Progesterone increases hepatic lipid content and plasma lipid levels through PR- B-mediated lipogenesis.

Progesterone (P4) is a crucial reproductive hormone that acts as a precursor for all other endogenous steroids. P4 modulates transcriptional activity during reproduction by binding to progesterone receptors (PR). However, the physiological role of P4 in the liver is understudied. P4-mediated lipid metabolism in the liver was investigated in this study, as P4 facilitates insulin resistance and influences energy metabolism. While exogenous lipids are mainly obtained from food, the liver synthesizes endogenous triglycerides and cholesterol from a carbohydrate diet. Hepatic de novo lipogenesis (DNL) is primarily determined by acetyl-CoA and its biosynthetic pathways, which involve fatty acid and cholesterol synthesis. While P4 increased the hepatic levels of sterol regulatory element-binding protein 1 C (SREBP-1 C), peroxisome proliferator-activated receptor-gamma (PPARγ), acetyl-CoA carboxylase (ACC), and CD36, co-treatment with the P4 receptor antagonist RU486 blocked these proteins and P4-mediated lipogenesis. RNA sequencing was used to assess the role of P4 in lipogenic events, such as fatty liver and fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism. P4 induced hepatic DNL and lipid anabolism were confirmed in the liver of ovarian resection mice fed a high-fat diet or in pregnant mice. P4 increased lipogenesis directly in mice exposed to P4 and indirectly in fetuses exposed to maternal P4. The lipid balance between lipogenesis and lipolysis determines fat build-up and is linked to lipid metabolism dysfunction, which involves the breakdown and storage of fats for energy and the synthesis of structural and functional lipids. Therefore, P4 may impact the lipid metabolism and reproductive development during gestation.

Artificial Intelligence-Enhanced Quantitative Ultrasound for Breast Cancer: Pilot Study on Quantitative Parameters and Biopsy Outcomes.

Traditional B-mode ultrasound has difficulties distinguishing benign from malignant breast lesions. It appears that Quantitative Ultrasound (QUS) may offer advantages. We examined the QUS imaging system's potential, utilizing parameters like Attenuation Coefficient (AC), Speed of Sound (SoS), Effective Scatterer Diameter (ESD), and Effective Scatterer Concentration (ESC) to enhance diagnostic accuracy. B-mode images and radiofrequency signals were gathered from breast lesions. These parameters were processed and analyzed by a QUS system trained on a simulated acoustic dataset and equipped with an encoder-decoder structure. Fifty-seven patients were enrolled over six months. Biopsies served as the diagnostic ground truth. AC, SoS, and ESD showed significant differences between benign and malignant lesions (p < 0.05), but ESC did not. A logistic regression model was developed, demonstrating an area under the receiver operating characteristic curve of 0.90 (95% CI: 0.78, 0.96) for distinguishing between benign and malignant lesions. In conclusion, the QUS system shows promise in enhancing diagnostic accuracy by leveraging AC, SoS, and ESD. Further studies are needed to validate these findings and optimize the system for clinical use.

miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease.

BACKGROUND: Alzheimer's dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. METHODS: We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N = 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N = 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification. RESULTS: Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and APOE ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs. CONCLUSIONS: Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.

CD133-containing microvesicles promote cancer progression by inducing M2-like tumor-associated macrophage polarization in the tumor microenvironment of colorectal cancer.

Tumor-associated macrophages (TAMs) are among the most abundant cell types in the tumor microenvironment (TME). The immunosuppressive TME formed by TAMs is an essential prerequisite for cancer progression. Tumor-derived microvesicles (MVs), a subtype of extracellular vesicle shed directly from the plasma membrane, are important regulators of intercellular communication and TME modulation during tumorigenesis. However, the exact mechanism by which tumor-derived MVs induce the generation of the immunosuppressive TME and polarization of TAMs remains unclear. Here, we investigated the role of CD133-containing MVs derived from colorectal cancer (CRC) cells in macrophage polarization and cancer progression. CD133-containing MVs from CRC cells were incorporated into macrophages, and M0 macrophages were morphologically transformed into M2-like TAMs. CD133-containing MVs were found to increase the mRNA expression of M2 macrophage markers. Additionally, cytokine array analysis revealed that M2-like TAMs induced by CD133-containing MVs increased the secretion of interleukin 6, which activated the STAT3 pathway in CRC cells. Furthermore, the conditioned medium of M2-like TAMs promoted cell motility, epithelial-mesenchymal transition, and cell proliferation. However, MVs from CD133-knockdown cells had little effect on TAM polarization and CRC progression. These results demonstrate that CD133-containing MVs induce M2-like TAM polarization and contribute to cancer progression by mediating crosstalk between tumor cells and TAMs in the TME of CRC.

Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data.

BACKGROUND AND PURPOSE: 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. METHODS: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. RESULTS: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. CONCLUSIONS: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

Preparation of Flexible Calcium Carbonate by In Situ Carbonation of the Chitin Fibrils and Its Use for Producing High Loaded Paper.

Flexible calcium carbonate (FCC) was developed as a functional papermaking filler for high loaded paper, which was a fiber-like shaped calcium carbonate produced from the in situ carbonation process on the cellulose micro-or nanofibril surface. Chitin is the second most abundant renewable material after cellulose. In this study, a chitin microfibril was utilized as the fibril core for making the FCC. Cellulose fibrils for the preparation of FCC were obtained by fibrillation of the TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical) treated wood fibers. The chitin fibril was obtained from the ß-chitin from the born of squid fibrillated in water by grinding. Both fibrils were mixed with calcium oxide and underwent a carbonation process by the addition of carbon dioxide, thus the calcium carbonate attached on the fibrils to make FCC. When used in papermaking, both the FCC from chitin and cellulose gave a much higher bulk and tensile strength simultaneously than the conventional papermaking filler of ground calcium carbonate, while maintaining the other essential properties of paper. The FCC from chitin caused an even higher bulk and higher tensile strength than those of the FCC from cellulose in paper materials. Furthermore, the simple preparation method of the chitin FCC in comparison with the cellulose FCC may enable a reduction in the use of wood fibers, process energy, and the production cost of paper materials.

Dietary supplementation with nicotinamide riboside improves fetal growth under hypoglycemia.

Nicotinamide riboside (NR) is considered a super-supplement that prevents obesity and diabetes. While NR has been investigated for various effects depending on nutritional conditions, metabolic research on women and pregnant women has rarely been discussed. In this study, we focused on the glycemic control of NR in females and found the protective role of NR in pregnant animals under hypoglycemic conditions. Metabolic-tolerance tests were performed in vivo under progesterone (P4) exposure after ovariectomy (OVX). NR enhanced resistance to energy deprivation and showed a slight increase in gluconeogenesis in naïve control mice. However, NR reduced hyperglycemia and significantly induced gluconeogenesis in OVX mice. While NR reduced hyperglycemia in the P4-treated OVX mice, it reduced insulin response and substantially increased gluconeogenesis. Similar to animal experiments, NR increased gluconeogenesis and mitochondrial respiration in Hep3B cells. The gluconeogenic function of NR is mediated by tricarboxylic acid cycle (TCA) cycle enrichment, as residual pyruvate could induce gluconeogenesis. NR recovered fetal growth by increasing blood glucose levels when hypoglycemia was induced by diet-restriction during pregnancy. Our study revealed the glucose-metabolic function of NR in hypoglycemic pregnant animals, suggesting NR as a dietary supplement to improve fetal growth. Because diabetic women suffer from hypoglycemia due to insulin therapy, NR has therapeutic potential for use as a glycemic control pill.

Association of Changes in Smoking Intensity With Risk of Dementia in Korea.

Importance: Several observational studies have reported that smoking cessation is associated with a lower risk of dementia. However, no studies have examined the association between change in smoking intensity and risk of dementia. Objective: To investigate the association between a change in smoking intensity, including smoking reduction and smoking cessation, and risk of all dementia. Design, Setting, and Participants: This cohort study used data from the National Health Insurance Service database of Korea. The cohort included participants 40 years or older who underwent biennial health examinations (2009 and 2011) and had current smoking status at the first health examination. The cohort was followed up until December 31, 2018, and statistical analysis was performed between July and December 2021. Exposures: Change in smoking intensity from baseline was defined operationally as follows: quitters (stopped smoking), reducers I (decreased number of cigarettes smoked per day by ≥50%), reducers II (decreased number of cigarettes smoked per day by 20%-50%), sustainers (maintained [decreased or increased] number of cigarettes smoked per day by less than 20%), or increasers (increased number of cigarettes smoked per day by ≥20%). Main Outcomes and Measures: The primary outcome was newly diagnosed dementia, which was identified by prescribed antidementia medications with concomitant International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for dementia. Adjusted hazard ratios and 95% CIs were used to determine the association between change in smoking intensity and incidence of dementia, including Alzheimer disease (AD) and vascular dementia (VaD). Results: A total of 789 532 participants (756 469 males [95.8%]; mean [SD] age, 52.2 [8.5] years) were included. During a median (IQR) follow-up period of 6.3 (6.1-6.6) years, 11 912 dementia events, including 8800 AD and 1889 VaD events, were identified. Overall, participants in the quitter group had a significantly lower risk of all dementia (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.87-0.97) compared with those in the sustainer group. Those in the reducer I (aHR, 1.25; 95% CI, 1.18-1.33) and increaser (aHR, 1.12; 95% CI, 1.06-1.18) groups had a significantly higher risk of all dementia compared with those in the sustainer group.The patterns for AD and VaD remained consistent with patterns for all dementia. Conclusions and Relevance: The results of this study showed that smoking cessation was associated with a lower risk of dementia compared with sustained smoking intensity, while smoking reduction was associated with a higher risk. Smoking cessation should be emphasized in efforts to reduce the disease burden of dementia.

MicroRNA super-resolution imaging in blood for Alzheimer's disease.

We propose a novel blood biomarker detection method that uses miRNA super-resolution imaging to enable the early diagnosis of Alzheimer's disease (AD). Here, we report a singlemolecule detection method for visualizing disease-specific miRNA in tissue from an AD mice model, and peripheral blood mononuclear cells (PBMCs) from AD patients. Using optimized Magnified Analysis of Proteome (MAPs), we confirmed that five miRNAs contribute to neurodegenerative disease in the brain hippocampi of 5XFAD and wild-type mice. We also assessed PBMCs isolated from the whole blood of AD patients and a healthy control group, and subsequently analyzed those samples using miRNA super-resolution imaging. We detected more miR-200a-3p expression in the cornu ammonis 1 and dentate gyrus regions of 3 month-old 5XFAD mice than in wild-type mice. Additionally, miRNA super-resolution imaging of blood provides AD diagnosis platform for studying miRNA regulation inside cells at the single molecule level. Our results present a potential liquid biopsy method that could improve the diagnosis of early stage AD and other diseases. [BMB Reports 2023; 56(3): 190-195].

Reproductive and developmental toxicity screening of bisphenol F by oral gavage in rats.

Bisphenol F (BPF, 4,4'-methylenediphenol) has recently been selected as an alternative to bisphenol A (BPA), which is used in the manufacturing of polycarbonates and epoxy resins. This study aimed to investigate the general, and reproductive/developmental effects of BPF. Therefore, BPF at dose levels of 0, 1, 5, 20, and 100 mg/kg/day was administered daily by oral gavage to Sprague-Dawley rats during the pre-mating, mating, gestation, and early lactation periods, and reproductive and developmental toxicities including general systemic toxicities were investigated. A decrease in body weight and food consumption was observed in the female rats treated with BPF at 20 and 100 mg/kg/day during the pre-mating and gestation periods. Additionally, gamma glutamyl transpeptidase levels were increased in the female rats administered 100 mg/kg/day. At 100 mg/kg/day, ovarian weight decreased and vaginal mucification increased according to a necropsy and histopathological examination, respectively. Moreover, the number of implantation sites and litter size decreased at 100 mg/kg/day. However, no significant BPF-related changes were observed in the male rats. Based on the results of this study, the no-observed-adverse-effect levels (NOAELs) of BPF for general systemic and reproductive effects were 5 and 20 mg/kg/day, respectively.

Effect of Calendering on the Properties of Paper Containing Flexible Calcium Carbonate with a Cellulose Nanofibril Core.

Flexible calcium carbonate (FCC) was prepared by attaching a large amount of calcium carbonate to cellulose nanofibrils (CNFs) by an in situ calcium carbonate formation method. FCC normally consists of CNFs and calcium carbonate at a 1:40 ratio by weight. FCC-containing papers resulted in a higher bulk, higher stiffness, and higher tensile strength than a commercialized ground calcium carbonate (GCC)-containing papers at the same ash content. However, there were speculations that calendering on FCC-containing paper might cause a large drop in bulk and no increase in smoothness due to the larger size of the FCC (avg. dia. 20-30 µm) than the GCC (dia. 2 µm). FCC-containing paper was shown to respond to the calendering process very effectively to increase the Bekk smoothness and to maintain high bulk. Furthermore, FCC-containing paper was so effective in increasing smoothness that it might need less calendering pressure to match the smoothness of GCC-containing paper. If so, there could be potential to increase the bulk and stiffness further in FCC-containing papers at the same smoothness as GCC-containing paper by applying reduced calendering pressure.

Disk-shaped cellulose fibers from red algae, Eucheuma cottonii and its use for high oxygen barrier.

We could prepare disk-shaped fibers without particular mechanical treatments from Eucheuma cottonii, the commonly used red algae for obtaining carrageenan. After carrageenan extraction from cottonii, the residues were bleached using chlorine dioxide and hydrogen peroxide. The morphology of the bleached fiber was disk-shaped one with a very thin fiber wall thickness of less than 100 nm and a diameter of approximately 100 µm. The sugar analysis and X-ray diffraction of the bleached fibers showed that they consisted of mostly glucose and had the same pattern as cellulose I with more than 50% crystalline structure, respectively. Compared to one-dimensional cellulose micro- or nanofibrils, which exhibits slow drainage and possess intolerably high drying energy, these two-dimensional disk-shaped fibers, when formed a layer in water medium, exhibit fast drainage and low drying energy. The formed sheet resulted in excellent transparency and high oxygen barrier property. Therefore, by using these disk-shaped, thin fibers from cottonii, we expect that the biodegradable and transparent oxygen barrier layer can be produced at a paper machine, which is, if possible, extremely difficult in the case of cellulose micro- or nanofibrils due to their slow drainage and high drying energy.

Bis-diamine administration during pregnancy induces developmental and reproductive toxicities in rats.

BACKGROUND: Bis-diamine was developed as amebicidal and male contraceptive agents; however, it is also reported to induce characteristic congenital heart defects especially in the cardiac conotruncal area of rats. Because of its characteristic congenital heart defects, bis-diamine-induced animal models can be used for studying congenital heart defects. However, comprehensive toxicological information regarding bis-diamine-induced congenital heart defects in this animal model is not available. METHODS: In this study, we investigated and characterized an animal model for bis-diamine-induced congenital heart defects. A single dose of 200-mg bis-diamine was administered by oral gavage to pregnant rats on gestation day 10, and then observed the representative toxicological endpoints for general systemic health of pregnant rats, embryo-fetal development, and parturition. RESULTS: Characteristic congenital heart defects and other birth defects similar to DiGeorge syndrome were observed in bis-diamine-administered pregnant rats. In addition, developmental and reproductive toxicity findings, including increased postimplantation loss, decreased fetal weight, increased perinatal death, and increased gestation period, were observed in bis-diamine-administered pregnant rats. In particular, these developmental and reproductive toxicities were observed without maternal toxicity findings. CONCLUSION: These results will be useful to use this animal model for further studies in congenital heart defects, cardiovascular defects, and understanding their mechanisms.

Prenatal developmental toxicity study of 2,4-dichlorobenzyl alcohol in rats.

