研究者詳細 - 田岡　俊昭

論文 - 田岡　俊昭

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Therapeutic switch from plasma to recombinant ADAMTS13 for patients with congenital TTP from Japanese real-world data

Sakai, K; Hamamura, A; Yoshimura, Y; Abe, M; Ogawa, Y; Tanaka, K; Hattori, N; Tokugawa, T; Kanai, R; Ikejiri, F; Takeyama, M; Taoka, T; Fujita, N; Kanaya, M; Koh, K; Shiragami, H; Azumi, H; Saito, K; Matsumoto, M

BLOOD 145 巻 ( 20 ) 頁： 2390 - 2395 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blood

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ damage caused by pathogenic ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) variants. ADAMTS13-containing product, including fresh-frozen plasma (FFP), and plasma-derived factor VIII concentrates are commonly used to supply ADAMTS13; however, frequent hospital visits and allergic reactions are major drawbacks. A recombinant ADAMTS13 (rADAMTS13) was recently developed to address these issues. However, real-world evidence has not been reported owing to the rarity of this condition. This study compared the efficacy and safety of FFP and rADAMTS13 in 14 Japanese patients, including 5 patients with end-stage renal disease who were excluded from the phase 3 trial. The median peak level of ADAMTS13 activity 15 minutes after rADAMTS13 administration was significantly higher than that after FFP (68.4% vs 15.9%; P < .001). ADAMTS13 activity 1 week after rADAMTS13 administration was well maintained compared with FFP infusion (11.6% vs 5.1%; P < .001). Patients reported no allergic reactions after rADAMTS13 administration and appreciated the convenience of a single infusion of rADAMTS13, suggesting that rADAMTS13 is a safe and effective alternative to FFP in patients with cTTP. To our knowledge, this is the first publication of patients with cTTP who switched FFP to novel rADAMTS13 from Japanese real-world data.

DOI： 10.1182/blood.2024027516

Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function 国際誌 Open Access

Schirge, PM; Perneczky, R; Taoka, T; Ruiz-Rizzo, AL; Ersoezlue, E; Forbrig, R; Guersel, S; Kurz, C; Brendel, M; Hellmann-Regen, J; Priller, J; Schneider, A; Jessen, F; Düzel, E; Buerger, K; Teipel, S; Laske, C; Peters, O; Spruth, E; Fliessbach, K; Rostamzadeh, A; Glanz, W; Janowitz, D; Kilimann, I; Sodenkamp, S; Ewers, M; Rauchmann, BS

ALZHEIMERS RESEARCH & THERAPY 17 巻 ( 1 ) 頁： 62 - 62 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Alzheimer S Research and Therapy

Background: Alzheimer’s disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD. This study aimed to investigate alterations in the function of the glymphatic system in individuals with AD versus healthy controls (HC), and to explore its association with Aβ, cerebrovascular disease (CVD), white matter hyperintensities (WMH), and cognitive function. Methods: DTI MRI data from three independent study cohorts (ActiGliA: AD n = 16, Controls n = 18; DELCODE: AD n = 54, Controls n = 67; ADNI: AD n = 43, Controls n = 49) were used to evaluate the perivascular space (PVS) integrity; a potential biomarker for glymphatic activity. The DTI-Along the Perivascular Space technique was used to measure water diffusion along PVS providing an index to assess the efficiency of the glymphatic system’s waste clearance function. WMH load was quantified in FLAIR MRI using the lesion segmentation tool. We quantified WMHs volume within our defined region of interest (ROI) and excluded participants with any WMHs to avoid confounding the ALPS-Index. Associations with cerebrospinal fluid (CSF) AD hallmark biomarkers, cognitive performance (MMSE) and clinical severity (CDR) were assessed. Results: AD patients had a significantly lower ALPS-Index vs. healthy controls (ActiGliA: AD: mean = 1.22, SD = 0.12; Controls: mean = 1.36, SD = 0.14, p = 0.004; DELCODE: AD: mean = 1.26, SD = 0.18; Controls: mean = 1.34, SD = 0.2, p = 0.035; ADNI: AD: mean = 1.08, SD = 0.24; Controls: mean = 1.19, SD = 0.13, p = 0.008). The ALPS-Index was associated with CSF Aβ concentration, WMH number and MMSE and CDR. WMH, found in the ROIs correlated negatively with the ALPS-Index. Conclusions: This study highlights the potential of the DTI-ALPS-Index as a biomarker for glymphatic dysfunction in AD. It underscores the importance of considering vascular factors and the glymphatic system in the pathogenesis and diagnosis of AD as WMHs in the ROI could cause disturbances and inaccurate indices.

