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Background: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non‐memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. Methods: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning‐based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non‐cognitive scales, and resting‐state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within‐ and between‐group comparisons, group × time interactions, and seed‐to‐voxel analyses in memory‐involving brain networks were performed. Results: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal‐frontal and fusiform‐occipital network. No other cognitive and non‐cognitive symptoms differed between groups after adjusting for covariates. Conclusion: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis. [ABSTRACT FROM AUTHOR]

Light scattering holds immense significance in various applications, including LED lighting, display enhancement, and solar cell optimization, emphasizing the critical role of understanding scattering mechanisms, especially light–matter interactions, achieving effective optical diffusion. Consequently, the influence of stimuli on material properties, including refractive indices and thermal expansion behavior, has emerged as a pivotal consideration, leading to the development of stimuli‐responsive light scattering modifier. Here, a temperature‐sensitive light scattering modifier composed of poly(methyl methacrylate‐co‐styrene) and poly(ethylene‐co‐vinyl acetate) is presented as scattering particles and matrix, respectively, using a melt‐blending process. Optical properties are evaluated across controlled temperatures 0–70 °C. These findings demonstrate an increasing trend in diffuse transmission and haze as temperatures increased across all light scattering modifiers. Significantly, the optimized light scattering modifier, integrating a dual particle system, showcased uniform reduction gaps in parallel transmission and adjustable haze characteristics across the visible spectrum under temperature control. This optical modifier achieved a total transmission of 92% and adjustable haze levels ranging from 35% to 90% under temperature control. Furthermore, this fabrication of three‐layer films incorporating the light scattering modifier exhibited identical characteristics to the developed light scattering modifier, emphasizing their potential for seamless integration across diverse technological domains. [ABSTRACT FROM AUTHOR]

Fine‐tuning the sensing properties of carbon dioxide (CO2) colorimetric sensors is a challenging task. In this study, a short synthetic route is developed for CO2‐responsive nanoparticles with diverse sensitivity and detection range across a wide range of CO2 concentrations. This involves the addition of oily liquids as inter‐chain spacers, which changes the diffusivity of CO2 gas into the sensing matrices without other chemical modifications. R values and the limit of detection (LOD) are estimated from Euclidean distance (ED) curves, indicating a ten‐fold difference in sensitivity. Optical and physical analyses revealed that these results arise from intercalating inter‐chain spacers between polymeric chains and modifying the gas diffusivity. Furthermore, the sensitivity and detection range can be easily tuned by mixing two CO2‐responsive nanoparticles having different inter‐chain spacers, allowing the fabrication of the sensors with subtle differences in sensitivity and detection range. Based on these results, a CO2 level meter with a horizontal linear gauge that allows visible identification of the level of CO2 over the entire range of CO2 concentrations (from 0% to 100%) is developed. Consequently, the findings will be helpful in achieving a better understanding of gas information and finding an effective way to control the characteristics of colorimetric sensors. [ABSTRACT FROM AUTHOR]

Und: Alzheimer's disease (AD) is characterized by cognitive dysfunction likely secondary to progressive neurodegeneration in the brain. However, to what extent regional cortical thickness (CT) changes are related to cognitive decline in the Asian population remains unclear. Method: We measured CT using Freesurfer v6 from T1‐weighted magnetic resonance imaging (MRI) data in 603 Korean participants, including 71 young and 288 old cognitively unimpaired (CU young and CU old), 149 with mild cognitive impairment (MCI), and 92 AD from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE). Cognitive function of each participant was quantified by the MMSE. MRI and cognitive data were acquired at baseline (n = 603) and a 2‐year follow‐up visit (n = 380). Linear mixed‐effect models were used to estimate diagnosis group, time, and group‐by‐time interaction effects on CT measurements, with age, sex, and education as covariates. Pearson's correlations between CT measurements and MMSE total score were computed, corrected for multiple comparisons by false discovery rate (FDR). Result: At baseline, CU old participants had lower CT values than CU young participants in the inferior parietal cortex and frontal and parietal regions. In comparison with CU old participants, MCI and AD showed widespread lower CT values, more pronounced in the medial temporal lobe (i.e., the entorhinal cortex and parahippocampal gyrus), inferior temporal cortex, medial prefrontal cortex, and medial parietal cortex (i.e., the posterior cingulate cortex and precuneus), with AD lower than MCI in these regions. These regions also showed the most longitudinal atrophy in both AD and MCI over 2 years. AD patients showed faster and more widespread atrophy patterns than MCI and CU old participants. We identified significant (PFDR<0.05) positive linear correlations between cognitive decline and regional CT measurements, particularly in regions showing significant cortical thinning across time. Conclusion: In this study, we replicated the typical cross‐sectional and longitudinal brain atrophy patterns, and relationships with cognitive decline in an Asian cohort. Our findings support the generalizability of atrophy patterns in MCI and AD, suggesting common neurobiological mechanisms underlying AD symptoms across different ethnoracial populations. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) measures water diffusion within brain tissue and can provide information regarding white matter, myelin, and axonal degeneration. We analyzed the cingulum bundle of the hippocampus (CBH), chosen for relevance to Alzheimer's Disease (AD) and memory (Wen et al, 2019; Dalboni da Rocha et al, 2020), using fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AxD), and mean diffusivity (MD), as well as their relationship to cognition, measured by DTI data from the initial phase of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). Methods: Participants from KBASE included cognitively normal older adults (CN, n = 276), mild cognitive impairment (MCI, n = 142), and AD dementia (AD, n = 87) studied with baseline neuroimaging and cognitive testing at Seoul National University and processed at Indiana University School of Medicine. Affine and non‐linear transformations were used to align individual FA maps to the FMRIB58FA template (FSL). Voxel values were extracted from unilateral CBH regions (determined using JHU ICBM‐DTI‐81‐white‐matter‐labels atlas) and averaged. Univariate‐GLM and Bonferroni‐corrected post‐hoc T‐tests controlling for age and sex were used to analyze diagnostic group differences, with lower FA and higher RD, AxD, and MD values expected in MCI and AD groups compared to CN. Bonferroni‐adjusted partial correlations controlling for age, sex, and education were used to test the hypothesis that DTI values would be associated with worsening cognitive scores. Results: As hypothesized, bilateral CBH DTI values in AD and MCI were significantly worse than those in CN (p<0.001) (Fig 1) with moderate effect sizes (η2 = 0.111 – 0.307). Worsening DTI values were significantly associated with worsening Digit Span Backward, Trailmaking A and B, GDS, MMSE‐KC, CDR‐SB, Word List Recall, and Logical Memory scores at the Bonferroni‐adjusted p‐value of 0.003. Bilaterally, higher Digit Span Forward scores were significantly associated with AxD values and lower Total SMCQ scores were associated with RD, AxD, and MD values. Conclusion: Within the KBASE cohort, MCI and AD demonstrated significantly worse DTI, memory, and cognition consistent with the pattern of white matter microstructural damage previously reported in MCI and AD (Wen et al, 2019; LoBuono et al., 2019). [ABSTRACT FROM AUTHOR]

INTRODUCTION: Using nationwide cohort data, we aimed to elucidate whether baseline obesity altered the relationship between loss in body mass index (BMI) or waist circumference (WC) and risk of dementia. METHODS: Among 9689 participants whose BMIs and WCs were repeatedly measured over 1 year, 1:1 propensity score matching was conducted between participants with and without obesity (n = 2976 per group, mean age 70.9). For each group, we explored the association between loss in BMI, or WC, and incidence of dementia during an approximately 4‐year follow‐up period. RESULTS: BMI loss was associated with an increased risk of all‐cause dementia and Alzheimer's disease in participants without obesity; however, this association was absent in participants with obesity. WC loss was associated with decreased Alzheimer's disease risk only in participants with obesity. DISCUSSION: Only unfavorable loss (loss from non‐obese state) in BMI, not WC, can be a metabolic biomarker of prodromal dementia. [ABSTRACT FROM AUTHOR]

