IOS Press Acta Medica Okayama 0926-9630 2025 Assessing the Proportion of Clinical Trial Eligibility Criteria Expressible with Standard EHR Data Elements 1892 1893 EN Risa Okazaki Department of Pharmacy, Okayama University Hospital Kunihisa Kamikawa Center for Innovative Clinical Medicine, Okayama University Hospital Hideki Uno Center for Innovative Clinical Medicine, Okayama University Hospital Hiroto Okuda Division of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University Hospital Shihoko Namba Division of Clinical Research of New Drugs and Therapeutics, Center for Innovative Clinical Medicine, Okayama University Hospital Mitsunobu Kano Graduate School of Interdisciplinary Science and Technology in Health Systems, Okayama University Mizuki Morita Graduate School of Interdisciplinary Science and Technology in Health Systems, Okayama University Patient recruitment for clinical trials often requires substantial human effort and experiences delays, leading to increased drug development costs. Leveraging electronic health records (EHRs) may improve the accuracy of estimates of potentially recruitable patients. We evaluated the feasibility of using EHRs by analyzing the proportion of computable eligibility criteria. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 0926-9630 2025 Trend of Digital Biomarkers (dBM) as Endpoints in Clinical Trials: Secondary Analysis of Open Data 391 395 EN Mizuki Morita Department of Biomedical Informatics, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mina Honjoh Faculty of Health Sciences, Okayama University Medical School Takahiro Yamane Department of Biomedical Informatics, Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University This study examined clinical trial trends to guide digital biomarker (dBM) guideline development. Analysis of 2005–2023 data was conducted to assess the frequency and types of dBM used as endpoints (dEP) in these trials and the associated target diseases. Clinical trials using dEP increased from 0–7 per year (2005–2019) to 15–20 annually from 2020. Endocrine and metabolic conditions were the most common targets, showing a distinct disease distribution compared to overall trials. Most measurements used actigraphy devices or blood glucose sensors, with glucose sensors focusing on metabolic conditions while actigraphy covered broader applications. Additionally, 42.4% of trials used dEP as primary endpoints. While dEP use is growing, it remains limited in disease scope and device variety. Expanding both would enhance their utility in clinical research. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 100 1 2024 A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease by Selected Reaction Monitoring 219 228 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minaki Hamada Protosera, Inc. Kyoichi Asada Protosera, Inc. Lyang-Ja Lee Protosera, Inc. Hidehisa Tachiki Protosera, Inc. Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background:With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. Objective:The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods:We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results:The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions:In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 96 2 2023 Protective Effects of Rivaroxaban on White Matter Integrity and Remyelination in a Mouse Model of Alzheimer’s Disease Combined with Cerebral Hypoperfusion 609 622 EN Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background:Alzheimer’s disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear. Objective:The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice. Methods:In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter. Results:The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss. Conclusions:These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 86 1 2022 Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer’s Disease Mice 111 123 EN Zhihong Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haibo Yu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiao Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xinran Hu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuting Bian Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hongming Sun Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Taijun Yunoki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe National Center Hospital, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 68 4 2019 Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model 1667 1675 EN Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xia Liu Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yong Huang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kota Sato Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mami Takemoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n = 10) group (*p < 0.05 and **p < 0.01 versus WT; #p < 0.05 and # #p < 0.01 versus APP23). The present study provides an upregulation of anti-inflammatory ITIH4 and a downregulation of pro-inflammatory TNFα-dependent AHSG in a novel AD plus HP mice model. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 71 1 2019 Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model 327 339 EN Tian Feng Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jingwei Shang Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Xiaowen Shi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yumiko Nakano Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Tsunoda Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Emi Nomura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryo Sasaki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Namiko Matsumoto Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nozomi Hishikawa Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuyuki Ohta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis. No potential conflict of interest relevant to this article was reported.