DOI： 10.1186/s13195-025-01707-9

Assessing large language models for Lugano classification of malignant lymphoma in Japanese FDG-PET reports 国際誌 Open Access

Ito, R; Kato, K; Nanataki, K; Abe, Y; Ogawa, H; Minamimoto, R; Kato, K; Taoka, T; Naganawa, S

EJNMMI REPORTS 9 巻 ( 1 ) 頁： 8 - 8 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Ejnmmi Reports

Purpose: This study evaluates the performance of four large language models (LLMs) in classifying malignant lymphoma stages using the Lugano classification from free-text FDG-PET reports in Japanese Specifically, we assess GPT-4o, Claude 3.5 Sonnet, Llama 3 70B, and Gemma 2 27B in their ability interpret unstructured radiology texts. Materials and methods: In a retrospective single-center study, 80 patients who underwent staging FDG-PET/CT for malignant lymphoma were included. The “Findings” sections of their reports were analyzed without pre-processing. Each LLM assigned Lugano stages based on these reports. Performance was compared to reference standard stages determined by expert radiologists. Statistical analyses involved overall accuracy, weighted kappa for agreement. Results: GPT-4o achieved the highest accuracy at 75% (60/80 cases) with substantial agreement (weighted kappa κ = 0.801). Claude 3.5 Sonnet had 61.3% accuracy (49/80, κ = 0.763). Gemma 2 27B and Llama 3 70B showed accuracies of 58.8% and 57.5%, respectively, all indicating substantial agreement. Conclusion: GPT-4o outperformed other LLMs in assigning Lugano classification from Japanese FDG-PET free-text reports. This demonstrated the potential of advanced LLMs to interpret clinical texts. While the immediate clinical utility of automatically predicting a Lugano stage from an existing report may be limited, these results highlight the value of LLMs for understanding and standardizing free-text radiology data.

DOI： 10.1186/s41824-025-00246-8

Effects of Sleep-Disordered Breathing on Daytime Brain Activity in Community-Dwelling Older Adults 国際誌 Open Access

Shibata, H; Noda, A; Mao, YJ; Iwamoto, K; Okuda, M; Okada, I; Miyata, S; Taoka, T; Yasuma, F

SLEEP SCIENCE 18 巻 ( 01 ) 頁： e10 - e16 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Sleep Science

Introduction Sleep-disordered breathing (SDB) is associated with an increased risk of cardiovascular diseases. The present study aimed to examine the influence of SDB on daytime brain activity in the community-dwelling older adults. Material and Methods Eighty one consecutive volunteers aged 60 years or older (mean age 70.5 ± 4.8 years) participated in the present study. Daytime brain activity was assessed by measuring the peak cortical oxygenated hemoglobin (OxyHb) levels and area under the near-infrared spectroscopy (NIRS) curve. The respiratory event index (REI) and 3% oxygen desaturation index (3%ODI) were evaluated using a home sleep-apnea test. Results The peak OxyHb and area under the NIRS curve were significantly lower in the participants with REI ≥ 15/h than those with REI < 15/h. The body mass index (BMI), REI, 3%ODI, and Epworth sleepiness scale (ESS) scores were significantly correlated with peak OxyHb levels (BMI: r = -0.202, p = 0.035; REI: r = -0.307, p = 0.003; 3%ODI: r = -0.321, p = 0.002; and ESS score: r = -0.287, p = 0.005). Also, the BMI, REI, and 3%ODI were significantly correlated with the area under the NIRS curve (BMI: r = -0.306, p = 0.002; REI: r = -0.326, p = 0.002; and 3%ODI: r =-0.322, p = 0.002), and BMI was a significant factor associated with the area under the NIRS curve. Conclusions Brain activity during wakefulness was associated with severities of SDB and obesity. A simple NIRS may yield unique information for characterizing the decline in daytime brain activity of the community-dwelling older adults.