Background: White matter injury had been mostly considered a result of chronic ischemia caused by cerebral small vessel disease. However, recent studies reported that white matter degeneration could also be an important pathophysiological feature in Alzheimer's disease (AD). This study aimed to identify the relationship between AD biomarkers, particularly amyloid‐beta (Aβ) and tau deposition, with white matter hyperintensities (WMHs) representing cerebral white matter injury. Method: A total 456 older adults aging from 55 to 90 years including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aβ deposition, [18F] AV‐1451 PET for measuring tau deposition, and MRI scans with fluid‐attenuated inversion recovery image for measuring WMH volume. For PET scans, standard uptake value ratio (SUVR) was used for the analyses; combined regions of hemispheric white matter, inferior cerebellum and pons were used as the reference region when obtaining SUVRs. The relationships between Aβ or tau deposition and WMH volume were examined using multiple regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and baseline as well as change of WMH volume over 2 years were used as dependent variables. Result: Baseline Aβ deposition levels had significant positive association with longitudinal change of WMH volume over 2 years (β = 0.238, p = 0.009), but not with WMH volume at baseline. Baseline tau was not related with any of WMH volume at baseline and longitudinal change of WMH volume over 2 years. We also found significant interaction effect between baseline Aβ deposition level and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female (β = 0.427, p = 0.001), but not in male. Conclusion: Our findings suggest that Aβ deposition, but not tau, accelerates cerebral white matter injury, particularly in female. [ABSTRACT FROM AUTHOR]

Background: Circadian rest‐activity rhythm (RAR) alterations are common in the early stage of Alzheimer's disease (AD) disease. Given that the brainstem nuclei, the locus coeruleus (LC) and dorsal raphe nucleus (DRN) in particular, play key roles in modulating arousal and the sleep‐wake cycle, tau pathology in the brain stem nuclei, which occurs even before cortical tau progression, may relate to circadian RAR alteration in older individuals. Therefore, we aimed to test the hypothesis that in vivo tau deposition in the LC and DRN correlates with circadian RAR in non‐demented older adults. Method: A total of 63 non‐demented older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. All participants underwent [11C] PiB PET and [18F] AV1451‐PET. Circadian RAR variables were measured using actigraphy for 8 consecutive days. Tau deposition of the LC and DRN (LC‐tau and DRN‐tau, respectively) was measured in the regions of interest (ROI) masks for each participant prepared in native space using the Harvard arousal network atlas for the LC and DRN. For the purpose of comparison, tau deposition in the substantia nigra (SN‐tau) was also measured in the neuromelanin sensitive MRI‐based ROI for the SN. Result: Increased LC‐tau and DRN‐tau were significantly correlated with delayed acrophase (β = 0.303, p = 0.024 for LC‐tau and β = 0.398, p = 0.003 for DRN‐tau; Table 1 & Figure 1). In contrast, SN‐tau did not related with any RAR variables. Even after controlling for global tau deposition, the significance did not changed (β = 0.321, p = 0.021 for LC‐tau and β = 0.367, p = 0.008 for DRN‐tau, Table 1). In addition, Aβ positivity showed a significant moderation effect on the relationship between LC‐tau with acrophase. Subgroup analyses showed that increased LC‐tau significantly related with delayed acrophase in Aβ‐positivegroup (β = 0.427, p = 0.004), but did not in Aβ‐negative group (β = 0.099, p = 0.615)(Figure 2) Conclusion: Our findings support the possibility that the tau pathology in the LC and DRN underlie circadian RAR alteration, more specifically delayed phase, in non‐demented older adults. In addition, such relationship appears to be more prominent in individuals with brain Aβ pathology. [ABSTRACT FROM AUTHOR]

The ongoing COVID‐19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2‐anilinoquinazolin‐4(3H)‐one derivatives, and demonstrated inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and MERS‐CoV in vitro. We then conducted in vivo studies using modified compounds that are suitable for oral administration. These compounds demonstrated no toxicity in rats and inhibited viral entry. Here, we investigated the in vivo efficacy of these drug candidates against SARS‐CoV‐2. Three candidate drugs, 7‐chloro‐2‐((3,5‐dichlorophenyl)amino)quinazolin‐4(3H)‐one (1), N‐(7‐chloro‐4‐oxo‐3,4‐dihydroquinazolin‐2‐yl)‐N‐(3,5‐dichlorophenyl)acetamide (2), and N‐(7‐chloro‐4‐oxo‐3,4‐dihydroquinazolin‐2‐yl)‐N‐(3,5‐difluorophenyl)acetamide (3) were administered orally to hACE2 transgenic mice at a dose of 100 mg/kg. All three drugs improved survival rate and reduced the viral load in the lungs. These results show that the derivatives possess in vivo antiviral efficacy similar to that of molnupiravir, which is currently being used to treat COVID‐19. Overall, our data suggest that 2‐anilinoquinazolin‐4(3H)‐one derivatives are promising as potential oral antiviral drug candidates against SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Aim: The neurobiological substrates underlying the relationship of circadian rest‐activity rhythm (RAR) alteration with accelerated late‐life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia. Methods: The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [11C] Pittsburgh compound‐B positron emission tomography (PET), [18F] fluorodeoxyglucose‐PET, magnetic resonance imaging, and Mini‐Mental State Examination (MMSE) at baseline and at a 2‐year follow‐up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid‐beta retention, AD‐signature region cerebral glucose metabolism (AD‐CM), and white matter hyperintensity volume were examined. Results: Delayed acrophase at baseline was significantly associated with greater annualized decline of AD‐CM over a 2‐year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD‐CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD‐CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score. Conclusion: The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD‐signature brain regions, which underlies cognitive decline in the near future. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta‐amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum. Methods: A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [11C] Pittsburgh compound B and [18F] AV‐1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed. Results: Increased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aβ‐positive, or APOE4‐positive individuals, but not significant in the cognitively normal, Aβ‐negative, or APOE4‐negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aβ deposition. Conclusion: Brain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk. [ABSTRACT FROM AUTHOR]

The aim of this study is to provide a more accurate representation of COVID‐19's case fatality rate (CFR) by performing meta‐analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID‐19 for every country reporting COVID‐19 cases. On the basis of data, we performed random and fixed meta‐analyses for CFR of COVID‐19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed‐ and random‐model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random‐model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random‐model results showed an increase near 5.0%. In high‐income countries, pooled estimates and fixed‐model showed gradually increasing trends with a final pooled estimates and random‐model reached about 8.0% and 4.0%, respectively. In middle‐income, the pooled estimates and fixed‐model have gradually increased reaching up to 4.5%. in low‐income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID‐19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries. Highlights: Europe showed the highest COVID‐19 case fatality rate (CFR) until mid‐October 2020, and North America and South America follows.Asia showed the highest CFR since the first confirmed case of COVID‐19 emerged, however, it had shown a declining tendency since March 2020.CFRs in high‐income countries showed an explosive increase compared with those in low‐income countries, which can be interpreted as due to the under‐reporting of mortality cases from COVID‐19. [ABSTRACT FROM AUTHOR]

Above‐bandgap femtosecond optical excitation of a ferroelectric/dielectric BaTiO3/CaTiO3 superlattice leads to structural responses that are a consequence of the screening of the strong electrostatic coupling between the component layers. Time‐resolved X‐ray free‐electron laser diffraction shows that the structural response to optical excitation includes a net lattice expansion of the superlattice consistent with depolarization‐field screening driven by the photoexcited charge carriers. The depolarization‐field‐screening‐driven expansion is separate from a photoacoustic pulse launched from the bottom electrode on which the superlattice is epitaxially grown. The distribution of diffracted intensity of superlattice X‐ray reflections indicates that the depolarization‐field‐screening‐induced strain includes a photoinduced expansion in the ferroelectric BaTiO3 and a contraction in CaTiO3. The magnitude of expansion in BaTiO3 layers is larger than the contraction in CaTiO3. The difference in the magnitude of depolarization‐field‐screening‐driven strain in the BaTiO3 and CaTiO3 components can arise from the contribution of the oxygen octahedral rotation patterns at the BaTiO3/CaTiO3 interfaces to the polarization of CaTiO3. The depolarization‐field‐screening‐driven polarization reduction in the CaTiO3 layers points to a new direction for the manipulation of polarization in the component layers of a strongly coupled ferroelectric/dielectric superlattice. [ABSTRACT FROM AUTHOR]

