The amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder.

The purpose of this study was to demonstrate the potential alterations in structural network properties related to physical activity (PA) in healthy elderly. We recruited 76 elderly individuals with normal cognition from Samsung Medical Center in Seoul, Korea. All participants underwent the Cambridge Neuropsychological Test Automated Battery and 3.0T brain magnetic resonance imaging (MRI). Participants were subdivided into quartiles according to the International Physical Activity Questionnaire scores, which represents the amount of PA. Through graph theory based analyses, we compared global and local network topologies according to PA quartile. The higher PA group demonstrated better performance in speed processing compared to the lower PA group. Regional nodal strength also significantly increased in the higher PA group, which involved the bilateral middle frontal, bilateral inferior parietal, right medial orbitofrontal, right superior, and middle temporal gyri. These results were further replicated when the highest and the lowest quartile groups were compared in terms of regional nodal strengths and local efficiency. Our findings that the regional nodal strengths associated with the attentional network were increased in the higher PA group suggest the preventive effects of PA on age-related cognitive decline, especially in attention.

The protective effect of education has been well established in Alzheimer's disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with pure subcortical vascular dementia (SVaD).

Background: In neuromyelitis optica spectrum disorder (NMOSD), brain involvement is common and cognitive dysfunction is frequently found. The study investigated alterations of white matter (WM) connectivity using graph theory and correlations with cognitive dysfunction in patients with NMOSD. Methods: We prospectively enrolled patients with NMOSD (N = 14) and age- and sex-matched healthy controls (N = 21). Structural connections between any pair of the 90 cortical and subcortical regions were established using diffusion tensor imaging and graph theory. Network-based statistics was employed to assess differences in WM connectivity between the NMOSD and healthy control groups. We further investigated the relationship between the topological network characteristics and cognitive test performances. Results: WM network analysis showed decreased total strength of brain networks and two disrupted sub-networks in patients with NMOSD. The first featured six hub nodes in the rectus, hippocampus, calcarine, cuneus, and precuneus with the left-sided predominance. The second had six hub nodes in the orbitomiddle frontal, post-central, superior parietal, superior, and middle temporal, and caudate with the right-sided predominance. Compared to healthy controls, NMOSD patients showed poor performance on tests for attention/working memory and processing speed, visuospatial processing, and executive function, which were associated with significant decreases in nodal clustering coefficient, local efficiency, and regional efficiency in the disrupted sub-networks (all p < 0.05). Conclusions: The data show the overall WM disruption and the relationship between poor cognitive function and sub-network alterations identified by the network analysis in NMOSD patients. We suggest that cognitive dysfunction is related to dysconnectivity of WM network including default mode network in NMOSD.

To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method.

Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) may induce functional modulation of motor performance and sensory perception. To address the underlying neurophysiological modulation following 10 Hz rTMS applied over M1, we examined cortical activation using 3T functional magnetic resonance imaging (fMRI), as well as the associated motor and sensory behavioral changes. The motor performance measure involved a sequential finger motor task that was also used as an activation task during fMRI. For sensory assessment, current perception threshold was measured before and after rTMS outside the MR scanner, and noxious mechanical stimulation was used as an activation task during fMRI. We found that significant activation in the bilateral basal ganglia, left superior frontal gyrus, bilateral pre-SMA, right medial temporal lobe, right inferior parietal lobe, and right cerebellar hemisphere correlated with enhanced motor performance in subjects that received real rTMS compared with sham-stimulated controls. Conversely, significant deactivation in the right superior and middle frontal gyri, bilateral postcentral and bilateral cingulate gyri, left SMA, right insula, right basal ganglia, and right cerebellar hemisphere were associated with an increase in the sensory threshold. Our findings reveal that rTMS induced rapid changes in the sensorimotor networks associated with sensory perception and motor performance and demonstrate the complexity of such intervention.

Oligomeric amyloid-ß is a major toxic species associated with Alzheimer's disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain.

Among mild cognitive impairment (MCI) patients, those with memory impairment (amnestic MCI, aMCI) are at a high risk of dementia. However, the precise cognitive domain, beside memory, that predicts dementia conversion is unclear. Therefore, we investigated the cognitive domain that predicts dementia conversion in a longitudinal aMCI cohort. We collected data of 482 aMCI patients who underwent neuropsychological tests and magnetic resonance imaging at baseline and were followed for at least 1 year. The patients were categorized according to number (1-4) and type of impaired cognitive domains (memory, language, visuospatial, and frontal-executive function). We evaluated dementia conversion risk in each group when compared to single-domain aMCI after controlling for age, education, diabetes and dyslipidemia. Baseline cortical thickness of each group was compared to that of 410 cognitively normal controls (NCs) after controlling for age, intracranial volume, diabetes and dyslipidemia. Compared to single-domain aMCI, aMCI patients with frontal-executive dysfunction at baseline had a higher risk of dementia conversion than aMCI patients with visuospatial or language dysfunction. Compared to NCs, aMCI patients with frontal-executive dysfunction had overall cortical thinning including frontal areas. Our findings suggest that aMCI patients with frontal-executive dysfunction have poor prognosis and,thus, should be considered for intervention therapy with a higher priority among aMCI patients.