DOI： 10.1055/s-0044-1782627

Imaging of Movement Disorders

Toshiaki Taoka

Medical Radiology 2025年2月

Direct Visualization of Tracer Permeation into the Endolymph in Human Patients Using MR Imaging Open Access

Naganawa, S; Ito, R; Kawamura, M; Taoka, T; Yoshida, T; Sone, M

MAGNETIC RESONANCE IN MEDICAL SCIENCES 24 巻 ( 2 ) 頁： 253 - 261 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Magnetic Resonance in Medical Sciences

Purpose: The endolymph of the inner ear, vital for balance and hearing, has long been considered impermeable to intravenously administered gadolinium-based contrast agents (GBCAs) due to the tight blood-endolymph barrier. However, anecdotal observations suggested potential GBCA entry in delayed heavily T2-weighted 3D-real inversion recovery (IR) MRI scans. This study systematically investigated GBCA distribution in the endolymph using this 3D-real IR sequence. Methods: Forty-one patients suspected of endolymphatic hydrops (EHs) underwent pre-contrast, 4-h, and 24-h post-contrast 3D-real IR imaging. Signal intensity in cerebrospinal fluid (CSF), perilymph, and endolymph was measured and analyzed for temporal dynamics of GBCA uptake, correlations between compartments, and the influence of age and presence of EH. Results: Endolymph showed a delayed peak GBCA uptake at 24h, contrasting with peaks in perilymph and CSF at 4h. Weak to moderate positive correlations between endolymph and CSF contrast effect were observed at both 4 (r = 0.483) and 24h (r = 0.585), suggesting possible inter-compartmental interac-tions. Neither the presence of EH nor age significantly influenced endolymph enhancement. However, both perilymph and CSF contrast effects significantly correlated with age at both time points. Conclusion: This study provides the first in vivo systematic confirmation of GBCA entering the endo-lymph following intravenous administration. Notably, endolymph uptake peaked at 24h, significantly later than perilymph and CSF. The lack of a link between endolymph contrast and both perilymph and age suggests distinct uptake mechanisms. These findings shed light on inner ear fluid dynamics and their potential implications in Ménière’s disease and other inner ear disorders.

DOI： 10.2463/mrms.mp.2024-0011

The Endolymph Signal in Non-contrast Enhanced 3D-real IR Image Differs between the Ears with and without Significant Endolymphatic Hydrops Open Access

Naganawa, S; Ito, R; Kawamura, M; Taoka, T; Yoshida, T; Sone, M

MAGNETIC RESONANCE IN MEDICAL SCIENCES 24 巻 ( 4 ) 頁： n/a 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Magnetic Resonance in Medical Sciences