Despite the continuing global crisis caused by coronavirus disease 2019 (COVID‐19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2‐benzylaminoquinazolin‐4(3H)‐one derivatives and demonstrated that they are effective against SARS‐CoV‐2. Among the synthesized derivatives, 7‐chloro‐2‐(((4‐chlorophenyl)(phenyl)methyl)amino)quinazolin‐4(3H)‐one (Compound 39) showed highest anti‐SARS‐CoV‐2 activity, with a half‐maximal inhibitory concentration value greater than that of remdesivir (IC50 = 4.2 μM vs. 7.6 μM, respectively), which gained urgent approval from the U.S. Food and Drug Administration. In addition, Compound 39 showed good results in various assays measuring metabolic stability, human ether a‐go‐go, Cytochromes P450 (CYPs) inhibition, and plasma protein binding (PPB), and showed better solubility and pharmacokinetics than our previous work. [ABSTRACT FROM AUTHOR]

Background: Research outcomes on intellectual development and related disabilities in North Korea are not widely known. Therefore, the current scoping review aimed to provide preliminary insight on research topics concerning intellectual disabilities in North Korea. Method: A six‐stage framework for scoping review was adopted to examine research trends. Articles were categorised based on the era of supreme leader and research topic. Results: There is a greater amount of research regarding intellectual disabilities in the recent Kim Jong‐un era compared to the period of the previous leader where research outcomes on general intelligence were the focus. Significant qualitative progress was similarly found. Conclusions: The current analysis on research outcomes provides meaningful insights to aid in understanding the atmosphere in North Korea surrounding intellectual disabilities. Follow‐up studies and open discussions are necessary for further progress. [ABSTRACT FROM AUTHOR]

Objectives: The present study examined self-reports and informant reports of cognitive function and discrepancies between the two reporting methods in healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and very mild Alzheimer disease (AD) using three questionnaires.Methods: The study included a total of 300 individuals (mean age: 74.4 ± 5.7 y), including 130 HC, 70 SCD, 51 MCI, and 49 very mild AD patients. Self-ratings and informant ratings of cognitive function were assessed using the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), AD8, and Subjective Memory Complaints Questionnaire (SMCQ). Awareness of cognitive functioning was measured on the basis of the discrepancy scores between self-reports and informant reports.Results: Group comparisons on questionnaire scores adjusting for age, education, and depressive symptoms showed that self-reports were lowest in HC than other groups, with no differences between SCD and MCI groups. Informant reports were lower in SCD than in MCI, while discrepancy scores were higher in SCD than in MCI (P < .001 for KDSQ-C and SMCQ; P = .076 for AD8). There were no differences in self-reports, informant reports, and discrepancy scores between MCI and AD groups.Conclusions: These results support the usefulness of informant-reported cognitive functioning to classify MCI among elderly with subjective cognitive complaints. In addition, discrepancies between self-reports and informant reports demonstrate that overestimation and underestimation of cognitive function may serve as a clinical indicator of SCD and MCI across the cognitive continuum, respectively. [ABSTRACT FROM AUTHOR]

Background: Most genome‐wide association studies (GWAS) of Alzheimer's disease (AD) have been conducted in populations of European ancestry. It is important to determine if known AD‐related variants from these studies are associated with AD biomarkers. Therefore, we investigated the association between known AD risk loci and in vivo brain Aβ deposition in older Korean adults. Method: Participants (n = 503) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) were analyzed. Older adults who were cognitively normal (CN), had mild cognitive impairment (MCI) or AD dementia (264 CN, 148 MCI, 91 AD) underwent comprehensive assessments including 11C‐PiB‐PET/MRI and blood sampling. Among 76 AD‐related target single nucleotide polymorphisms (SNPs) with genetic evidence compiled by the AD Sequencing Project (ADSP), 38 SNPs with minor allele frequency (MAF)>1% were extracted from TOPMed‐based imputed GWAS genotyping data in KBASE. We employed exploratory univariable logistic regression analysis with Aβ positivity as the dependent variable for each SNP. Then, SNPs with a significance level of p<0.05 were subjected to confirmatory multivariable logistic regression analysis, adjusting for age and sex, with Bonferroni correction. Result: In the first step of exploratory analyses, we discovered significant differences in Aβ positivity rates between carriers and noncarriers of minor allele of several loci, including rs16824536 in MME, rs11218343 in SORL1, rs4985556 in IL34, rs4277405 in ACE and rs3851179, located in the intergenic region between EED and PICALM. The subsequent confirmatory analysis found an association between these variants and Aβ positivity after adjusting age and sex (Table 1). Notably, the negative association of rs3851179 with Aβ positivity remained significant after correcting for multiple comparisons and after controlling for APOE4 carrier status, age, and sex (OR 0.529, 95% CI 0.345–0.813). Conclusion: We identified associations between several known AD risk loci and Aβ positivity on PET. rs3851179, demonstrated a robust association with in vivo brain Aβ positivity that was independent of APOE4 status. Our findings suggest that rs3851179 may be protective for in vivo Aβ accumulation. Additionally, the findings are needed to be replicated in other populations with different ancestries. [ABSTRACT FROM AUTHOR]

Background: Polygenic risk scores (PRS) quantify the combined effects of genetic variants to enable the prediction of an individual's risk of developing the disease. Alzheimer's disease (AD) is a complex disorder in which the relationship among PRS, neuropathological substrates, and related cognitive decline remain especially understudied in Asian populations. We investigated the associations of PRS with AD neuroimaging biomarkers and cognitive phenotypes in a Korean Cohort. Method: The study included 501 older adults (264 cognitively normal [CN], 146 mild cognitive impairment [MCI], and 91 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). Comprehensive clinical and neuropsychological evaluations, as well as multi‐modal neuroimaging including 3T MRI and 11C‐PiB‐PET were administered. A subset of participants underwent 18F‐AV‐1451 PET (n = 167). Imaging phenotypes including beta‐amyloid (Aβ) positivity, global tau deposition, and adjusted hippocampal volume (HVa) were used for amyloid (A), tau (T), and neurodegeneration (N) biomarkers, respectively., which was imputed using the TOPMed reference panel. PRS was calculated using the summary statistics of a recent large‐scale GWAS study for AD by PRS‐CS. The Apolipoprotein E (APOE) region was excluded in the calculation. The associations between standardized PRS and imaging/cognitive phenotypes were examined using either multiple linear or logistic regression analysis with covariates (age and sex for neuroimaging biomarker phenotypes; age, sex and education for cognitive phenotypes). Result: PRS was significantly higher in the AD dementia group compared to the CN group. Higher PRS was associated with greater CDR‐sum‐of‐boxes (β[SE] = 0.233[0.083], t = 2.818, p = 0.005) and lower MMSE scores (β[SE] = ‐0.648[0.198], t = ‐3.271, p = 0.001). In terms of AD neuroimaging biomarkers (Figure 1), higher PRS was significantly associated with an increased likelihood of Aβ positivity (OR = 1.233, 95%CI = 1.024‐1.491), and lower HVa (β[SE] = ‐132.79[49.624], t = ‐2.676, p = 0.008), but not with global tau deposition (β[SE] = 0.075[0.048], t = 1.573, p = 0.118). Conclusion: These findings suggest that higher PRS predicts increased pathological Aβ deposition and accelerated neurodegeneration, as well as greater cognitive decline. Further investigation in larger and multiethnic samples are needed to determine generalizability to other ethnoracial populations. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) has been reported to reduce the risk of Alzheimer's disease (AD) dementia and related cognitive decline. We aimed to investigate the influence of PA on the progression from cognitively normal (CN) status to mild cognitive impairment (MCI) or from MCI to AD dementia in non‐demented older adults. Method: This study included 194 non‐demented (148 CN and 46 MCI) participants from the Korean Brain Aging Study for Early diagnosis and prediction of Alzheimer's disease (KBASE), who completed both baseline and 2‐year follow‐up clinical evaluation. At baseline, the participants underwent comprehensive clinical and neuropsychological assessment, multimodal brain imaging including [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET and MRI, and current PA measured using the Lifetime Total Physical Activity Questionnaire. Result: After 2 years, five CN and 22 MCI participants progressed to MCI and AD dementia, respectively. Logistic regression analyses showed that high current PA (above the median value) reduced the risk of the progression from MCI to AD dementia even after controlling age, sex, education, apolipoprotein E e4 positivity, baseline brain amyloid deposition, AD‐signature region glucose metabolism, and AD‐signature region cortical thickness (Bonferroni corrected p‐value = 0.028). In contrast, PA had no effect on the progression from CN to MCI. Conclusion: The findings suggest that a physically active lifestyle in late‐life reduces the risk of conversion to AD dementia in MCI independently of AD‐related brain pathologies. [ABSTRACT FROM AUTHOR]