Cognitive dysfunction has long been recognized as a frequently observed symptom in individuals with repetitive mild traumatic brain injury (rmTBI) such as professional boxers. The exact neurobiological mechanisms underlying this cognitive deficit have not yet been identified, but it is agreed upon that the prefrontal cortex (PFC) is one of the most commonly affected brain regions in professional boxers. Noting the pivotal role of the two major brain metabolites in human cognitive functions, γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx), we hypothesized that alterations in levels of GABA and Glx in the PFC would be prominent and may correlate with cognitive deficits in professional boxers. Twenty male professional boxers (Boxers) and 14 age-matched healthy males who had never experienced any TBI (CON) were recruited. Using a 3T magnetic resonance imaging (MRI) scanner, single-voxel proton magnetic resonance spectroscopy with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence was performed to evaluate the levels of GABA and Glx in the PFC. Cognitive function was assessed using the memory and attention domains from the Cambridge Neuropsychological Test Automated Battery. The Boxers showed lower GABA level in the PFC compared to the CON, while also showing lower performance in the attention and memory domains. There were no significant between-group differences in Glx levels. Furthermore, the GABA level correlated with memory performance in the Boxers, but not in attention performance. The current findings may suggest that alterations in GABA levels in the PFC may be a potential neurochemical correlate underlying memory dysfunction related to rmTBI.

Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans.

Triple intrinsic brain networks including the salience network (SN), default mode network (DMN), and central executive network (CEN), are known to be important in human cognition. Therefore, investigating those intrinsic brain networks in transient global amnesia (TGA) may offer novel insight useful for the pathophysiology of TGA. Fifty TGA patients underwent the resting state functional magnetic resonance imaging (rsfMRI) within 24 h, at 72 h, and 3 months after TGA onset. Twenty-five age, gender matched controls also underwent rsfMRI. Within 24 h of TGA onset, TGA patients showed greater functional connectivity in the SN and lower functional connectivity in the DMN, while relatively preserved functional connectivity was observed in the CEN. Interestingly, TGA patients continued to show decreased connectivity in the DMN, while no alterations were shown in the SN 72 h after illness onset. Three months after TGA onset, alterations of functional connectivity in the SN or the DMN were normalized. Our findings suggest that TGA is associated with transient greater functional connectivity in the SN and lower connectivity in the DMN.

Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ- aMCI patients.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.

The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

The aim of this study was to develop a coenzyme Q10 (CoQ10) microemulsion system with improved solubility, penetration, and wound healing efficacy. Based on the pseudo-ternary diagram, microemulsions containing isopropyl myristate (IPM), Cremophor EL®, and Transcutol® HP were selected and confirmed to be nanosized (<20 nm) and thermodynamically stable based on the dilution and thermodynamic stability tests. The CoQ10-loaded microemulsion with a surfactant/co-surfactant (S/CoS) ratio of 2:1 (w/w %) demonstrated a higher permeation efficacy compared to microemulsions with S/CoS ratio of 3:1 or 4:1 (w/w %). Additionally, the CoQ10-loaded microemulsion with an S/CoS ratio of 2:1 demonstrated a relatively rapid wound healing effect in keratinocytes and fibroblasts. Overall, these data suggest that a microemulsion based on IPM, Cremophor EL®, and Transcutol® HP could be an effective vehicle for the topical administration of CoQ10 and could be utilized for the application of other therapeutic agents that have difficulty in penetrating the skin.

Biodegradable nanoparticles (NPs) are preferred as drug carriers because of their effectiveness in encapsulating drugs, ability to control drug release, and low cytotoxicity. Although poly(lactide co-glycolide) (PLGA)-based NPs have been used for controlled release strategies, they have some disadvantages. This study describes an approach using biodegradable polyhydroxyalkanoate (PHA) to overcome these challenges. By varying the amount of PHA, NPs were successfully fabricated by a solvent evaporation method. The size range of the NPS ranged from 137.60 to 186.93 nm, and showed zero-order release kinetics of paclitaxel (PTX) for 7 h, and more sustained release profiles compared with NPs composed of PLGA alone. Increasing the amount of PHA improved the PTX loading efficiency of NPs. Overall, these findings suggest that PHA can be used for designing polymeric nanocarriers, which offer a potential strategy for the development of improved drug delivery systems for sustained and controlled release.

We investigated the effect of education on the edge efficiency in resting state functional networks (RSFNs) in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). We collected the data of 57 early aMCI, 141 late aMCI, 173 mild ADD, and 39 moderate-to-severe ADD patients. We used years of education as a proxy for cognitive reserve. We measured edge efficiency for each edge in RSFNs, and performed simple slope analyses to discover their associations with education level among the four groups. In the late aMCI, a sub-network that had hub nodes in the right middle frontal gyrus and the right posterior cingulate gyrus, showed a positive association between RSFN edge efficiency and education (threshold = 2.5, p = 0.0478). There was no negative effect of education on the RSFN edge efficiency. In the early aMCI, mild ADD, and moderate-to-severe ADD, there were no sub-networks showing positive or negative correlation between education and RSFN edge efficiency. There was a positive effect of higher education on RSFN edge efficiency in the late aMCI, but not in the early aMCI or ADD. This indicates that in late aMCI, those who have higher education level have greater ability to resist collapsed functional network.

The present study reports two novel genome-wide significant loci for late-onset Alzheimer's disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer's disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer' and Related Dementias (GARD) cohort study. The study was replicated in a Japanese cohort of 1,956 subjects that suggested two novel susceptible SNPs in two genes: LRIG1 and CACNA1A. This study demonstrates that the discovery of AD-associated variants is feasible in non-European ethnic groups using samples comprising fewer subjects from the more homogeneous genetic background.

Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data.

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly.