Faculty Profiles - TAKEMOTO Mami

Papers - TAKEMOTO Mami

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A unique case with positive anti-myelin oligodendrocyte glycoprotein antibody presenting multiple brain lesions

Namiko Matsumoto, Kota Sato, Nozomi Hishikawa, Yuko Kawahara, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Kentaro Fujii, Kazuhiko Kurozumi, Isao Date, Toshiyuki Takahashi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 92 - 95 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The accurate diagnosis of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases is sometimes challenging due to its various central nervous system (CNS) lesions. Here, we report a 22-year-old man with positive anti-MOG antibody presenting multiple brain lesions including a brainstem tumefactive demyelinating lesion (TDL), cortical edematous lesions, and a periventricular white matter lesion. These variety of lesions made the diagnosis challenging, especially because TDL is quite rare among MOG antibody-associated disease patients. The present case suggests the importance to check anti-MOG antibody for patients presenting atypical multiple CNS lesions.

DOI： 10.1111/ncn3.12364

Different clinical and neuroimaging features of Japanese dementia siblings with a new N-terminal mutation (Val225Ala) of APP gene

Yasuyuki Ohta, Nozomi Hishikawa, Ken Ikegami, Kota Sato, Yosuke Osakada, Mami Takemoto, Toru Yamashita, Yoshio Omote, Takeshi Ikeuchi, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 72 482 - 484 2020.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Autosomal dominant amyloid precursor protein (APP) mutations in familial Alzheimer's disease accelerate the amyloid beta (A beta) pathology. Here we describe Japanese siblings with a new N-terminal mutation (a heterogeneous c.674T>C, p.Val225Ala) of the APP gene, developing a progressive dementia at 57 years and A beta and tau pathologies in cerebrospinal fluid studies. However, the brother and sister showed different clinical and neuroimaging features, suggesting different A beta pathologies for each sibling. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2019.11.009

Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model

Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 40 ( 1 ) 214 - 224 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS INC

The ubiquitin-proteasome system (UPS) and autophagy are two major pathways to degrade misfolded proteins that accumulate under pathological conditions. When UPS is overloaded, the degeneration pathway may switch to autophagy to remove excessive misfolded proteins. However, it is still unclear whether and how this switch occurs during cerebral ischemia. In the present study, transient middle cerebral artery occlusion (tMCAO) resulted in accelerated ubiquitin-positive protein aggregation from 0.5 h of reperfusion in mice brain after 10, 30 or 60 min of tMCAO. In contrast, significant reduction of p62 and induction of LC3-II were observed, peaking at 24 h of reperfusion after 30 and 60 min tMCAO. Western blot analyses showed an increase of BAG3 and HDAC6 at 1 or 24 h of reperfusion that was dependent on the ischemic period. In contract, BAG1 decreased at 24 h of reperfusion after 10, 30 or 60 min of tMCAO after double immunofluorescent colocalization of ubiquitin, HSP70, p62 and BAG3. These data suggest that a switch from UPS to autophagy occurred between 10 and 30 min of cerebral ischemia depending on the BAG1/BAG3 ratio and level of HDAC6.

DOI： 10.1177/0271678X18810617

A dramatic increase in serum CK levels after switching from oral to intravenous administration of LEV

Mami Takemoto, Taijun Yunoki, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Jingwei Shang, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 1 ) 39 - 41 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The authors report on a 22-year-old Japanese woman who started oral administration of 1000 mg levetiracetam (LEV) for her epilepsy after the second convulsive seizure. She was free from seizures for the subsequent 111 days, but a third tonic-clonic seizure happened and she was transferred to our hospital (Day 1). Her consciousness state was drowsy and 1000 mg LEV continued for two days, but intravenously. Although her state became clear, her serum creatine kinase (CK), myoglobin (Mb), and creatine (Cre) levels were significantly elevated (18 179 IU/L, 2783 ng/mL, and 0.8 mg/mL) with a peak at Day 5 of CK 26, 189 IU/L. After stopping intravenous injection of LEV, serum CK returned to its normal level promptly. The present case suggests that we should take more care in monitoring for rhabdomyolysis on switching from oral to intravenous administration of LEV.

DOI： 10.1111/ncn3.12336

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology

Koji Abe, Jingwei Shang, Xiaowen Shi, Toru Yamashita, Nozomi Hishikawa, Mami Takemoto, Ryuta Morihara, Yumiko Nakano, Yasuyuki Ohta, Kentaro Deguchi, Masaki Ikeda, Yoshio Ikeda, Koichi Okamoto, Mikio Shoji, Masamitsu Takatama, Motohisa Kojo, Takeshi Kuroda, Kenjiro Ono, Noriyuki Kimura, Etsuro Matsubara, Yosuke Osakada, Yosuke Wakutani, Yoshiki Takao, Yasuto Higashi, Kyoichi Asada, Takehito Senga, Lyang Ja Lee, Kenji Tanaka

Journal of Alzheimer's Disease 73 ( 1 ) 217 - 227 2020

Publishing type：Research paper (scientific journal)

© 2020-IOS Press and the authors. All rights reserved. Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid-β (Aβ), plasma tau, and serum antibodies for Aβ1-42 are not yet well established. Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology. Methods: With only 1.5μl of serum, we examined a new target plate 'BLOTCHIP®' plus a matrix-Assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n=100), MCI (n=60), and AD (n=99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains. Results: Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (∗∗∗p<0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains. Conclusion: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.

DOI： 10.3233/JAD-191016

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology

Koji Abe, Jinwei Shang, Xiaowen Shi, Toru hita Yamas, Nozomi Hishikawa, Mami Takemoto, Ryuta Morihara, Yumiko Nakano, Yasuyuki Ohta, Kentaro Deguchi, Masaki Ikeda, Yoshio Ikeda, Koichi Okamoto, Mikio Shoji, Masamitsu Takatama, Motohisa Kojo, Takeshi Kuroda, Kenjiro Ono, Noriyuki Kimura, Etsuro Matsubara, Yosuke Osakada, Yosuke Wakutani, Yoshiki Takao, Yasuto Higashi, Kyoichi Asada, Takehito Senga, Liang-Ja Lee, Kenji Tanaka

JOURNAL OF ALZHEIMERS DISEASE 73 ( 1 ) 217 - 227 2020

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid-beta(A beta), plasma tau, and serum antibodies for A beta(1-42 )are not yet well established.Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.Methods: With only 1.5 mu l of serum, we examined a new target plate "BLOTCHIP (R)" plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.Results: Apart from A beta or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain A beta deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.Conclusion: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.

DOI： 10.3233/JAD-191016

A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption. International journal

Yuting Bian, Toru Yamashita, Yuki Taira, Jingwei Shang, Keiichiro Tsunoda, Tian Feng, Ryo Sasaki, Xia Liu, Xiaowen Shi, Koh Tadokoro, Emi Nomura, Namiko Matsumoto, Yusuke Osakada, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Current neurovascular research 17 ( 3 ) 286 - 293 2020

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. METHODS: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. RESULTS: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. CONCLUSION: The present study provided an evidence of Neumentix's anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

DOI： 10.2174/1567202617666200517105727

Early Emergence of Neuropsychiatric Symptoms in Cognitively Normal Subjects and Mild Cognitive Impairment

Keiichiro Tsunoda, Toru Yamashita, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Emi Nomura, Ryuta Morihara, Yumiko Nakano, Yoshiaki Takahashi, Noriko Hatanaka, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 73 ( 1 ) 209 - 215 2020

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

The world is rapidly aging and facing an increase in the number of dementia patients, so it is important to detect the preclinical stage of dementia in such countries. We examined both cognitive and affective functions among cognitively normal control (n = 218), mild cognitive impairment (MCI, n = 146), and Alzheimer's disease (AD, n = 305) subjects using two evaluation tools for behavioral and psychological symptoms of dementia (BPSD) [Abe's BPSD score (ABS) and mild behavioral impairment (MBI)]. BPSD were present in 12.4% (ABS) and 9.6% (MBI) of cognitively normal people, 34.9% and 32.2% in MCI subjects, and 66.2% and 51.1% in AD patients. Both ABS (p < 0.05) and MBI (( )p < 0.01) score showed worse score with cognitive decline of the Mini-Mental State Examination in the AD group in BPSD-positive participants. Similar correlations were found in all participants in AD group ((parallel to parallel to)p < 0.01 versus ABS and MBI). Among the subscales in BPSD-positive participants, an apathy/indifference score of ABS and a decreased motivation of MBI showed significant differences in AD patients compared to the control and MCI subjects (**p < 0.01). In addition, subscale analyses further showed a downward trend from the control to MCI and AD subjects in four ABS subscales and three MBI subscales. The present study showed the preclinical presence of BPSD in cognitively normal people, more so in MCI subjects, and ABS detected BPSD more sensitively than MBI in all three groups.

DOI： 10.3233/JAD-190669

The Efficacy of Sertraline, Escitalopram, and Nicergoline in the Treatment of Depression and Apathy in Alzheimer's Disease: The Okayama Depression and Apathy Project (ODAP). International journal

Mami Takemoto, Yasuyuki Ohta, Nozomi Hishikawa, Toru Yamashita, Emi Nomura, Keiichiro Tsunoda, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Yoshio Omote, Koji Abe

Journal of Alzheimer's disease : JAD 76 ( 2 ) 769 - 772 2020

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Neuropsychiatric symptoms of dementia such as depression and apathy in patients with Alzheimer's disease (AD) are associated with a lower quality of life. OBJECTIVE: We aimed to determine the efficacy of two antidepressants and one antipathy drug in the treatment of depression and apathy in AD patients. METHODS: In the present study, we evaluated the efficacy of sertraline (n = 11; average dose = 31.8 mg), escitalopram (n = 13; average dose = 7.3 mg), and nicergoline (n = 9; average dose = 14.5 mg) in treating depression and apathy over a period of 3 months (M).The 33 patients with AD demonstrated high Geriatric Depression Scale (GDS) (>5) or a high Apathy Scale (AS) (>16) scores. RESULTS: The patients receiving escitalopram treatment showed a significant improvement in GDS score from baseline (8.2±3.5) to 3 M (5.7±2.6, p = 0.04), and the patients receiving sertraline treatment showed a significant improvement in AS score from baseline (20.8±5.2) to 3 M (16.8±6.1, p = 0.05); however, no significant changes were noted in patients receiving nicergoline. CONCLUSION: These results provide novel information on the efficacy of sertraline and escitalopram in the treatment of apathy and depression, respectively, in patients with AD.

DOI： 10.3233/JAD-200247

Female dominant association of sarcopenia and physical frailty in mild cognitive impairment and Alzheimer's disease

Yasuyuki Ohta, Emi Nomura, Noriko Hatanaka, Yosuke Osakada, Namiko Matsumoto, Ryo Sasaki, Keiichiro Tsunoda, Mami Takemoto, Koh Tadokoro, Nozomi Hishikawa, Yosuke Wakutani, Toru Yamashita, Kota Sato, Yoshio Omote, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 70 96 - 101 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Associations of sarcopenia and physical frailty in cognitive and affective (depression, apathy, and behavioral and psychological symptoms of dementia) functions of mild cognitive impairment (MCI) and Alzheimer's disease (AD) were not fully evaluated previously, especially not for gender differences. 165 AD, 84 MCI, and 48 control participants (175 female, 122 male) were evaluated for cognitive, affective, activities of daily living (ADL), and physical functions associated with sarcopenia and physical frailty. In both sexes, cognitive and affective functions, ADL, and physical functions worsened in MCI and AD compared to control subjects. Physical dysfunctions, especially slow gait speed (3 m up and go test), were significantly associated with cognitive, affective, and ADL declines in participants (control subjects, MCI, and AD) of each gender, which were especially noticeable in females. The present study may be the first to suggest significant associations of sarcopenia and physical frailty with cognitive and affective functions of MCI and AD, especially in females. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2019.08.062

Intracranial invasive fungal aneurysm due to Aspergillus sinusitis successfully treated by voriconazole plus internal carotid artery ligation therapy in an aged woman

Mami Takemoto, Yasuyuki Ohta, Koh Tadokoro, Ryo Sasaki, Yoshiaki Takahashi, Kota Sato, Toru Yamashita, Nozomi Hishikawa, Jingwei Shang, Masafumi Hiramatsu, Kenji Sugiu, Tomohito Hishikawa, Isao Date, Koji Abe

NEUROLOGY ASIA 24 ( 4 ) 363 - 367 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ASEAN NEUROLOGICAL ASSOC

A fungal carotid aneurysm is an infrequently occurring infectious aneurysm that is usually treated by antifungal therapy plus surgical debridement of the infected vessel. We herein report an extremely rare case involving a patient with a medical history of bladder cancer treated by Bacillus Calmette-Guerin (BCG) who developed a fungal aneurysm of the internal carotid artery and thrombosis of the superior ophthalmic vein caused by maxillary Aspergillus sinusitis. The patient was successfully treated by antifungal, anticoagulant, and antiplatelet drugs combined with internal carotid artery ligation therapy. Internal carotid artery fungal aneurysm is associated with a high mortality rate, but the present case suggests that it can be successfully treated by antifungal therapy combined with a less invasive endovascular therapy.

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people

Nozomi Hishikawa, Yoriko Takahashi, Yusuke Fukui, Ryo Tokuchi, Junichi Furusawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Koji Abe

Neurological Research 41 ( 11 ) 1001 - 1007 2019.11

Language：English Publishing type：Research paper (scientific journal)

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga (‘Yoga-plus’) among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe’s behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

DOI： 10.1080/01616412.2019.1672380

Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction.

Ryo Sasaki, Yasuyuki Ohta, Kota Sato, Koh Tadokoro, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Hiroyuki Ishiura, Shoji Tsuji, Koji Abe

Internal medicine (Tokyo, Japan) 58 ( 21 ) 3163 - 3165 2019.11

Language：English Publishing type：Research paper (scientific journal)

A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.

DOI： 10.2169/internalmedicine.2765-19

時間で追う脳虚血の病態と治療:(2)亜急性期虚血脳内グリア細胞から神経細胞を誘導するダイレクトリプログラミング法の確立

山下徹, 商敬偉, 中野由美子, 森原隆太, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

脳循環代謝 31 ( 1 ) 65 - 65 2019.11

パーキンソン病とレビー小体型認知症の検査所見やmicrobleeds出現頻度の違いについて

武本麻美, 佐藤恒太, 太田康之, 山下徹, 菱川望, 阿部康二

臨床神経学 59 ( Suppl. ) S266 - S266 2019.11

Chronic cerebral hypoperfusion alters amyloid-beta transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse

Jingwei Shang, Tom Yamashita, Feng Tian, Xianghong Li, Xia Liu, Xiaowen Shi, Yumiko Nakano, Keiichiro Tsunoda, Emi Nomura, Ryo Sasaki, Koh Tadokoro, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1723 146379 - 146379 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Abnormal accumulation of amyloid-beta (A beta) peptide defines progression of Alzheimer's disease (AD) pathology in brain. Here, we investigated expressive changes of two main All transport receptors low-density lipoprotein receptor related protein-1 (LRP1) and receptor for advanced glycation end products (RAGE) in a novel AD mice (APP23) with chronic cerebral hypoperfusion (CCH) model, moreover, examined a protective effect of a free radical scavenger edaravone (Eda). In contrast to wild type (WT) and APP23 mice, CCH strongly accelerated abnormal A beta 40 depositions and cerebral amyloid angiopathy (CAA) pathology, increased both LRP1 and RAGE expressions in brain parenchyma, while a decrease of LRP1 and an increase of RAGE were observed in vascular endothelial cells at age 12 months (M) of AD mice. Furthermore, CCH strongly increased expressions of two hypoxia-related proteins hypoxia inducible factor-1 alpha (HIF-1 alpha) and heme oxygenase-1 (HO-1), two oxidative-related proteins 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and decreased both two vital nutrient transporter proteins major facilitator super family domain containing 2a (Mfsd2a) and glucose transporter 1 (Glut1) expressions. Such the above abnormal pathological changes were significantly ameliorated by edaravone treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology causing double imbalances of A beta efflux and influx transport related proteins in the cortical blood vessels in AD mice, and that such a neuropathologic abnormality was greatly ameliorated by Eda.

DOI： 10.1016/j.brainres.2019.146379

A unique stroke case with contralateral sulcal hyperintensity on fluid-attenuated inversion recovery image changed to linear serpiginous structures

Yosuke Osakada, Yoshiaki Takahashi, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 6 ) 351 - 353 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures.

DOI： 10.1111/ncn3.12327

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people

Nozomi Hishikawa, Yoriko Takahashi, Yusuke Fukui, Ryo Tokuchi, Junichi Furusawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGICAL RESEARCH 41 ( 11 ) 1001 - 1007 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga (?Yoga-plus?) among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ? 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe?s behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ? 5) and AS (AS ? 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

DOI： 10.1080/01616412.2019.1672380

A Japanese patient with a VCP mutation c.290G > A (p.G97E) presenting a rapid progressive respiratory failure Reviewed

Emi Nomura, Yasuyuki Ohta, Kota Sato, Yuko Kawahara, Mami Takemoto, Yoshiaki Takahashi, Namiko Matsumoto, Taijun Yunoki, Toru Yamashita, Nozomi Hishikawa, Ichizo Nishino, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 6 ) 361 - 364 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder caused by mutations in the valosin-containing protein (VCP) gene. IBMPFD usually presents progressive limb muscle weakness resulting in wheelchaired after mean course of 9 years with myopathy, and Paget's osteolytic lesions and frontotemporal dementia (FTD) rarely present respiratory failure. Different from previous reports, we reported a Japanese IBMPFD patient with a VCP mutation c.290G > A (p.G97E), presenting a progressive respiratory failure accompanied by wheelchaired in only 6 years after myopathy onset, suggesting unique relationship between clinical severity and c.290G > A (p.G97E) mutation of VCP gene in Japanese.

DOI： 10.1111/ncn3.12330

見逃したくない治療可能な小脳性運動失調症 PEX10変異による小脳失調症

山下徹, 三井純, 下澤伸行, 高島茂雄, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 松川敬志, 石浦浩之, 吉村淳, 土井晃一郎, 森下真一, 辻省次, 阿部康二

臨床神経学 59 ( Suppl. ) S45 - S45 2019.11

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