Background: Our previous work reported that mild cognitive impairment (MCI) patients with multiple mild behavioral impairment (MBI) domain symptoms (complex group) revealed a higher risk of developing Alzheimer's disease (AD) compared with those with no MBI symptoms (asymptomatic group) and cortical thinning in the parietal and frontal areas. However, MCI patients with only affective dysregulation (affective dysregulation group) were not associated with the risk of AD and revealed relative cortical thickening (Yoon EJ, Front Aging Neurosci 2023). To clarify relationships of cortical thickness changes and risk of progression to AD in MCI patients, we compared structural covariance patterns between hippocampal volume and cortical thickness among the MBI subgroups. Method: A total 201 older adults with amnestic MCI were classified based on profiles of MBI domain symptoms into asymptomatic, affective dysregulation, and complex groups. The FreeSurfer was used to estimate cortical thickness and volumes of hippocampal subfields (Fig 1). A vertex‐wise general linear interaction model was used to compare group map of covariance between volumes of hippocampus subfields and thickness at each of vertices. Correlations between the thickness in regions showing significant group differences and mini‐mental state examination (MMSE) scores were also assessed. Result: In the affective dysregulation group, the structural covariance of left CA1, CA4/DG and molecular layer were increased in the left superior and inferior parietal cortex (Fig 2a), and the thickness of this region showed positive correlation with MMSE (spearman's rho = 0.302, p‐value = 0.046). The structural covariance of left hippocampal tail for the affective dysregulation group was increased in left lateral occipital cortex, and those for the complex group was increased in left inferior parietal and lateral occipital cortex compared with the asymptomatic group (Fig 2b). Also, the complex group revealed decreased structural covariance of right subiculum with left rostral middle frontal cortex (Fig 2c). Conclusion: Our findings suggest that the lateral parietal area might have an important role in compensatory mechanisms in the affective dysregulation group. On the other hand, the complex group may be associated with more advanced stages of disease in which the patterns of increased covariance of hippocampal subfields were disappeared or inversed. [ABSTRACT FROM AUTHOR]

Background: Primary age‐related tauopathy (PART) is a neuropathological entity with neurofibrillary tangles in the absence of beta‐amyloid plaques in the brain. Recent advances in neuroimaging made it possible to identify amyloid PET‐negative (A‐) tau PET‐positive (T+) condition as a possible candidate for PART in living human brains. We tried to investigate neurodegenerative biomarkers of A‐T+ older adults compared to those of A+T+ and A‐T‐ [corresponding to Alzheimer's disease (AD) and no AD pathology, respectively] individuals. Method: A total of 156 older participants (64 cognitively normal, 43 mild cognitive impairment (MCI), and 49 dementia), were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE). All participants underwent comprehensive clinical evaluation and multimodal brain imaging including amyloid and tau PET, and MRI. Global PiB retention measured by 11C‐PiB‐PET and tau deposition in the regions corresponding to Braak stages measured by 18F‐AV‐1451 PET were used in this study. A+ was defined as global mean Aβ deposition standardized uptake value ratio (SUVR) > 1.4 and T+ was defined as tau burden corresponding to Braak stages I/II, III/IV, or V/VI. Hippocampal volume, AD‐signature cortical thickness (AD‐CT), AD‐signature cerebral glucose metabolism (AD‐CM) and white matter hyperintensity (WMH) volume were also measured as neurodegenerative biomarkers. Multiple linear regression analysis controlling for age, gender, and APOE ε4 positivity was used to investigate the group differences of neurodegenerative biomarkers. Result: Of the 156 participants, 31 were defined as A‐T‐, 53 as A+T‐, and 72 as A+T+. A‐T+ group had higher levels of hippocampal volume (B = 683.448, p<0.001), AD‐CT (B = 0.267, p<0.001) and AD‐CM (B = 0.174, p<0.001), but not WMH volume (B = ‐1.188, p = 0.651), compared to A+T+ group. When compared to A‐T‐ group, A‐T+ group did not show significant difference in any of the neurodegenerative biomarkers. Conclusion: Our findings suggest that, in regard of neurodegeneration, older adults with A‐T+ condition, close to pathological PART, are less severe than those with A+T+, while they appear similar to those with A‐T‐. [ABSTRACT FROM AUTHOR]

Background: Growing evidences suggest that degeneration of cerebral white matter (WM) occurs in Alzheimer's disease (AD) independently of cerebrovascular risks or injury. Previous studies using diffusion tensor imaging (DTI) have reported a loss of WM microstructural integrity in the corpus callosum (CC) and cingulum (CG) in AD dementia and mild cognitive impairment (MCI). However, only limited information is available for the relationship of in vivo AD‐specific pathologies including beta‐amyloid (Aβ) and tau accumulation with WM microstructal alterations. Thus, we aimed to examine the association between in vivo AD pathologies and microstructural integrity of the CC and CG through cross‐sectional and longitudinal approaches. Method: A total of 170 (74 cognitively normal, 58 MCI, and 38 AD dementia) older adults from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. All participants underwent comprehensive clinical assessment and multi‐modal brain imaging including [11C]‐Pittsburgh‐Compound‐B‐positron emission tomography (PET), 18F‐AV‐1451 PET, and DTI. The mean fractional anisotropy (FA) values were obtained for 2 regions of interests, the CC and CG on DTI. The data was analyzed using linear regression model adjusted for age, sex, APOE4 positivity, and vascular risk factor score. Regression‐based mediation analysis was also conducted to assess the mediation of tau for the relationship between Aβ and FA. Result: In cross‐sectional analyses for baseline data, global tau deposition had a significant negative association with both CC and CG FA (β = ‐0.013, p = 0.004 and β = ‐0.011, p = 0.002), while global Aβ retention showed a negative association with only CG FA (β = ‐0.015, p = 0.004). Longitudinal analyses revealed that higher tau deposition at baseline was associated with both greater reduction of both CC and CG FA over 2 years (β = ‐0.010, p = 0.001 and β = ‐0.005, p = 0.046), whereas Aβ was associated with neither CC nor CG FA change over the period. Additional mediation analysis demonstrated that the cross‐sectional association between Aβ and CG FA was mediated by tau deposition, while there was no direct relationship between the two. Conclusion: Our findings suggest that regional alterations of WM microstructural integrity in MCI and AD dementia, which occurs independently of vascular risks, are mainly related with tau pathology rather than amyloid pathology. [ABSTRACT FROM AUTHOR]

Background: Interest in the role of Herpes Simplex Virus (HSV) infection in the pathogenesis of Alzheimer's disease (AD) has increased in recent years. However, previous studies yielded inconsistent findings and no studies have yet investigated the relationship between HSV infection and in vivo AD pathologies such as beta‐amyloid (Aβ) and tau deposition in brain. We examined whether the level of serum anti‐HSV immunoglobulin G (IgG) antibodies (HSV‐IgG), an index of past infection of HSV, is associated with in vivo Aβ and tau deposition in nondemented individuals. We also investigated the modulating effect of HSV‐IgG titer on the relationship between Aβ and tau deposition. Method: A total of 426 nondemented older individuals (55‐90 years old) were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. All participants underwent comprehensive clinical assessment, [11C]‐Pittsburgh Compound B positron emission tomography (PET), and blood sampling for measurement of serum HSV antibodies. A subset of participants (N = 129) underwent [18F] AV‐1451 PET. Individuals whose HSV‐IgG titer was lower than 25 percentile of the whole group was classified as the HSVlow group, while those with HSV‐IgG titer higher than 25 percentile were classified as the HSVhigh group. Result: There was no significant difference in age, sex, clinical diagnosis (cognitive normal vs. mild cognitive impairment), and apolipoprotein E e4 positivity (APOE4) between the HSVlow (N = 106) and HSVhigh (N = 320) groups. In terms of AD biomarkers, neither global Aβ nor tau deposition was different between the HSVhigh and HSVlow groups, even after controlling the effect of age, sex, and APOE4. However, there was a significant HSV group x Aβ deposition interaction effect on tau deposition (p = 0.037), suggesting the level of HSV‐IgG modulates the relationship between Aβ and tau deposition. Subsequent subgroup analyses showed a significant positive association between Aβ and tau deposition only in the HSVhigh group (p < 0.001), but not in the HSVlow group. Conclusion: Our finding suggests that past HSV infection may aggravate the influence of Aβ on tau deposition. In regard of AD prevention, the result also supports that more attention needed to be paid to controlling HSV infection. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported the associations between vitamin D deficiency and increased risk of Alzheimer's disease (AD) dementia in older adults, but little is known how vitamin D is involved in the pathophysiology of AD. Thus, we aimed to examine the association and interaction of serum vitamin D level with in vivo AD pathologies including beta‐amyloid (Aβ) and neurodegeneration in nondemented older adults. Method: Nondemented older adults consisting of cognitively normal and mild cognitive impairment groups were recruited from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25(OH)D, and multimodal brain imaging including Pittsburgh compound‐B (PiB) positron emission tomography and magnetic resonance imaging at baseline. Global PiB retention was measured for Aβ biomarker, and hippocampal volume adjusted for intracranial volume (HVa) was used for neurodegeneration biomarker. Age, sex, apolipoprotein E (APOE) e4 positivity was controlled as covariates in all analyses. Result: A total 428 participants (mean age [SD]: 70.54 [7.97], female [N, %]: 182 [43%]) were included for analysis. Serum 25(OH)D levels were directly associated neither Aβ deposition nor HVa. However, serum 25(OH)D level had significant moderation effect on the association between Aβ and hippocampal neurodegeneration, in that lower serum 25(OH)D level significantly exacerbate the negative association between global Aβ retention and HVa (β = 34.612, p = 0.008) (Figure). Conclusion: The present findings suggest that lower serum vitamin D level may increase AD dementia risk by aggravating Aβ‐related neurodegeneration. [ABSTRACT FROM AUTHOR]

Ferroelectricity in HfO2 thin films can be utilized for fast, power‐efficient, and highly scalable non‐volatile memories. However, the required wake‐up process for inducing ferroelectricity/ achieving higher polarization is one of the major hurdles that hinder HfO2‐based thin films from developing reliable electronic devices. The wake‐up effect is believed to originate from i) phase transformation from non‐ferroelectric to ferroelectric, ii) movement of defect entities (mainly oxygen vacancy defects) near the film‐electrode interface, and iii) heterogeneity of the electrode interfaces. In the present study, an experimental strategy is designed to overcome these sources of the wake‐up process. A multi‐step deposition and annealing process is carried out to induce wake‐up‐free ferroelectricity in Yttrium doped HfO2 (Y:HfO2) thin film directly grown on Si‐substrate. Furnace annealing is utilized instead of the standard rapid thermal annealing process to reduce the oxygen deficiencies and stimulate the direct growth of the polar Y:HfO2. The oxygen‐vacancy‐related defects are found to be the dominating source of wake‐up effect in Y‐doped HfO2 films. The step‐wise deposition and annealing in the oxygen atmosphere facilitate direct growth of the polar phase, reduce the oxygen vacancies, and induce wake‐up‐free ferroelectricity in Y:HfO2. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's disease (BD) remains unclear. This study was performed to investigate the associations between metabolic syndrome and risk of BD using nationwide population data. We conducted a retrospective cohort study of 10 505 818 Korean subjects who received health checkups in 2009–2012. Patients were classified into a MetS and its components group and were followed‐up until 2016 for new‐onset BD. A Cox proportional hazards model was used to assess the independent or synergistic effects of MetS and its components on the risk of incident BD. Compared to subjects without MetS components, the hazard ratio (HR) for development of BD in patients with MetS was 0.874 (95% confidence interval [CI]: 0.819–0.933) and this association was more prominent when all components of MetS were present (HR = 0.675, 95% CI = 0.571–0.798). Subjects with low high density lipoprotein (HDL) has a significantly increased risk of the development of BD (HR = 1.51, 95% CI = 1.4–1.594) compared to controls. This study showed that the incidence of Behçet's disease was reduced in subjects with MetS. Moreover, the presence of MetS components, with the exception of HDL, was negatively related to the development of BD. [ABSTRACT FROM AUTHOR]

Aim: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD‐related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid‐beta (Aβ) burden, AD‐signature regional neurodegeneration, and white matter hyperintensities (WMH) in non‐demented middle‐ and old‐aged adults. Methods: A total of 397 non‐demented participants underwent comprehensive clinical and neuropsychological assessments, 11C‐labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five‐Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. Results: Neither neuroticism nor conscientiousness was associated with cerebral Aβ deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD‐signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD‐signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aβ deposition or WMH were not. Conclusion: The present findings suggest that amyloid‐independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD. [ABSTRACT FROM AUTHOR]

Imatinib (Gleevec) is a multiple tyrosine kinase inhibitor that decreases the activity of the fusion oncogene called BCR‐ABL (breakpoint cluster region protein‐Abelson murine leukemia viral oncogene homolog) and is clinically used for the treatment of chronic myelogenous leukemia and acute lymphocytic leukemia. Small molecule drugs, such as imatinib, can bind to several cellular proteins including the target proteins in the cells, inducing undesirable effects along with the effects against the disease. In this study, we report the synthetic optimization for 14C‐labeling and radiosynthesis of [14C]imatinib to analyze binding with cellular proteins using accelerator mass spectroscopy. 14C‐labeling of imatinib was performed by the synthesis of 14C‐labeld 2‐aminopyrimidine intermediate using [14C]guanidine·HCl, which includes an in situ reduction of an inseparable byproduct for easy purification by HPLC, followed by a cross‐coupling reaction with aryl bromide precursor. The radiosynthesis of [14C]imatinib (specific activity, 631 MBq/mmol; radiochemical purity, 99.6%) was achieved in six steps with a total chemical yield of 29.2%. [ABSTRACT FROM AUTHOR]

Background: Recent evidences suggest that the use of antihypertensive medications (HTNmed) may decrease the incidence of Alzheimer's disease (AD) dementia. We investigated whether the use of HTNmed is associated with in vivo AD pathologies, particularly cerebral beta‐amyloid (Aβ) deposition, and whether the relationship between HTNmed and cerebral Aβ deposition differs according to the characteristics of HTNmed in older adults. Method: Participants were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. Both cognitively normal and cognitively impaired older adults (age range: 55‐90 years) who met the following criteria of hypertension (HTN) were included for this study: i) clinical diagnosis of hypertension or ii) systolic blood pressure higher than 130mmHg or diastolic blood pressure higher than 80mmHg measured at baseline. All participants underwent comprehensive clinical assessment and [11C] Pittsburgh Compound B positron emission tomography PET for measuring Aβ deposition. Result: Among total 413 older adults with hypertension, 227(54.8%) were taking HTNmed. Overall, individuals taking HTNmed showed significantly lower Aβ deposition compared to those without HTNmed (B = ‐0.104, p = 0.007), even after controlling age, sex, apolipoprotein E e4 positivity, and mean arterial blood pressure(MAP). Drug‐class specific analyses showed that the use of renin angiotensin system (RAS) inhibitor (i.e., angiotensin converting enzyme inhibitor and angiotensin receptor blocker) was associated with less cerebral Aβ deposition among older adults with HTNmed (B = ‐0.142, p = 0.006), but the use of other HTNmeds was not. In addition, the blood‐brain barrier permeability of HTNmed also did not have any relationship with Aβ deposition. Conclusion: The present finding suggests that the use of HTNmed, particularly RAS inhibitor, is associated with less Aβ deposition in older adults with hypertension. Further studies to explore the mechanism underlying the effect of RAS inhibitor on Aβ accumulation may provide clues for new therapeutic targets of AD. [ABSTRACT FROM AUTHOR]

Background: In the present study, we aimed to confirm the association between speech characteristics of individuals with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) and brain regions, and to investigate the neurobiological basis of speech‐based AD detection. Method: Individuals with MCI (n = 13, age = 78.3), mild‐to‐moderate AD (n = 12, age = 77.8) underwent a structural MRI scan and engaged in three speech tasks: an interview, sentence repetition, and paragraph recall. From the speech samples, we extracted frequency‐related, intensity‐related, and temporal features which were found to be altered in the course of AD and MCI pathology. We selected nine regions of interest (ROI) which were found to be involved in speech production and reduced in MCI and AD pathology; the Inferior Frontal Gyrus (IFG), the Medial Frontal Gyrus (MFG), the Precuneus, the Inferior Parietal Lobe (IPL), Inferior Temporal Gyrus (ITG), Medial Temporal Gyrus (MTG), the Superior Temporal Gyrus (STG), the Fusiform Gyrus (FFG), and the Cerebellum. The linear mixed‐effect analysis was used to identify the associations between speech features and regional brain volumes. Result: The Left IPL (χ2 (1) = 7.69, corrected P = 0.033), the Right ITG (χ2 (1) = 11.5, corrected P = 0.0128) the Right FFG (χ2 (1) = 9.35, corrected P = 0.0198) reduced the pitch of voice by about 0.887 ± 0.292, 1.368 ± 0.329, and 1.69 ± 0.429 respectively. The associations between the Right FFG (χ2 (1) = 4.58, corrected P = 0.0900), Left FFG (χ2 (1) = 5.87, corrected P = 0.0675) and loudness were marginally significant, with the reduction of volumes in the Right FFG and Left FFG decreasing the loudness by 0.096 ± 0.041, and 0.1165 ± 0.0454. The marginally significant associations were observed between the Right IPL (χ2 (1) = 4.75, corrected P = 0.0900), the Left FFG (χ2 (1) = 0.39, corrected P = 0.53) and the speech rate, and the atrophy of brain regions decreased the speech rate by 0.0824 ± 0.0363, 0.0535 ± 0.0079. Conclusion: The present study identified the associations between speech biomarkers and regional brain volumes providing clinical validity for the speech‐based Alzheimer's disease detection. [ABSTRACT FROM AUTHOR]

Background: Mild Behavioral Impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at‐risk state for dementia (Ismail Z, Alzheimers Dement, 2016). However, the associations between MBI and a risk of phenocoversion to dementia and its neuroanatomical correlates in MCI are still unclear. Method: A total 1326 older adults with MCI was followed for a mean of 3.0 ± 2.0 years. MBI was approximated using a transformation algorithm for the neuropsychiatric inventory at baseline. Two‐step cluster analysis was used to explore classes of 5 MBI domains (decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, abnormal perception/thought content). A Cox regression analysis was applied to investigate the association between the clusters and phenoconversion to AD. A subset of participants (n = 225) underwent 3D T1‐weighted MRI scans and cortical thickness was compared among the clusters of MBI domains. Result: The cluster analysis identified 3 groups of participants: (1) people without MBI (47.8%, asymptomatic); (2) people with only affective dysregulation (29.3%, affective dysregulation); (3) people with relatively high probability of affective dysregulation, followed by impulse dyscontrol and affective dysregulation (22.9%, multiple domains). Compared to the asymptomatic, multiple domains was associated with a higher risk of phenoconversion to AD (hazard ratio = 2.589 [1.981 – 3.385], p = < 0.001), but affective dysregulation did not predict phenoconversion (1.204 [0.896 – 1.620], p = 0.219) (Fig 1). MCI individuals with symptoms in multiple domains revealed thinning in the bilateral superior and inferior parietal, superior temporal, and prefrontal cortex, and the right precuneus compared to those with only affective dysregulation (Fig 2). We did not find differences in cortical thickness between phenocoverter and non‐phenoconverter, and interaction of clusters of MBI domains and phenoconversion. Conclusion: The multiple co‐occuring MBI domains in individuals with MCI are associated with a higher risk of phenoconversion to AD. Moreover, MCI individuals with symptoms in multiple domains revealed cortical thinning in the superior parietal and precuneus, which have suggested as AD signatures (Dickerson BC, Cereb Cortex, 2009). These results suggest that evaluation of MBI and neuroimaging characteristics could be useful for risk stratification in MCI individuals. [ABSTRACT FROM AUTHOR]

A novel solid‐phase microextraction Arrow was used to separate volatile organic compounds from soy sauce, and the results were verified by using gas chromatography with mass spectrometry. Solid‐phase microextraction Arrow was optimized in terms of three extraction conditions: type of fiber used (polydimethylsiloxane, polyacrylate, carbon wide range/polydimethylsiloxane, and divinylbenzene/polydimethylsiloxane), extraction temperature (40, 50, and 60°C), and extraction time (10, 30, and 60 min). The optimal solid‐phase microextraction Arrow conditions were as follows: type of fiber = polyacrylate, extraction time = 60 min, and extraction temperature = 50°C. Under the optimized conditions, the solid‐phase microextraction Arrow was compared with conventional solid‐phase microextraction to determine extraction yields. The solid‐phase microextraction Arrow yielded 6–42‐fold higher levels than in solid‐phase microextraction for all 21 volatile organic compounds detected in soy sauce due to the larger sorption phase volume. The findings of this study can provide practical guidelines for solid‐phase microextraction Arrow applications in food matrixes by providing analytical methods for volatile organic compounds. [ABSTRACT FROM AUTHOR]

We screened a variety of natural products against MERS-CoV as an attempt of developing I anti i -MERS-CoV drugs, and many flavonoids showed I anti i -MERS activities. Total 12 compounds of bavachinin derivatives in four core structures were evaluated to figure out their I anti i -MERS-CoV activity and cell-cytotoxicity by cellular phenotypic screening method as shown in Table. B 2a b was prepared by hydrogenations of external double bonds of B 1a b , which showed the best I anti i -MERS activities regardless of their I O i -substituents. The I anti i -MERS activity of B 6a b was a little decreased compared to B 1a b , however, the I anti i -MERS activities of its derivatives were conserved. [Extracted from the article]

Aim: We investigated the effects of metformin on cognitive function in a prospective cohort of older adults. Methods: Participants aged ≥60 years were selected, and their Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment, including the Mini‐Mental State Examination, and activities of daily living were evaluated prospectively. Rapid deterioration of cognitive function was defined as annual change of test scores in the lowest quartile. Results: A total of 732 participants (mean age 76.7 ± 6.6 years) were followed up for 2.9 years (interquartile range 1.0–5.7 years). A linear mixed model showed that diabetes was associated with significant deterioration of Verbal Delayed Free Recall and Recognition scores (P = 0.007 and 0.022, respectively). Among diabetes patients, metformin treatment was not associated with changes of any Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component or activities of daily living index. However, rapid deterioration of Mini‐Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin‐taking group, even after adjustment for age, sex, education level, baseline cognitive function, baseline glycated hemoglobin levels, renal and liver function, body mass index, hypertension, dyslipidemia, antidiabetic agents other than metformin, and baseline brain imaging abnormality (odds ratio 4.47, 95% confidence interval 1.24–16.05 and odds ratio 7.37, 95% confidence interval 1.19–45.56). Conclusions: Metformin treatment was not associated with changes of any of Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component scores or activities of daily living index. However, rapid deterioration of Mini‐Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin‐treated group. Geriatr Gerontol Int 2019; 19: 755–761. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease known to be associated with a variety of systemic comorbidities, such as metabolic syndrome and obesity. Obesity represents a major comorbidity and has been suggested to be related to psoriasis. This nationwide population‐based prospective cohort study was performed to investigate the impacts of body mass index (BMI) and waist circumference (WC) on psoriasis. We used the health check‐up database and the study population consisted of subjects who had undergone health screening between January 2009 and December 2012. This study investigated patients newly diagnosed with psoriasis (International Classification of Disease, Tenth Revision, code L40) by dermatologists during the follow‐up period (5.32 years), based on claims data. The total population consisted of 22 633 536 subjects, among whom 399 461 had newly developed psoriasis. Subjects with BMI of more than 30 had a higher risk of psoriasis (hazards ratio [HR], 1.118; 95% confidence interval [CI], 1.100–1.137) compared with the BMI 18.5–23 group. WC showed a dose‐dependent association with psoriatic risk. Subjects with WC over 105 cm showed the highest risk of psoriasis (HR, 1.305; 95% CI, 1.261–1.349) compared with subjects with WC lower than 80/75 after adjusting for confounding factors, including BMI. The risk of psoriasis was highest in males with normal BMI and abdominal obesity (HR, 1.175; 95% CI, 1.150–1.200). Our study indicates that WC is a specific factor affecting psoriatic risk and highlights the association between abdominal obesity and psoriasis, thus increasing awareness of the role of abdominal obesity in the pathogenesis and comorbidities of psoriasis. [ABSTRACT FROM AUTHOR]

The relationship between psoriasis and cancer has not yet been established. The aim of this study was to evaluate the association of psoriasis with certain cancers using national statistics. All patients with psoriasis (n = 892 089; 51.7% male) and age‐ and sex‐matched control subjects (n = 4 460 445) at a 5:1 ratio were enrolled using data from the National Health Insurance Service between 2007 and 2014 in Korea. In psoriatic subjects, overall cancer risk was higher than for subjects without psoriasis after adjusting for income level, diabetes, hypertension, dyslipidemia and place of residence (hazard ratio, 1.065; 95% CI, 1.049–1.081). The risk of cancer increased in the following order: prostate, thyroid, liver, ovarian, lung, leukemia, skin, multiple myeloma, lymphoma and testicular. The severity and sex of psoriatic patients also had different cancer risks. In psoriatic patients, a slightly increased risk for specific malignant neoplasms was shown. Therefore, periodic screening for cancer risk is recommended in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Recently, herpes zoster (HZ) has been identified as a risk factor for stroke, but there have been few studies on the relationship between HZ and other cardiovascular diseases (CVD), including myocardial infarction (MI) and heart failure (HF). The purpose of this study was to investigate the risk of HZ occurrence after CVD and the occurrence of CVD after HZ. This was a retrospective case–control study based on the National Health Insurance System claims database for 20 311 patients with HZ and 13 980 patients with CVD and 1:5 age‐ and sex‐matched control subjects for each from January 2006 to December 2013. We evaluated the reciprocal relationship between HZ and CVD including MI, ischemic stroke and HF. Severe HZ requiring hospitalization independently increased the risk of subsequent MI (hazard ratio [HR], 1.831; 95% confidence interval [CI], 1.354–2.476)], ischemic stroke (HR, 1.523; 95% CI, 1.212–1.915) and HF (HR, 2.034; 95% CI, 1.615–2.562) during the study period. Likewise, patients with an episode of MI, ischemic stroke or HF were also at increased risk of HZ hospitalization (after MI: HR, 1.625; 95% CI, 1.144–2.308; after stroke: HR, 1.518; 95% CI, 1.177–1.957; and after HF: HR, 1.485, 95% CI 1.041–2.117). Our results suggest that there is a significant reciprocal relationship between severe HZ requiring hospitalization and CVD including MI, ischemic stroke and HF. [ABSTRACT FROM AUTHOR]

Background: While previous studies consistently reported regional microstructural changes of the cerebral white matter (WM) in Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI), little information is available for such changes in the preclinical stage of AD. We first aimed to investigate regional microstructural alteration of the WM in cognitively normal (CN) older adults with amyloid‐beta (Aβ) deposition. We also tried to develop a prediction model for Aβ positivity in CN using information on WM microstructural alteration and clinical variables that can be easily obtained in memory clinics. Method: Seventy‐five CN older adults from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease (KBASE) cohort were included in the analyses. All Participants underwent comprehensive clinical and neuropsychological assessment, T1 MRI, diffusion tensor imaging (DTI), and [11C]PiB‐PET. All CN subjects were divided into Aβ positive (CN+) and negative (CN‐) based on the level of cerebral Aβ retention on [11C]PiB‐PET. Multivariate stepwise logistic regression analyses were conducted to develop Aβ positivity prediction models. Result: When compared to CN‐, CN+ showed high mean diffusivity (MD) value of the genu of the corpus callosum (CC_genu) (F(1,73) = 6.357, p = 0.014, Figure 1). The area under the curve (AUC) of the receiver operating characteristics curve for the Aβ positivity prediction model only using MD of the CC_genu was 0.653 [confidence interval (CI) = 0.511‐0.794]. Model with MD of the CC_genu, age, and word list recall and constructional recall test scores were finally selected. The AUC of the final model was 0.851 [CI = 0.765‐0.937] (Figure 2). Conclusion: The findings indicate that microstructural alteration of the CC_genu occurs even in the stage of preclinical AD. When taken together with episodic memory scores commonly available in clinical practice, information about such regional WM microstructural alteration can be used to screen preclinical AD. [ABSTRACT FROM AUTHOR]

Abstract: The preparation of ferroelectric polymer–metallic nanowire composite nanofiber triboelectric layers is described for use in high‐performance triboelectric nanogenerators (TENGs). The electrospun polyvinylidene fluoride (PVDF)–silver nanowire (AgNW) composite and nylon nanofibers are utilized in the TENGs as the top and bottom triboelectric layers, respectively. The electrospinning process facilitates uniaxial stretching of the polymer chains, which enhances the formation of the highly oriented crystalline β‐phase that forms the most polar crystalline phase of PVDF. The addition of AgNWs further promotes the β‐phase crystal formation by introducing electrostatic interactions between the surface charges of the nanowires and the dipoles of the PVDF chains. The extent of β‐phase formation and the resulting variations in the surface charge potential upon the addition of nanowires are systematically analyzed using X‐ray diffraction (XRD) and Kelvin probe force microscopy techniques. The ability of trapping the induced tribocharges increases upon the addition of nanowires to the PVDF matrix. The enhanced surface charge potential and the charge trapping capabilities of the PVDF–AgNW composite nanofibers significantly enhance the TENG output performances. Finally, the mechanical stability of the electrospun nanofibers is dramatically enhanced while maintaining the TENG performances by applying thermal welding near the melting temperature of PVDF. [ABSTRACT FROM AUTHOR]

The 68Ga is a positron‐emitting radionuclide that can be combined with bifunctional chelating agents and bioactive substances for use as positron‐emission tomography (PET) diagnostic agents. The HBED‐CC is an acyclic chelating agent that is rapidly labeled with 68Ga under mild conditions. To target cancer cells, bioactive substances can be conjugated to the carboxyl terminus of HBED‐CC. Because folic acid strongly binds to folate receptors that are overexpressed on the surfaces of many types of cancer cells, it was coupled with HBED‐CC through a small polyethylene glycol‐based linker (EDBE) to generate an active, receptor‐selective targeting system. The HBED‐CC‐EDBE‐folate (HCEF) precursor was readily labeled with 68Ga in 5 minutes at room temperature (98% radiochemical yield; 99% radiochemical purity after isolation). In cellular uptake tests, higher uptakes of 68Ga‐HCEF were observed for the CT26 and KB cell lines (which express folate receptors) than for the A549 cell line (which does not). Finally, in vivo micro‐PET measurements over 2 hours of binding in BALB/c mice into which CT26 tumors had been transplanted showed the selective accumulation of 68Ga‐HCEF in the folate receptor‐expressing CT26 tumors. These results confirmed the potential of 68Ga‐HCEF as a PET diagnostic agent for tumors that express folate receptors. [ABSTRACT FROM AUTHOR]