Purpose: To investigate whether significant differences exist in labyrinthine lymph fluid signal intensities on non-contrast-enhanced 3D real inversion recovery (3D-real IR) images between patients with and without significant endolymphatic hydrops (EH), potentially enabling the non-contrast detection of EH. Methods: Thirty-nine patients suspected of having EH underwent 3D-real IR MRI before and 4 hours after intravenous administration of a single dose of gadobutrol. Signal intensities of the cerebrospinal fluid (CSF), perilymph, and endolymph were manually measured on pre-contrast images using ROIs. Patients were categorized into 2 groups based on post-contrast imaging: those with significant EH and those without. Normalized signal intensities (nSIs) of the endolymph were calculated and compared between the groups using the Mann–Whitney U test. Results: The nSIs of the vestibular endolymph on non-contrast 3D-real IR images were significantly lower in the group with significant EH compared to the group without EH (P < 0.05), suggesting T1 prolongation in the vestibular endolymph of patients with significant EH. However, considerable overlap was observed in the nSIs between the 2 groups, and significant EH did not always result in T1 prolongation. No significant differences were found in the nSIs of the perilymph or CSF between the groups. Conclusion: The study suggests that T1 prolongation occurs in the vestibular endolymph in cases of significant EH. This finding indicates the potential for developing non-contrast MRI methods to detect EH and underscores the importance of understanding the mechanisms behind T1 changes in the endolymph. Further research with larger patient cohorts and inclusion of healthy control subjects is necessary to validate these results and to elucidate the pathophysiology of EH in Ménière’s disease.

DOI： 10.2463/mrms.mp.2024-0191

Registry-Based Assessment of Shunt Operation Methods and Outcomes in Idiopathic Normal Pressure Hydrocephalus (RASHOMON Study): Protocol for a Multicenter Prospective Observational Cohort Study Open Access

Okumura, E; Takeuchi, K; Momota, H; Nagatani, T; Taoka, T; Aimi, Y; Hashizume, A; Okazaki, M; Saito, R

JMIR RESEARCH PROTOCOLS 14 巻頁： e80678 2025年

Preliminary Findings on Non-contrast Enhanced Positive Endolymph Images: Limited Delineation of Endolymphatic Space Open Access

Naganawa, S; Ito, R; Kawamura, M; Taoka, T; Yoshida, T; Sone, M

MAGNETIC RESONANCE IN MEDICAL SCIENCES 24 巻 ( 4 ) 頁： n/a 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Magnetic Resonance in Medical Sciences

A recently proposed non-contrast MRI technique for evaluating endolymphatic hydrops employs inversion recovery without T2-preparation and the subtraction of 2 inversion time images. However, our high-resolution non-contrast positive endolymph images (PEI) reveal inconsistencies in delineating the endolymphatic space, challenging this method’s reliability. Comprehensive analysis is required to address the interplay among signal intensity, T1 relaxation times, and inversion efficiency within endolymphatic and perilymphatic spaces to establish its diagnostic accuracy.

DOI： 10.2463/mrms.bc.2025-0005

Correction to: Polygenic effects on the risk of Alzheimer’s disease in the Japanese population (Alzheimer's Research & Therapy, (2024), 16, 1, (45), 10.1186/s13195-024-01414-x) Open Access

Kikuchi M., Miyashita A., Hara N., Kasuga K., Saito Y., Murayama S., Kakita A., Akatsu H., Ozaki K., Niida S., Kuwano R., Iwatsubo T., Nakaya A., Ikeuchi T., Weiner M.W., Mason S.S., Albers C.S., Knopman D., Johnson K., Aisen P., Petersen R., Jack C.R., Jagust W., Trojanowki J.Q., Toga A.W., Schneider L.S., Pawluczyk S., Beccera M., Teodoro L., Spann B.M., Beckett L., Green R.C., Morris J., Shaw L.M., Ances B., Morris J.C., Carroll M., Creech M.L., Franklin E., Mintun M.A., Schneider S., Oliver A., Kaye J., Quinn J., Silbert L., Lind B., Carter R., Dolen S., Brewer J., Vanderswag H., Fleisher A., Heidebrink J.L., Lord J.L., Doody R.S., Villanueva-Meyer J., Chowdhury M., Rountree S., Dang M., Stern Y., Honig L.S., Bell K.L., Marson D., Griffith R., Clark D., Geldmacher D., Brockington J., Roberson E., Love M.N., Grossman H., Mitsis E., Shah R.C., deToledo-Morrell L., Duara R., Varon D., Greig M.T., Roberts P., Albert M., Onyike C., D’Agostino D., Kielb S., Galvin J.E., Cerbone B., Michel C.A., Pogorelec D.M., Rusinek H., de Leon M.J., Glodzik L., De Santi S., Doraiswamy P.M., Petrella J.R., Borges-Neto S., Wong T.Z., Coleman E., Smith C.D., Jicha G., Hardy P., Sinha P., Oates E., Conrad G., Porsteinsson A.P.

Alzheimer S Research and Therapy 16 巻 ( 1 ) 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Alzheimer S Research and Therapy

Following publication of the original article [1], the authors corrected an error in Fig. 2. (Figure presented.) The PRS.noAPOE and PRS.adjLD correlated with CSF Tau/Aβ42 ratios in the MCI. CSF tTau/Aβ42 (A, C) and pTau/Aβ42 (B, D) ratios by decile of PRS are shown in each diagnostic group. The participants were divided into ten groups based on the PRS.noAPOE, ranging from the lowest group (1st decile) to the highest group (10th decile). CN = cognitively normal; MCI = mild cognitive impairment; ADD = Alzheimer’s disease dementia Error: Figs. 2C and D are the same figures as Figs. 2A and B in the published article. The corrected figure is given below: The original article [1] has been updated.

DOI： 10.1186/s13195-024-01514-8

Decreased Water Diffusivity Along the Perivascular Space in Older Adults With Poor Sleep Quality 国際誌

Kikuta, J; Kamagata, K; Takabayashi, K; Hayakawa, Y; Taoka, T; Saito, Y; Uchida, W; Guo, S; Yoshida, S; Yamazaki, K; Wada, A; Kaga, H; Tamura, Y; Kawamori, R; Watada, H; Aoki, S

JOURNAL OF NEUROSCIENCE RESEARCH 102 巻 ( 12 ) 頁： e70005 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Neuroscience Research

This study included 52 Japanese older adults with Pittsburgh Sleep Quality Index (PSQI) scores > 5 and 52 healthy controls (HCs) with PSQI score ≤ 5. Diffusion-weighted imaging (DWI) and 3D T1-weighted imaging were acquired using 3T magnetic resonance imaging. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated using preprocessed DWI. The choroid plexus volume (CPV) was calculated using FreeSurfer 6.0. The mean ALPS index and CPV were compared between the older adults with poor sleep quality (PSQ) and HCs using a general linear model, adjusted for covariates including age, sex, years of education, total intracranial volume, systolic blood pressure, hemoglobin A1c, and white matter lesion volume. We also conducted a partial correlation analysis between the mean ALPS index and CPV, Montreal Cognitive Assessment (MoCA), and PSQI scores, adjusting for all the mentioned covariates. The PSQ group had a significantly lower mean ALPS index than HCs. The mean ALPS index in the PSQ group was negatively correlated with CPV and positively correlated with the MoCA score. Therefore, older adults with PSQ may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins. This impairment may be associated with an increase in CPV and cognitive dysfunction.

DOI： 10.1002/jnr.70005

Decreased diffusivity along the perivascular space and cerebral hemodynamic disturbance in adult moyamoya disease 国際誌 Open Access

Hara, S; Kikuta, J; Takabayashi, K; Kamagata, K; Hayashi, S; Inaji, M; Tanaka, Y; Hori, M; Ishii, K; Nariai, T; Taoka, T; Naganawa, S; Aoki, S; Maehara, T

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 44 巻 ( 10 ) 頁： 1787 - 1800 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Cerebral Blood Flow and Metabolism

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via <sup>15</sup>O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = −0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = −0.60, P = 0.003; and oxygen extraction fraction, ρ = −0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = −0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed.

DOI： 10.1177/0271678X241245492

その他リンク： https://journals.sagepub.com/doi/full-xml/10.1177/0271678X241245492

Imaging evaluation and volumetric measurement of the space surrounding the diploic veins Open Access

Nakamichi, R; Taoka, T; Ito, R; Yoshida, T; Sone, M; Naganawa, S

JAPANESE JOURNAL OF RADIOLOGY 42 巻 ( 9 ) 頁： 953 - 961 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Radiology

Purpose: The diploic veins have been suggested to be involved in the excretion of cerebrospinal fluid and intracranial waste products; however, to date, there have been no reports evaluating the space surrounding the diploic veins. Therefore, we aimed to visualize the distribution of gadolinium-based contrast agent (GBCA) in the space surrounding the diploic veins and to evaluate the spatial characteristics. Materials and methods: Ninety-eight participants (aged 14–84 years) were scanned 4 h after intravenous GBCA injection at Nagoya University Hospital between April 2021 and December 2022. The volume of the space surrounding the diploic veins where the GBCA was distributed was measured using contrast-enhanced T1-weighted images with the application of three-axis motion-sensitized driven equilibrium. The parasagittal dura (PSD) volume adjacent to the superior sagittal sinus was also measured using the same images. Both volumes were corrected for intracranial volume. The correlation between age and the corrected volume was examined using Spearman’s rank correlation coefficient; the relationship between the corrected volume and sex was assessed using the Mann–Whitney U test. Results: A significant weak negative correlation was observed between the volume of the space surrounding the diploic veins and age (r = −0.330, p < 0.001). Furthermore, there was a significant weak positive correlation between the PSD volume and age (r = 0.385, p < 0.001). Both volumes were significantly greater in men than in women. There was no correlation between the volume of the space surrounding the diploic veins and the volume of the PSD. Conclusion: The volume of the space surrounding the diploic veins was measurable and, in contrast to the volume of the PSD, was greater in younger participants. This space may be related to intracranial excretory mechanisms and immune responses during youth, requiring further research.

DOI： 10.1007/s11604-024-01572-w

The Glymphatic System in Humans: Investigations With Magnetic Resonance Imaging 国際誌

Naganawa, S; Taoka, T; Ito, R; Kawamura, M

INVESTIGATIVE RADIOLOGY 59 巻 ( 1 ) 頁： 1 - 12 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Investigative Radiology

The concept of the glymphatic system was proposed more than a decade ago as a mechanism for interstitial fluid flow and waste removal in the central nervous system. The function of the glymphatic system has been shown to be particularly activated during sleep. Dysfunction of the glymphatic system has been implicated in several neurodegenerative diseases. Noninvasive in vivo imaging of the glymphatic system is expected to be useful in elucidating the pathophysiology of these diseases. Currently, magnetic resonance imaging is the most commonly used technique to evaluate the glymphatic system in humans, and a large number of studies have been reported. This review provides a comprehensive overview of investigations of the human glymphatic system function using magnetic resonance imaging. The studies can be divided into 3 categories, including imaging without gadolinium-based contrast agents (GBCAs), imaging with intrathecal administration of GBCAs, and imaging with intravenous administration of GBCAs. The purpose of these studies has been to examine not only the interstitial fluid movement in the brain parenchyma, but also the fluid dynamics in the perivascular and subarachnoid spaces, as well as the parasagittal dura and meningeal lymphatics. Recent research has even extended to include the glymphatic system of the eye and the inner ear. This review serves as an important update and a useful guide for future research directions.

