p = 0.01 and 0.02, respectively). Conclusions: Compared to placebo, adding KGT to AChEI did not significantly improve cognitive function in SNSB in patients with mild AD. We suggest that KGT would have a positive effect on patients with early stages of cognitive impairment such as aMCI. The findings could assist design larger, longer-term clinical trials of KGT use in elderly patients with mild AD. This study was registered in the Korean Clinical Trial Registry on December 26, 2017, with the CRIS approval number KCT0002904.

High frequency conductivity decomposition by solving physically constraint underdetermined inverse problem in human brain.

The developed magnetic resonance electrical properties tomography (MREPT) can visualize the internal conductivity distribution at Larmor frequency by measuring the B1 transceive phase data from magnetic resonance imaging (MRI). The recovered high-frequency conductivity (HFC) value is highly complex and heterogeneous in a macroscopic imaging voxel. Using high and low b-value diffusion weighted imaging (DWI) data, the multi-compartment spherical mean technique (MC-SMT) characterizes the water molecule movement within and between intra- and extra-neurite compartments by analyzing the microstructures and underlying architectural organization of brain tissues. The proposed method decomposes the recovered HFC into the conductivity values in the intra- and extra-neurite compartments via the recovered intra-neurite volume fraction (IVF) and the diffusion patterns using DWI data. As a form of decomposition of intra- and extra-neurite compartments, the problem to determine the intra- and extra-neurite conductivity values from the HFC is still an underdetermined inverse problem. To solve the underdetermined problem, we use the compartmentalized IVF as a criterion to decompose the electrical properties because the ion-concentration and mobility have different characteristics in the intra- and extra-neurite compartments. The proposed method determines a representative apparent intra- and extra-neurite conductivity values by changing the underdetermined equation for a voxel into an over-determined minimization problem over a local window consisting of surrounding voxels. To suppress the noise amplification and estimate a feasible conductivity, we define a diffusion pattern distance to weight the over-determined system in the local window. To quantify the proposed method, we conducted a simulation experiment. The simulation experiments show the relationships between the noise reduction and the spatial resolution depending on the designed local window sizes and diffusion pattern distance. Human brain experiments (five young healthy volunteers and a patient with brain tumor) were conducted to evaluate and validate the reliability of the proposed method. To quantitatively compare the results with previously developed methods, we analyzed the errors for reconstructed extra-neurite conductivity using existing methods and indirectly verified the feasibility of the proposed method.

Microvascular morphology alteration using relaxation rate change with gadolinium-based magnetic resonance imaging contrast agent in patients with Alzheimer's disease.

Background: Conventional magnetic resonance imaging (MRI) techniques cannot demonstrate microvascular alterations in mild Alzheimer's disease (AD). Thus, the diagnosis of microvascular pathology commonly relies on postmortem. The purpose of this study was to evaluate alterations of microvascular structures in patients with AD using a 3T clinical MRI system with a commercially available contrast agent. Methods: Eleven patients with AD and 11 cognitively normal (CN) controls were included in this cross-sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a Gadolinium (Gd)-based contrast agent injection were calculated from images obtained with a multi-echo turbo spin-echo sequence and multi-echo gradient-echo sequence to obtain microvascular index maps of blood volume fraction (BVf), mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), and microvessel-weighted imaging (MvWI). Two-sample t-test was used to compare those values between the two groups. Correlation analysis was performed to evaluate the relationship between those values and age. Results: BVfs at the corpus callosum and at the thalamus were significantly increased in the AD group (P=0.024 and P=0.005, respectively). BVf at the gray matter (P=0.020) and white matter area (P=0.012) were also significantly increased in the AD group compared with the CN group. MvWIs at the hippocampus and parahippocampal gyrus were significantly increased in the AD group compared with the CN group (P=0.020 and P=0.006, respectively). Voxel-based analysis showed both mVD and VSI were significantly decreased at the prefrontal lobe in the AD group. Q were not significant difference between CN and AD groups. MvWI were significantly positively correlated with age. Conclusions: Microvascular index was a useful non-invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as increasing BVf and microvessel-weighted.

Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.

This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.

Altered intrinsic brain functional network dynamics in moderate-to-severe obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can affect temporal fluctuations in brain activity during rest. Dynamic functional connectivity (dFC) captures the fluctuations in FC during the resting state. This study aimed to investigate differences in dFC between moderate-to-severe OSA patients and healthy controls using resting-state functional magnetic resonance imaging (fMRI) and sliding-window analysis. METHODS: Thirty-seven consecutive patients with moderate-to-severe OSA and 16 age- and sex-matched controls underwent resting-state fMRI in the morning following overnight polysomnography. The dynamics of aberrant FC between the groups and the correlation between the dynamics and clinical variables were evaluated. RESULTS: dFC analysis revealed two distinct connectivity states: hypoconnected (State I) and hyperconnected (State II). In OSA patients, State I occurred 34% more often than in the controls and the occurrence of State II was proportionally reduced. The time in State I positively correlated with the Pittsburg Sleep Quality Index score in the OSA patients. CONCLUSIONS: This study showed dFC alterations in moderate-to-severe OSA patients, which may serve as a novel physiological biomarker for OSA.

An aptamer-based magnetic resonance imaging contrast agent for detecting oligomeric amyloid-ß in the brain of an Alzheimer's disease mouse model.

The oligomeric amyloid-ß (oAß) is a reliable feature for an early diagnosis of Alzheimer's disease (AD). Therefore, the objective of this study was to demonstrate imaging of oAß deposits using our developed DNA aptamer called ob5 conjugated with gadolinium (Gd)-dodecane tetraacetic acid (DOTA) as a contrast agent for early diagnosis of AD using MRI. An oAß-specific aptamer was developed by amide bond formation and conjugated to Gd-DOTA MRI contrast agent and/or cyanine5 (cy5). We verified the performance of our new contrast agent with an AD mouse model using in vivo and ex vivo fluorescent imaging and animal MRI experiments. The presence of soluble Aß in 3xTg AD mice was detected using GdDOTA-ob5-cy5 probe ex vivo. Fluorescence intensities of the GdDOTA-ob5-cy5 contrast agent were high in the brains of 3xTg-AD mice, but relatively low in the brains of control mice. The GdDOTA-ob5 contrast agent had higher relaxivity than a clinically available contrast agent. T1-weighted MRI signals in 5-month-old 3xTg AD mice increased at 5 min, were prolonged until 10 min, then decreased 15 min after injecting the GdDOTA-ob5 contrast agent. Our targeted DNA aptamer GdDOTA-ob5 contrast agent could be potentially useful for validating the efficacy of a novel diagnostic contrast agent for selectively targeting neurotoxic oAß. It could ultimately be used for early diagnosis of AD.

Gray-white matter boundary Z-score and volume as imaging biomarkers of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) presents typically gray matter atrophy and white matter abnormalities in neuroimaging, suggesting that the gray-white matter boundary could be altered in individuals with AD. The purpose of this study was to explore differences of gray-white matter boundary Z-score (gwBZ) and its tissue volume (gwBTV) between patients with AD, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) elderly participants. Methods: Three-dimensional T1-weight images of a total of 227 participants were prospectively obtained from our institute from 2006 to 2022 to map gwBZ and gwBTV on images. Statistical analyses of gwBZ and gwBTV were performed to compare the three groups (AD, MCI, CN), to assess their correlations with age and Korean version of the Mini-Mental State Examination (K-MMSE), and to evaluate their effects on AD classification in the hippocampus. Results: This study included 62 CN participants (71.8 ± 4.8 years, 20 males, 42 females), 72 MCI participants (72.6 ± 5.1 years, 23 males, 49 females), and 93 AD participants (73.6 ± 7.7 years, 22 males, 71 females). The AD group had lower gwBZ and gwBTV than CN and MCI groups. K-MMSE showed positive correlations with gwBZ and gwBTV whereas age showed negative correlations with gwBZ and gwBTV. The combination of gwBZ or gwBTV with K-MMSE had a high accuracy in classifying AD from CN in the hippocampus with an area under curve (AUC) value of 0.972 for both. Conclusion: gwBZ and gwBTV were reduced in AD. They were correlated with cognitive function and age. Moreover, gwBZ or gwBTV combined with K-MMSE had a high accuracy in differentiating AD from CN in the hippocampus. These findings suggest that evaluating gwBZ and gwBTV in AD brain could be a useful tool for monitoring AD progression and diagnosis.