Background: Depression is a common manifestation of Alzheimer's disease (AD) and frequently observed at the early phase of the disease. Several postmortem studies demonstrated that tau deposition was found at the brainstem nuclei including the locus coeruleus (LC) and dossal raphe nucleus (DRN) (3, 4), even before early Braak stages of neurofibrillary tangle pathology. Given the disturbance of monoaminergic system is related to depression in general, tau deposition in the LC or DRN may underlie depression in late‐life, as suggested in a couple of postmortem studies. In this context, we tried to examine the hypothetical association between in vivo tau depostion at the brain stem monoaminergic nuclei and depression in cognitively unimpaired older adults. Method: A total of 69 cognitively unimpaired older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. All participants underwent comprehensive clinical assessment including the Hamilton Rating Scale for Depression (HRSD) and [18F] AV‐1451 positron emission tomography. Tau deposition in the LC and DRN was measured using the Harvard Ascending Arousal Network Atlas (AAN). Tau deposition in the pons was also assessed as a non‐monoaminergic control for comparison. Age, education, sex, and apolipoprotein E ε4 positivity were controlled as covariates in the analyses for the association between brain stem tau and HRSD score. Result: Tau deposition in the LC was significantly associated with HRSD total score (β = 3.861, P =.009). In contrast, there was no significant association between tau deposition in the DRN and HRSD score (β = 2.229, P =.090). Tau deposition in the pons was also not related to HRSD score (β = 1.632, P =.207). Conclusion: The findings support the possibility that alteration of the noradrenergic neurons in the LC by tau pathology may underlie depressive manifestation in cognitively unimpaired older individuals. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The characteristics and underlying mechanisms of tinnitus remain more elusive in the pediatric population than in adults. We investigated the prevalence of tinnitus, its characteristics, and associated factors, with a focus on psychoemotional problems in adolescents.Study Design: Cross-sectional study METHODS: In total, 962 adolescents were surveyed for tinnitus and possibly related otologic and socioeconomic factors. The participants completed a visual analog scale (VAS) pertaining to various aspects of tinnitus, as well as the Tinnitus Handicap Inventory, Children's Depression Inventory (CDI), State Anxiety Inventory for Children, Trait Anxiety Inventory for Children (TAIC), Internet Addiction Test, Conners' Abbreviated Parent Rating Scale, and a learning disability score. Characteristics of tinnitus were analyzed, and psychoemotional and other factors were compared between tinnitus and nontinnitus groups.Results: Approximately one-third of subjects reported experiencing tinnitus. A family history of tinnitus, subjective hearing loss, dizziness, and CDI and TAIC abnormalities were significantly associated with tinnitus. In the tinnitus-always group, tinnitus showed significant relationships with subjective hearing loss, bilateral tinnitus, and VAS, CDI, and TAIC scores.Conclusions: The results suggest that about one-third of adolescents experience tinnitus, which may be related to psychoemotional factors. In particular, anxiety and depression may be important factors to consider in managing tinnitus in adolescents. Further study of tinnitus in adolescents, including efforts toward diagnosis and management, is needed to determine whether there is a causal relationship with anxiety and depression, and the extent to which adverse outcomes may be associated with these psychoemotional factors.Level Of Evidence: 4 Laryngoscope, 127:2113-2119, 2017. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported the link between apolipoprotein E (apoE) in peripheral blood and risk of Alzheimer's disease (AD) dementia. However, underlying mechanism for this link remains unclear. We investigated whether serum apoE concentration is associated with in vivo AD pathologies in nondemented older adults. Method: A total 437 nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. All participants underwent comprehensive evaluation including clinical assessment, blood sampling, as well as 11C‐PiB PET and MRI. A subset of participants (N=130) also underwent 18F‐AV1451 PET for measurement of brain tau pathologies. All participants were divided into low, middle, and high apoE concentration tertile groups (i.e., T1, T2, and T3). Result: There were no significant differences in demographic and clinical variables except the frequency of female and rate of apoE ε4 allele (APOE4) positivity; the lower serum apoE was associated with fewer female (40.1%, 61.6%, and 67.8% for T1, T2, and T3, respectively) and higher APOE4 positivity rate (34.3%, 25.2%, and 16.8%). In terms of AD biomarker, Aβ positivity rate showed significant negative association with serum apoE (40.1%, 31.8%, and 24.8%), which remained significant after adjustment of covariates including age, sex, and diagnosis. In addition, reduced AD‐signature region volume, a neurodegeneration biomarker of AD, was significantly associated with lower serum apoE after controlling the same covariates. With regard to tau biomarker, positivity rate of global tau deposition showed significant negative association with serum apoE level (56.8%, 50%, and 20%) after adjustment of covariates. When we additively controlled the effect of APOE4 positivity, the associations between low serum apoE and greater neurodegeneration and tau positivity remained significant, whereas the association between apoE and Aβ positivity did not reach statistical significance. Conclusion: In the present study, low serum apoE was associated with greater burden of in vivo AD pathologies and such association appears even independent of APOE4 carrier status in regard of tau deposition and neurodegeneration. The finding suggests a potential role of serum apoE as a surrogate marker for in vivo AD pathologies in nondemented older adults. [ABSTRACT FROM AUTHOR]

Postburn pruritus is a common distressing sequela of burn wounds. Empirical antipruritic treatment often fails to have a satisfactory outcome, as the mechanism of it has not been fully elucidated. The aim of this study was to evaluate the manifestation of transient receptor potential vanilloid 3 (TRPV3), transient receptor potential ankyrin 1 (TRPA1), and other related receptors in postburn pruritus. Sixty-five burn patients with ( n = 40) or without ( n = 25) pruritus were investigated, including skin biopsies. Keratinocytes and fibroblasts from skin biopsy samples were separated. Real time-PCR showed that mRNA of TRPV3 was significantly increased in keratinocytes from pruritic burn scars than in keratinocytes from nonpruritic burn scars. With TRPV3 activation, intracellular Ca2+ concentrations were more significantly increased in keratinocytes from pruritic burn scars than in those from nonpruritic ones. Additionally, mRNA and protein levels of protease-activated receptor 2 (PAR2) and neurokinin-1 receptor (NK1R) were also significantly increased in pruritic burn scars. In conclusion, it was confirmed that TRPV3, PAR2, and NK1R were highly expressed in pruritic burn scars. These results may help determine a novel mechanism for postburn pruritus. [ABSTRACT FROM AUTHOR]

Introduction: Defective visual information processing contributes to visual hallucination in PD, for which "top-down" and "bottom-up" impairment are suggested mechanisms. This study was aimed to investigate macro- and microstructural neural changes in afferent visual pathways in relation to visual hallucination in nondemented PD patients.Methods: This study included 24 nondemented, nondepressed PD patients (10 hallucinating and 14 nonhallucinating) and 15 age-matched healthy controls. We analyzed volumetric and diffusion tensor MRI data by applying region of interest analyses on the visual pathways, including the optic chiasm, bilateral optic nerves, lateral geniculate bodies, optic radiations, and primary visual cortex.Results: Patients' demographic characteristics, daily medication doses, as well as duration and motor severity of PD were similar in the two PD groups. Compared to PD patients without hallucination, those with hallucination had fractional anisotropy decrease in the left optic nerve and showed atrophy of lateral geniculate bodies, especially in the left side. In addition, the PD with hallucination group had diffusivity increase in the left optic radiation compared to that in the PD without hallucination and healthy control groups. There were no differences in the primary visual cortex volume among the study groups.Conclusions: We found microstructural alterations in visual pathways in nondemented PD patients with hallucination, mainly in first-order neurons and atrophy in the lateral geniculate body where the retinal ganglion cells synapse to second-order neurons. Afferent visual pathway degeneration may occur in a trans-synaptic way in PD. Further studies warrant to be conducted. [ABSTRACT FROM AUTHOR]