Sore throat lozenges, which are over-the-counter drugs, contain 2,4-dichlorobenzyl alcohol (DCBA) as the primary ingredient. However, comprehensive data on the prenatal developmental toxicity of DCBA is limited. Therefore, this study was conducted to determine the effects of DCBA on pregnant rats and prenatal development. Sprague-Dawley rats were administered different doses of DCBA (0, 25, 100, 400, and 800 mg/kg/day) daily via an oral gavage from gestation day (GD) 6-19. Thereafter, all the live dams were sacrificed on GD 20, and caesarean sections were conducted. Live fetuses and their placenta were weighed and then examined for external, visceral, and skeletal malformations and variations. Based on the results obtained, dams at 800 mg/kg/day showed systemic toxicities, including a decrease in body weight and food consumption, and liver changes. Additionally, this treatment induced decreases in fetal and placental weights, as well as the increased incidence of retarded ossifications and full supernumery rib, and the decreased number of ossification centers. Therefore, based on these findings, the no-observed-adverse-effect level of DCBA was determined to be 400 mg/kg/day for dams and prenatal development.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IIb Clinical Study to Evaluate the Safety and Efficacy of DHP1401 in Patients with Mild to Moderate Alzheimer's Disease Treated with Donepezil: DHP1401 Randomized Trial in Mild to Moderate Alzheimer's Disease (DRAMA).

BACKGROUND: Preclinical studies in transgenic models of Alzheimer's disease (AD) suggest that DHP1401 has neuroprotective and memory-enhancing effects. OBJECTIVE: To evaluate the efficacy and safety of DHP1401 in AD patients treated with donepezilMethods:Methods: In a double-blind study, patients with mild-to-moderate AD were randomized (1:1:1) to receive a twice daily total dose of 500 mg or 1000 mg DHP1401 or placebo for 24 weeks. Tolerability and safety were monitored at baseline and weeks 12 and 24. RESULTS: total of 180 patients were randomized to Active 1 (500 mg: n = 62), Active 2 (1000 mg: n = 53), and control groups (n = 65) in 16 sites in Korea. There was no significant difference in the Alzheimer's Disease Assessment Scale (ADAS-cog) score, the primary efficacy endpoint, from baseline. However, in the subgroup with mild AD patients (MMSE, 20-26) who received the high dose of DHP1401 and the group that received donepezil 5 mg, the ADAS-cog scores improved. MMSE and K-TMT-e type B were significant in both active groups at week 24. The most frequently observed symptom was dizziness (2.78%), and the most commonly observed reactions were related to metabolism and nutrition disorders (5.00%). No remarkable adverse events were observed for 24 weeks. CONCLUSION: Although the effectiveness of DHP1401 was not proved to be superior as the primary efficacy endpoint, the secondary endpoints, MMSE and K-TMT-e type B, showed significant beneficial effects. Also, the subgroups showed that ADAS-cog scores significantly were improved. DHP1401 could be proven beneficial for the AD treatment by further clinical trials.

Adverse postnatal developmental effects in offspring from humidifier disinfectant biocide inhaled pregnant rats.

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-P), one of the primary biocides used in humidifier disinfectants, caused a fatal pulmonary disease in Korea. Pregnant women were also exposed to PHMG-P, and subsequent studies showed that PHMG-P inhalation during pregnancy adversely affects their health and embryo-fetal development. However, the postnatal developmental effects after birth on prenatally PHMG-P-exposed offspring have not yet been investigated. Therefore, in this study, we aimed to examine the postnatal development of prenatally PHMG-P-exposed offspring. Pregnant rats (22 or 24 females per group) were exposed to PHMG-P during pregnancy in a whole-body inhalation chamber at the target concentrations of 0, 0.14, 1.60, and 3.20 mg/m3. After parturition, the prenatally exposed offspring were transferred to non-exposed surrogate mothers to minimize the secondary effects of severe maternal toxicities. Postnatal development of offspring was then examined with a modified extended one-generation reproductive toxicity study design. At 3.20 mg/m3 PHMG-P, increased perinatal death rates and decreased viability index (postnatal survival of offspring between birth and postnatal day 4) were observed. In addition, F1 offspring had lower body weight at birth that persisted throughout the study. PHMG-P-exposed pregnant rats also had severe systemic toxicities and increased gestation period. At 1.60 mg/m3 PHMG-P, a decreased viability index was also observed with systemic toxicities of PHMG-P-exposed pregnant rats. These results indicate that prenatal PHMG-P exposure adversely affects the offspring's future health and could be used for human risk assessment.

