Quantitative Thermal Stimulation Using Therapeutic Ultrasound to Improve Cerebral Blood Flow and Reduce Vascular Stiffness.

It is important to improve cerebrovascular health before the occurrence of cerebrovascular disease, as it has various aftereffects and a high recurrence rate, even with appropriate treatment. Various medical recommendations for preventing cerebrovascular diseases have been introduced, including smoking cessation, exercise, and diet. However, the effectiveness of these methods varies greatly from person to person, and their effects cannot be confirmed unless they are practiced over a long period. Therefore, there is a growing need to develop more quantitative methods that are applicable to the public to promote cerebrovascular health. Thus, in this study, we aimed to develop noninvasive and quantitative thermal stimulation techniques using ultrasound to improve cerebrovascular health and prevent cerebrovascular diseases. This study included 27 healthy adults in their 20s (14 males, 13 females). Thermal stimulation using therapeutic ultrasound at a frequency of 3 MHz was applied to the right sternocleidomastoid muscle in the supine posture for 2 min at four intensities (2.4, 5.1, 7.2, and 10.2 W/cm2). Diagnostic ultrasound was used to measure the peak systolic velocity (PSV), heart rate (HR), and pulse wave velocity (PWV) in the right common carotid artery (CCA), and the physiological changes were compared between intervention intensities. Compared to pre-intervention (preI), the PSV showed a significant increase during intervention (durI) at intensities of 7.2 W/cm2 and 10.2 W/cm2 (p = 0.010 and p = 0.021, respectively). Additionally, PWV showed a significant decrease for post-intervention (postI) at 7.2 W/cm2 and 10.2 W/cm2 (p = 0.036 and p = 0.035, respectively). However, the HR showed no significant differences at any of the intensities. The results demonstrate that an intervention at 3 MHz with an intensity of 7.2 W/cm2 or more can substantially increase cerebral blood flow and reduce arterial stiffness. Therefore, the use of therapeutic ultrasound of appropriate intensity is expected to improve the cerebral blood flow and reduce vascular stiffness to maintain cerebral blood flow at a certain level, which is closely related to the prevention and treatment of cerebrovascular diseases, thereby improving cerebrovascular health.

MRI-negative myelitis associated with MOG-IgG antibody: A case report and literature reviews.

According to few case reports, myelin oligodendrocyte glycoprotein-associated disease (MOGAD) could present as myelitis subtype with normal spine MRI, though it is rare. Herein, we report a case of clinically myelitis but MRI was normal, with strongly positive anti-MOG-IgG antibody in the sera. The patient showed a rapid improvement following a high dose methylprednisolone treatment.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial.

BACKGROUND: Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. METHODS: This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks. RESULTS: Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P=0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported. CONCLUSIONS: The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.

MRI-Compatible Microcirculation System Using Ultrasonic Pumps for Microvascular Imaging on 3T MRI.

The diagnosis of small vessel disease is attracting interest; however, it remains difficult to visualize the microvasculature using 3 Tesla (T) magnetic resonance imaging (MRI). Therefore, this study aimed to visualize the microvascular structure and measure a slow flow on 3T MRI. We developed a microcirculation system using piezoelectric pumps connected to small tubes (0.4, 0.5, 0.8, and 1.0 mm) and evaluated various MR sequences and imaging parameters to identify the most appropriate acquisition parameters. We found that the system could image small structures with a diameter of 0.5 mm or more when using a 1 m-long tube (maximal signal intensity of 241 in 1 mm, 199 in 0.8 mm, and 133 in 0.5 mm). We also found that the highest signal-to-noise ratio (SNR) appeared on 2-dimensional time-of-flight low-resolution imaging and that the flow velocity (10.03 cm/s) was similar to the actual velocity (11.01 cm/s in a flowmeter) when velocity encoding of 30 cm/s was used in a 0.8 mm-diameter tube. In conclusion, this study demonstrates that a microcirculation system can be used to image small vessels. Therefore, our results could serve as a basis for research on vessels' anatomical structure and pathophysiological function in small vessel disease.

miR-200c suppression increases tau hyperphosphorylation by targeting 14-3-3γ in early stage of 5xFAD mouse model of Alzheimer's disease.