DOI： 10.1097/RLI.0000000000000969

Assessment of cognitive function and sleep-wake rhythms in community-dwelling older adults

Okuda, M; Noda, A; Iwamoto, K; Hishikawa, N; Miyata, S; Yasuma, F; Taoka, T; Ozaki, N; Suhr, JA; Miyazaki, S

SLEEP AND BIOLOGICAL RHYTHMS 22 巻 ( 1 ) 頁： 137 - 145 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Sleep and Biological Rhythms

Disruption of the circadian rhythm and sleep–wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60 years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r = − 0.276, p = 0.013, TE: r = 0.311, p = 0.005, PEN: r = 0.241, p = 0.032, NPE: r = 0.250, p = 0.025, DMS: r = 0.235, p = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD, revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: β = − 0.322, p = 0.004; sleep timing SD: β = − 0.250, p = 0.022). Assessment of sleep–wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population.

DOI： 10.1007/s41105-023-00491-z

Glymphatic System Dysfunction in Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Antibody?Associated Disorders: Association with Clinical Disability 査読有り

Hagiwara, A; Tomizawa, Y; Hoshino, Y; Yokoyama, K; Kamagata, K; Sekine, T; Takabayashi, K; Nakaya, M; Maekawa, T; Akashi, T; Wada, A; Taoka, T; Naganawa, S; Hattori, N; Aoki, S

AMERICAN JOURNAL OF NEURORADIOLOGY 45 巻 ( 1 ) 頁： 66 - 71 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：American Journal of Neuroradiology

BACKGROUND AND PURPOSE: Impaired glymphatic function has been suggested to be implicated in the pathophysiology of MS and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder. This study aimed to investigate the interstitial fluid dynamics in the brain in patients with myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), another demyelinating disorder, using a noninvasive imaging technique called the diffusivity along the perivascular space (ALPS) index. MATERIALS AND METHODS: A prospective study was conducted on 16 patients with MOGAD in remission and 22 age- and sexmatched healthy control subjects. MR imaging was performed using a 3T scanner, and the ALPS index was calculated using diffusion MR imaging data with a b-value of 1000 s/mm2. The ALPS index and gray matter volumes were compared between the 2 groups, and these parameters were correlated with the Expanded Disability Status Scale. RESULTS: The mean ALPS index of patients with MOGAD was significantly lower than that of healthy controls (Cohen d 0.93, false discovery rate-corrected P .02). The lower mean ALPS index was significantly associated with a worse Expanded Disability Status Scale score (Spearman r _0.51; 95% CI, _0.85 to _0.02; P .03). However, cortical volume and deep gray matter volume were not significantly different between the 2 groups, and they were not correlated with the Expanded Disability Status Scale. CONCLUSIONS: This study suggests that patients with MOGAD may have impaired glymphatic function, as measured by the ALPS index, which is associated with patient disability. Further study is warranted with a larger sample size.

DOI： 10.3174/ajnr.A8066

Characteristics of donor vessels and cerebral blood flow in the chronic phase after combined revascularization surgery for moyamoya disease 国際誌

Mamiya, T; Araki, Y; Taoka, T; Fujita, N; Yokoyama, K; Uda, K; Muraoka, S; Kanamori, F; Takayanagi, K; Ishii, K; Nishihori, M; Izumi, T; Kato, K; Saito, R

CLINICAL NEUROLOGY AND NEUROSURGERY 236 巻頁： 108110 - 108110 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Clinical Neurology and Neurosurgery

Objective: This study aimed to analyze whether the development of donor vessels after combined revascularization surgery for moyamoya disease (MMD) is related to cerebral blood flow (CBF) changes. Methods: We retrospectively reviewed the charts of 11 adult (12 hemispheres) and 13 pediatric (19 hemispheres) patients who underwent combined revascularization in our department. The total vessel cross-sectional area (TVA) was the sum of the cross-sectional areas of the superficial temporal, middle meningeal, and deep temporal arteries imaged using time-of-flight magnetic resonance angiography. The ipsilateral relative CBF (RCBF) on the brain surface in the craniotomy area was calculated by single-photon emission computed tomography. ΔTVA and ΔRCBF were defined as the preoperative and postoperative ratios of TVA and RCBF, and their correlations were analyzed in adult and pediatric patients. Results: The TVA and RCBF showed a significant increase after surgery, regardless of the age group. However, there was no significant correlation between ΔTVA and ΔRCBF in either the adult or pediatric groups. While the adult group exhibited significantly higher ΔRCBF values compared to the pediatric group (p < 0.01, r = −0.44), the ΔTVA values were higher in the pediatric group compared to the adult group (p = 0.06). Conclusions: In the chronic phase after combined revascularization surgery for MMD, the development of measurable TVA of donor vessels does not necessarily correlate with an increase in CBF around the craniotomy area.