Digital trail making test-black and white: Normal vs MCI.

OBJECTIVE: Trail Making Test-Black and White (TMT-B&W) was developed to assess the cognition of patients with mild cognitive impairment (MCI), dementia, and Alzheimer's disease. Collection and analysis of test results have been limited due to scoring time and efforts required from both administrators and patients during and after taking the test. To increase efficiency and reducing scoring time, a computer version touchscreen-based digital trail making test-black and white (dTMT-B&W) was developed on Android and it was administered on MCI versus cognitively normal controls (NC) participants. The current study examines the sensitivity of newly developed computer version dTMT-B&W on NC and MCI subjects. METHOD: dTMT-B&W was developed using MIT app inventor software, a web-based integrated development environment (IDE) with the Android development tools that are used to build fully functional applications for smartphones and tablets. A total of 44 participants were included, comprised of 22 NC and 22 MCI. The dTMT-TMT-B&W was administered to all NC and MCI subjects. RESULT: dTMT-B&W was designed to be as consistent with the pen-paper TMT-B&W (ppTMT-B&W) where the application is a standalone installation. dTMT-B&W is divided into two parts (Part-A and Part-B), in which the subject attempts to connect black and white numbered circles sequentially as quickly as possible, while still maintaining accuracy. Similarly, the paper-based TMT-B&W requires the subject to connect black and white numbered circles in ascending order, except on a sheet of paper rather than a tablet. dTMT-B&W successfully distinguished NC from MCI subjects. CONCLUSION: dTMT-B&W is an Android application that was successfully developed to be as consistent as possible with the original pen-paper TMT-B&W to establish equal concurrent validity, with some improved features embedded into the design and dTMT-B&W revealed a significant correlation with frontal executive function and this can help in early diagnosing subjects with MCI among NC subjects.

Power Spectral Changes of Quantitative EEG in the Subjective Cognitive Decline: Comparison of Community Normal Control Groups.

PURPOSE: The purpose of this study is to compare and analyze the power spectral changes between subjective cognitive decline (SCD) subjects and normal controls (NC) while checking the preclinical stage of AD in the SCD subjects and to use the derived data for biomarker research that can diagnose early-stage AD in the future. METHODS: We recruited 23 SCD patients and 23 normal control subjects and QEEG analysis including power spectral density (PSD) and source-level analysis were performed. An automated preprocessing procedure and statistical analysis were performed by iSync Brain® (iMediSync Inc., Republic of Korea) (https://isyncbrain.com/) using the international standard 10-20 system (19 electrodes). RESULTS: Absolute PSD, there was no statistically significant difference in all of the EEG power measurements of the 19 channels. In the relative PSD analysis, the average delta band power of the SCD group was significantly higher in Fp2, F4, and F8 than NC. Alpha1 band power of the O1 channel was 22.56±16.05 for the SCD group and 33.19±19.05 for the NC (p-value <0.05). Source-level analysis did not show a statistically significant difference. CONCLUSION: SCD subjects showed a partial increase of delta waves in the frontal lobe region and a partial decrease in alpha1, a fast wave in the occipital region, compared to the NC. SCD is considered one of the earliest clinical symptoms of AD and it is predicted to be related to minor nerve damage. We were able to observe the power spectral changes in SCD subjects in this cross-sectional study, a large number of subjects and longitudinal studies are needed to evaluate their predictability for future deterioration such as conversion to MCI.

Potential Novel Genes for Late-Onset Alzheimer's Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study.

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.

Use of the Clock Drawing Test and the Rey-Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment.

BACKGROUND: The Clock Drawing Test (CDT) and Rey-Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. METHODS: The CDT and RCFT-copy data were obtained from patients aged 60-80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab. RESEARCH: google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). RESULTS: The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. CONCLUSIONS: The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.