Effects of Kami Guibi-tang in patients with mild cognitive impairment: study protocol for a phase III, randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is often considered a precursor to Alzheimer's disease (AD) and represents a key therapeutic target for early intervention of AD. However, no treatments have been approved for MCI at present. Our previous pilot study has shown that Kami Guibi-tang (KGT), a traditional herbal prescription widely used in Korean medicine for treating amnesia, might be beneficial for improving general cognitive function of aMCI patients. We will conduct a larger-scale clinical trial to validate the findings of our pilot study and further examine the efficacy and safety of KGT in aMCI. METHODS: This trial is designed as a randomized, double-blind, placebo-controlled clinical trial. A total of 84 aMCI patients will be recruited and randomized into the treatment and control groups. Participants will be administered either KGT or placebo granules for 24 weeks, with a follow-up period of 12 weeks after the last treatment. Primary outcomes will include changes in cognitive performance assessed using a neuropsychological test battery, called the Seoul Neuropsychological Screening Battery, between the baseline, post-intervention visit, and follow-up visit (24th and 36th week, respectively). Secondary outcomes will involve the rate of progression to AD, changes in neuroimaging signals assessed using structural magnetic resonance imaging (MRI), resting-state functional MRI (rs-fMRI), and task-based fMRI, and changes in blood biomarkers measured by the ratio of plasma amyloid-ß 42/40 levels (Aß42/Aß40) between the baseline and post-intervention visit (24th week). For safety assessments, blood chemistry tests and electrocardiograms (ECG) will also be performed. DISCUSSION: This study aims to provide confirmatory evidence of the effect of the Korean herbal medicine, KGT, on improving cognitive function in patients with aMCI. We will identify the possible mechanisms underlying the effects of KGT using neuroimaging signals and blood biomarkers. TRIAL REGISTRATION: Korean Clinical Trial Registry ( https://cris.nih.go.kr/cris/search/detailSearch.do/16918; Registration number: KCT0007039; Date of registration: February 24, 2022).

Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes.

AIMS: Carotid atherosclerosis (CAS) is associated with a high risk of cardiovascular diseases. We aimed to investigate whether CAS is associated with the presence of intracranial atherosclerosis (ICAS). METHODS: A total of 69 asymptomatic patients with type 2 diabetes (36 with CAS and 33 without CAS) who were free of cerebrovascular disease were enrolled in this case-control study. CAS was defined as a mean carotid intima-media thickness ≥ 1.0 mm or carotid plaque. The presence of ICAS was identified using three-dimensional high-resolution vessel wall magnetic resonance imaging. RESULTS: There was no difference between the case and control groups in baseline characteristics, such as age, the proportion of men, duration of diabetes, and other cardiometabolic risk factors. The prevalence of ICAS was significantly higher in patients with CAS than those without CAS (72.2 % vs 48.5 %, P = 0.044). CAS was significantly associated with the presence of ICAS, even after adjusting other covariates (odds ratio [OR], 3.19; 95 % confidence interval [CI] 1.09-9.33, P = 0.034). In addition, CAS was significantly associated with the presence of multiple ICAS lesions (OR, 5.57; 95 % CI 1.75-17.78, P = 0.004). CONCLUSIONS: CAS is significantly and independently associated with the presence and extent of ICAS in asymptomatic patients with type 2 diabetes.

Application of High-Frequency Conductivity Map Using MRI to Evaluate It in the Brain of Alzheimer's Disease Patients.

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.

Ultrasensitive probeless capacitive biosensor for amyloid beta (Aß1-42) detection in human plasma using interdigitated electrodes.

Progressive aggregation and protein misfolding are the initial fundamental indicators of neurodegenerative disorders such as Alzheimer's disease (AD). In this study, a highly sensitive and novel method to detect amyloid beta (Aß) biomarkers, which are a hallmark of AD, using an immunoassay platform-based interdigitated capacitive biosensor, has been explored. For several decades, aptamers have classified as a novel class of molecular recognition probes comprising single-stranded complementary DNA sequences that bind to their identified targets with high specificity and affinity by an in vitro technique called SELEX (systematic evolution of exponential and enrichment). Aptamers, often referred to as "chemical antibodies", possess several highly obvious features for clinical use. The proposed sensing bio-device was fabricated and glazed with oligomeric Aß (oAß) aptamer and anti-oAß antibody, functionalized onto a Pt/Ti-featured SiO2 substrate. Subsequently, analytical studies were conducted to confirm that the specificity, sensitivity, and selective detection of the oAß-based bioengineered surfaces facilitate a label-free approach. The bionic capacitive sensor achieved real-time detection within 5 s (faster response than ELISA) under the femto-molar range concentrations of oAß peptide in plasma using anti-oAß antibody and oAß aptamer with ultra-high affinity. Furthermore, the prepared capacitive biochip was selective against plasma-borne antigens and standby for 100 days at 4 °C. The developed biosensor is suitable for point-of-care (POC) diagnostic applications owing to its portability and scalability. Furthermore, the superior efficacy of oAß in identifying AD has huge potential for biomedical applications.

Myelin-Weighted Imaging Presents Reduced Apparent Myelin Water in Patients with Alzheimer's Disease.

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.

Association Between Plasma Amyloid-ß and Neuropsychological Performance in Patients With Cognitive Decline.