Background and Purpose: Recently, several abnormally regulated microRNAs (miRNAs) have been identified in patients with Alzheimer's disease (AD). The purpose of this study was to identify abnormally expressed miRNAs and to investigate whether they affect pathological changes in AD in the 5xFAD AD mouse model. Experimental Approach: Using microarray analysis and RT-qPCR, miRNA expression in the hippocampus of a 4-month-old 5xFAD mouse model of AD was investigated. A dual-luciferase assay was performed to determine whether the altered miR-200c regulates the translation of the target mRNA, Ywhag. Whether miR-200c modulates AD pathology was determined in primary hippocampal neurons and C57BL/6J mice transfected with miR-200c inhibitor. In addition, total miRNAs were extracted from the serums of 28 healthy age-matched controls and 22 individual participants with cognitive impairment, and RT-qPCR was performed. Key results: miR-200c expression was reduced in the hippocampus of 5xFAD mice. In primary hippocampal neurons, miR-200c regulated the translation of 14-3-3γ and increased tau phosphorylation (p-tau) by increasing p-GSK-3ß (GSK-3ß phosphorylation). It was also confirmed that miR-200c inhibition in the hippocampus of C57BL/6J mice induces cognitive impairment and increases tau phosphorylation through 14-3-3γ activation. Finally, aberrant expression of miR-200c was confirmed in the blood serum of human AD patients. Conclusion and Implications: Our results strongly suggest that dysregulation of miR-200c expression contributes to the pathogenesis of AD, including cognitive impairment through hyperphosphorylated tau.

Investigation of Flow Changes in Intracranial Vascular Disease Models Constructed with MRA Images.

This study aimed to develop a magnetic resonance imaging (MRI)-compatible flow delivery system and individualized models of circle of Willis (CoW), which include 50% and 100% blockage in internal carotid artery (ICA50 and ICA100), and 100% blockage in vertebral artery (VA100). Images were obtained using 3D time-of-flight and phase-contrast magnetic resonance angiography (MRA) sequences, and changes in velocity and flow direction at CoW models were analyzed. For the ICA50 and VA100 models, the flow was similar to that of the normal model. For the ICA 50 model, it was found that 50% blockage did not affect cerebral blood flow. For the VA100 model, decreased flow in the posterior cerebral artery and a change to the flow direction in the posterior communicating artery were found. For the ICA100 model, particularly, decreased flow in the ipsilateral middle and anterior cerebral arteries and a change to the flow direction in the ipsilateral anterior cerebral artery of the CoW were found. These results demonstrated that the flow system with various CoW disease models tailored to individual characteristics could be used to predict stroke onset more quickly. For the ICA50 and VA100 models, the possibility of cerebral infarction was significantly lower. On the other hand, for the ICA100 model, there was a high possibility of decreased flow, which could lead to cerebral infarction.

Severity Evaluation of Regional Cerebrovascular Reactivity in Acute Stroke Patients Using SPECT.

BACKGROUND: Cerebrovascular Reactivity (CVR), as measured using perfusion Single Photon Emission Computed Tomography (SPECT), is an important indicator for the treatment and prognosis of cerebrovascular disease, but there are a few studies on acute stroke or small vascular disease using SPECT. OBJECTIVE: This study evaluated the regional severity with quantitatively determined CVR in patients with acute stroke. METHODS: Fifty-eight patients who took brain SPECT images were selected to localize quantitative CVR values. The severity of the disease (Grade 1 to 4) was determined through image-based clinical assessment in the absence and presence of a CVR map, and their results were compared. RESULTS: In 1st diagnosis without the map, the mean CVR values of Grades 2 and 3 were -6.07 % and -9.12 %, respectively (P=0.034), while they were -4.78 % and -12.34 % in 2nd diagnosis with the map, respectively (P<0.001), suggesting that the CVR difference with the map was much more pronounced than without the map. Furthermore, in the ROC analysis, the diagnostic sensitivity between Grades 2 and 3 in the 2nd diagnosis (AUC=0.899, P<0.001) was substantially greater than the 1st diagnosis (AUC=0.646, P=0.048). CONCLUSION: This study demonstrated that the quantitative CVR maps could reinforce the clinical evaluation of cerebral severity by showing that they can provide statistically significant results between severity and CVR. Furthermore, this study was the first to evaluate the effectiveness of quantitative CVR by examining the difference in the presence or absence of CVR in patients with acute stroke.

Resting-state Functional Connectivity During Controlled Respiratory Cycles Using Functional Magnetic Resonance Imaging.

Introduction: This study aimed to assess the effect of controlled mouth breathing during the resting state using functional magnetic resonance imaging (fMRI). Methods: Eleven subjects participated in this experiment in which the controlled "Nose" and "Mouth" breathings of 6 s respiratory cycle were performed with a visual cue at 3T MRI. Voxel-wise seed-to-voxel maps and whole-brain region of interest (ROI)-to-ROI connectome maps were analyzed in both "Nose>Mouth" and "Mouth>Nose" contrasts. Results: As a result, there were more connection pairs in the "Mouth" breathing condition, i.e., 14 seeds and 14 connecting pairs in the "Mouth>Nose" contrast, compared to 7 seeds and 4 connecting pairs in the "Nose>Mouth" contrast (false discovery rate [FDR] of P<0.05). Conclusion: The present study demonstrated that mouth breathing with controlled respiratory cycles could significantly induce alterations in functional connectivity in the resting-state network, suggesting that it can differently affect resting brain function; in particular, the brain can hardly rest during mouth breathing, as opposed to conventional nasal breathing.

Novel Technique to Measure Pulse Wave Velocity in Brain Vessels Using a Fast Simultaneous Multi-Slice Excitation Magnetic Resonance Sequence.

In this study, we proposed a novel pulse wave velocity (PWV) technique to determine cerebrovascular stiffness using a 3-tesla magnetic resonance imaging (MRI) to overcome the various shortcomings of existing PWV techniques for cerebral-artery PWV, such as long scan times and complicated procedures. The technique was developed by combining a simultaneous multi-slice (SMS) excitation pulse sequence with keyhole acquisition and reconstruction (SMS-K). The SMS-K technique for cerebral-artery PWV was evaluated using phantom and human experiments. In the results, common and internal carotid arteries (CCA and ICA) were acquired simultaneously in an image with a high temporal resolution-of 48 ms for one measurement. Vascular signals at 500 time points acquired within 30 s could generate pulse waveforms of CCA and ICA with 26 heartbeats, allowing for the detection of PWV changes over time. The results demonstrated that the SMS-K technique could provide more PWV information with a simple procedure within a short period of time. The procedural convenience and advantages of PWV measurements will make it more appropriate for clinical applications.

Investigation of Functional Connectivity Differences between Voluntary Respirations via Mouth and Nose Using Resting State fMRI.

The problems of mouth breathing have been well-studied, but the neural correlates of functional connectivity (FC) still remain unclear. We examined the difference in FC between the two types of breathing. For our study, 21 healthy subjects performed voluntary mouth and nasal breathing conditions during a resting state functional magnetic resonance imaging (fMRI). The region of interest (ROI) analysis of FC in fMRI was conducted using a MATLAB-based imaging software. The resulting analysis showed that mouth breathing had widespread connections and more left lateralization. Left inferior temporal gyrus had the most left lateralized connections in mouth breathing condition. Furthermore, the central opercular cortex FC showed a significant relationship with mouth breathing. For nasal breathing, the sensorimotor area had symmetry FC pattern. These findings suggest that various FCs difference appeared between two breathing conditions. The impacts of these differences need to be more investigated to find out potential link with cognitive decline in mouth breathing syndrome.

Longitudinal profiling of oligomeric Aß in human nasal discharge reflecting cognitive decline in probable Alzheimer's disease.

Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer's disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-ß (Aß), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aß oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aß by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aß oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aß*56 and 15-mer AßO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aß*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aß proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression.

Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression.

Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer's disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid ß (Aß1-42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression.

[¹8F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹8F]THK5351 in MCI subgroups. METHODS: This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [¹8F]THK5351 PET, and detailed neuropsychological tests. [¹8F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [¹8F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [¹8F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. RESULTS: [¹8F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [¹8F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [¹8F]THK5351 retention. CONCLUSIONS: [¹8F]THK5351 PET might be useful for identifying distinct topographic patterns of [¹8F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.

EEG signals during mouth breathing in a working memory task.

Background: Continuous mouth breathing results not only morphological deformations but also poor learning outcomes. However, there were few studies that observed correlations between mouth breathing and cognition. This study aimed at investigating the changes in brain activity during mouth breathing while the participant simultaneously performed a cognitive task using electroencephalography (EEG).Methods: Twenty subjects participated in this study, and EEG electrodes (32 channels, 250-Hz sampling rate) were placed on their scalp. Brain waves during a resting state and n-back tasks (0-back and 2-back) and physiological parameters such as SpO2, ETCO2, and the airway respiratory rate were measured. The pre-processed EEG signals were analyzed based on their frequencies as delta waves (0.5 ∼ 4 Hz), theta waves (4 ∼ 8 Hz), alpha waves (8 ∼ 13 Hz), beta waves (13 ∼ 30 Hz) and gamma waves (30 ∼ 50 Hz) using fast Fourier transform (FFT).Results: When compared with nose breathing, theta and alpha powers were lower during mouth breathing at rest and alpha wave presented low power at 0-back and 2-back tasks. Furthermore, beta and gamma waves exhibited low powers at 2-back task. However, the behavioral results (accuracy and response time) have no significant difference between two breathing methods (mouth and nose). Mouth breathing showed different brain activity patterns, compared to nose breathing, and these changes are related to cognitive regions.Conclusion: The reason for this change seems to relate to the decreased oxygen saturation during mouth breathing, suggesting that when cognitive abilities are required, mouth breathing can act as one of the variables that cause different outcomes in brain activities.

Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis.

Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [18F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups. Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months. Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%). Conclusion: Using cluster analyses with [18F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia.

Comparison of the Effect of Fimasartan versus Valsartan on Blood Pressure Variability in Acute Ischemic Stroke: A Double-Blind Randomized Trial.

Higher blood pressure variability (BPV) is associated with poor functional outcome and mortality in acute stroke. This randomized controlled trial was conducted to compare the effect on BPV between fimasartan and valsartan (Boryung Pharmaceutical Co., Ltd., Seoul, Republic of Korea) in patients with acute ischemic stroke. Eighty patients were randomly assigned to receive either valsartan or fimasartan after 7 days of acute ischemic stroke onset, for duration of 8 weeks. Of them, 62 patients completed the study [valsartan (n=31), fimasartan (n=31)]. We measured BP for 24 hours using ambulatory BP monitoring device before and after 8 weeks of starting BP medication. We calculated several indexes such as standard deviation (SD), weighted 24-hour BP with SD (wSD), coefficient of variation (CV), and average real variability (ARV) to assess BPV and to compare indexes of BPV between 2 drugs. SD values of systolic BP in daytime, nighttime, and 24 h period (15.55±4.02 versus 20.55±8.77, P=0.006; 11.98±5.52 versus 16.47±6.94, P=0.007; 17.22±5.30 versus 21.45±8.51, P=0.024), wSD of systolic BP (8.27±3.01 versus 10.77±4.18, P=0.010), and ARV of systolic BP (15.85±6.17 versus 19.68±7.83, P=0.040) of patients receiving fimasartan after 8 weeks were significantly lower than patients receiving valsartan. In paired t-test, SD values of daytime, nighttime, and 24 h period of systolic BP of patients receiving fimasartan were significantly decreased after 8 weeks (15.55±4.02 versus 18.70±7.04, P=0.038; 11.98±5.52 versus 17.19±7.35, P=0.006; 17.22±5.30 versus 20.59±5.91, P=0.015). Our study showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan. Trials registry number is KCT0003254.

Relationships between [¹8F]-THK5351 Retention and Language Functions in Primary Progressive Aphasia.

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹8F]-THK5351 retention across all three subtypes and determine the topography of [¹8F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹8F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹8F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹8F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹8F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹8F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹8F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹8F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹8F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹8F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Topographical Heterogeneity of Alzheimer's Disease Based on MR Imaging, Tau PET, and Amyloid PET.

Alzheimer's disease (AD) patients are known to have heterogeneous clinical presentation and pathologic patterns. We hypothesize that AD dementia can be categorized into subtypes based on multimodal imaging biomarkers such as magnetic resonance imaging (MRI), tau positron emission tomography (PET), and amyloid PET. We collected 3T MRI, 18F-THK5351 PET, and 18F-flutemetamol (FLUTE) PET data from 83 patients with AD dementia [Clinical Dementia Rating (CDR) ≤1] and 60 normal controls (NC), and applied surface-based analyses to measure cortical thickness, THK5351 standardized uptake value ratio (SUVR) and FLUTE SUVR for each participant. For the patient group, we performed an agglomerative hierarchical clustering analysis using the three multimodal imaging features on the vertices (n = 3 × 79,950). The identified AD subtypes were compared to NC using general linear models adjusting for age, sex, and years of education. We mapped the effect size within significant cortical regions reaching a corrected p-vertex <0.05 (random field theory). Our surface-based multimodal framework has revealed three distinct subtypes among AD patients: medial temporal-dominant subtype (MT, n = 44), parietal-dominant subtype (P, n = 19), and diffuse atrophy subtype (D, n = 20). The topography of cortical atrophy and THK5351 retention differentiates between the three subtypes. In the case of FLUTE, three subtypes did not show distinct topographical differences, although cortical composite retention was significantly higher in the P type than in the MT type. These three subtypes also differed in demographic and clinical features. In conclusion, AD patients may be clustered into three subtypes with distinct topographical features of cortical atrophy and tau deposition, although amyloid deposition may not differ across the subtypes in terms of topography.

Medication Adherence of Statin Users after Acute Ischemic Stroke.

Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients' awareness of hyperlipidemia (OR 1.62; 95% CI 1.07-2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19-2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06-2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40-0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88-0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.