DOI： 10.1016/j.clineuro.2023.108110

Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space. 査読有り

Tuerxun R, Kamagata K, Saito Y, Andica C, Takabayashi K, Uchida W, Yoshida S, Kikuta J, Tabata H, Naito H, Someya Y, Kaga H, Miyata M, Akashi T, Wada A, Taoka T, Naganawa S, Tamura Y, Watada H, Kawamori R, Aoki S

Frontiers in aging neuroscience 16 巻頁： 1362457 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Aging Neuroscience

Background and purpose: Glymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance. Materials and methods: In our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates. Results: In the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = −1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = −1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = −0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = −0.35, p < 0.005). Conclusion: The ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.

DOI： 10.3389/fnagi.2024.1362457

Assessing the Real-World, Long-Term Impact of Lemborexant on Sleep Quality in a Home-Based Clinical Study.

Miyata S, Iwamoto K, Okada I, Fujimoto A, Kogo Y, Mori D, Amano M, Matsuyama N, Nishida K, Ando M, Taoka T, Naganawa S, Ozaki N

Nature and science of sleep 16 巻頁： 291 - 303 2024年

Glymphatic system impairment in sleep disruption: diffusion tensor image analysis along the perivascular space (DTI-ALPS) 査読有り

Saito, Y; Hayakawa, Y; Kamagata, K; Kikuta, J; Mita, T; Andica, C; Taoka, T; Uchida, W; Takabayashi, K; Tuerxun, R; Mahemuti, Z; Yoshida, S; Kitagawa, T; Arai, T; Suzuki, A; Sato, K; Nishizawa, M; Akashi, T; Shimoji, K; Wada, A; Aoki, S

JAPANESE JOURNAL OF RADIOLOGY 41 巻 ( 12 ) 頁： 1335 - 1343 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Radiology

Purpose: This study aimed to evaluate the relationship between sleep quality as assessed using the Pittsburgh Sleep Quality Index (PSQI) and the index of diffusivity along the perivascular space (ALPS index), a possible indirect indicator of glymphatic system activity. Materials and methods: This study included the diffusion magnetic resonance imaging (MRI) data of 317 people with sleep disruption and 515 healthy controls (HCs) from the Human Connectome Project (WU-MINN HCP 1200). The ALPS index was calculated automatically based on diffusion tensor image analysis (DTI)-ALPS of diffusion MRI. The ALPS index of the sleep disruption and HC groups was compared using general linear model (GLM) analysis with covariates, such as age, sex, level of education, and intracranial volume. In addition, to confirm the relationship between sleep quality and the ALPS index in the sleep disruption group as well as evaluate the effect of each PSQI component on the ALPS index, correlation analyses between the ALPS indices and PSQI scores of all the components and between the ALPS index and each PSQI component was performed using GLM analysis with the abovementioned covariates, respectively. Results: The ALPS index was significantly lower in the sleep disruption group than in the HC group (p = 0.001). Moreover, the ALPS indices showed significant negative correlations with the PSQI scores of all the components (false discovery rate [FDR]-corrected p < 0.001). Two significant negative correlations were also found between the ALPS index and PSQI component 2 (sleep latency, FDR-corrected p < 0.001) and 6 (the use of sleep medication, FDR-corrected p < 0.001). Conclusion: Our findings suggest that glymphatic system impairment contributes to sleep disruption in young adults.

DOI： 10.1007/s11604-023-01463-6

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