Objective: To investigate the association between plasma amyloid-ß (Aß) 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 Aß 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 Aß (Aß40, Aß42, and Aß42/40) levels were associated with neuropsychological test results. Results: The plasma levels of Aß42/40 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 Aß42/40 were negatively correlated only with verbal and visual memory performance. Conclusion: Our results demonstrated that plasma Aß analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline.

Efficacy and safety of Kami-guibi-tang for mild cognitive impairment: a pilot, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is considered an intermediate phase between normal aging and dementia. As the majority of cases of amnestic MCI (aMCI) progress to Alzheimer's disease (AD), it is considered the prodromal stage of AD, and a treatment target for prevention of further cognitive decline. However, no medications have been shown to have symptomatic or preventive benefits in MCI. Kami-guibi-tang (KGT) is a traditional herbal formula used in Korean medicine to treat amnesia, which is reported to increase acetylcholine levels via activation of choline acetyltransferase. The objective of this study was to evaluate the efficacy and safety of KGT in patients with aMCI. METHODS: This study was designed as a single-center, randomized, double-blind, placebo-controlled pilot study. Participants diagnosed with aMCI were randomized to receive either KGT or placebo granules for 24 weeks. The efficacy measure was a change in the Seoul Neuropsychological Screening Battery (SNSB) score. The safety measures included the occurrence of adverse events and abnormalities in vital signs and blood chemistry, electrocardiogram (ECG), and brain magnetic resonance imaging (MRI) findings. RESULTS: A total of 16 patients in the KGT group and 14 patients in the placebo group were investigated in the study. The mean score of Clinical Dementia Rating-Sum of Boxes (CDR-SB) significantly improved from 1.53 (0.64) points to 1.13 (0.62) points in the KGT group (p = 0.010), whereas it worsened from 1.61 (0.88) points to 1.75 (0.94) points in the placebo group. There was a significant difference in the CDR-SB scores between the two groups after the intervention (p = 0.045). The total SNSB-D scores and the scores in the memory domain after the treatment were significantly higher than the baseline values in the KGT group, but not in the placebo group. The frequency of adverse events was not significantly different between the two groups, and there were no abnormalities in vital signs or blood test, ECG, and brain MRI findings after the intervention. CONCLUSIONS: KGT may provide a safe and effective treatment option for patients with aMCI. Further studies with a larger sample size are needed to validate the findings. TRIAL REGISTRATION: Korean Clinical Trial Registry, ID: KCT0002407; Registered on March 30, 2017, http://cris.nih.go.kr/.

Treatment evaluation of Kami Guibi-tang on participants with amnestic mild cognitive impairment using magnetic resonance imaging on brain metabolites, gamma-aminobutyric acid, and cerebral blood flow.

PURPOSE: To evaluate the effectiveness of Kami Guibi-tang (KGT) in the treatment of mild cognitive impairment (MCI) using magnetic resonance imaging (MRI) on brain metabolites, neurotransmitter, and cerebral blood flow (CBF). METHODS: We randomly allocated a total of 30 MCI patients to a KGT (N = 16) or a placebo (N = 14) group and performed MRI scans before and after 24 weeks of treatment. The participants underwent brain magnetic resonance spectroscopy and MRI scans to obtain brain metabolites using Point-RESolved Spectroscopy (PRESS) single-voxel spectroscopy, gamma-aminobutyric acid (GABA) neurotransmitter using Mescher-Garwood PRESS, and CBF using pseudocontinuous arterial spin labeling sequences using a 3.0 Tesla MRI system. We analyzed metabolite and neurotransmitter levels and CBF using repeated-measure analysis of variance to evaluate between-subject group effect, within-subject treatment condition effect, and interaction of group by condition (group x condition). RESULTS: The GABA+/creatine (Cr) ratio values were not significantly different between the before and after treatment conditions. The glutamate complex/Cr ratio difference before and after treatment was lower in the KGT group than in the placebo group, but was not statistically significant (p = 0.077). The result of region of interest-based CBF measurement showed that CBF values were significantly lower after treatment at Cluster 2 for the KGT group (p = 0.003) and the placebo group (p = 0.011), at hippocampus for the KGT group (p = 0.004) and the placebo group (p = 0.008), and at the fusiform gyrus for the KGT group (p = 0.002). Furthermore, the absolute CBF difference before and after treatment in the fusiform gyrus was significantly lower in the KGT group than in the placebo group (p = 0.024). CONCLUSIONS: Although a KGT treatment of 24 weeks showed some significant impact on the level of CBF, the Korean version of the mini-mental state examination score was not significantly different between before and after treatment conditions, indicating that there was no memory function improvement after treatment in amnestic MCI patients. Therefore, further studies should be performed with a relatively larger population and extending the duration of the KGT treatment.