研究者詳細 - 山下　徹

論文 - 山下　徹

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Recovery from hypoxemia and Hypercapnia following noninvasive pressure support ventilation in a patient with statin-associated necrotizing myopathy: a case report. 査読国際誌

Yuriko Yamamura, Yoshinori Matsumoto, Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Toru Yamashita, Masahiro Yamamura, Ken-Ei Sada, Koji Abe, Jun Wada

BMC pulmonary medicine 20 ( 1 ) 156 - 156 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Statin-associated necrotizing myopathy (SANM) is a rare autoimmune disorder caused by administration of statins. SANM is characterized by weakness due to necrosis and regeneration of myofibers. Here we report the first case of SANM with acute respiratory failure treated with noninvasive pressure support ventilation in addition to immunosuppressants. CASE PRESENTATION: A 59-year-old woman who had been treated with 2.5 mg/day of rosuvastatin calcium for 5 years stopped taking the drug 4 months before admission to our hospital due to elevation of creatine kinase (CK). Withdrawal of rosuvastatin for 1 month did not decrease the level of CK, and she was admitted to our hospital due to the development of muscle weakness of her neck and bilateral upper extremities. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies were positive. Magnetic resonance imaging showed myositis, and muscle biopsy from the right biceps brachii muscle showed muscle fiber necrosis and regeneration without inflammatory cell infiltration, suggesting SANM. After the diagnosis, she received methylprednisolone pulse therapy (mPSL, 1 g/day × 3 days, twice) and subsequent oral prednisolone therapy (PSL, 30 mg/day for 1 month, 25 mg/day for 1 month and 22.5 mg/day for 1 month), leading to improvement of her muscle weakness. One month after the PSL tapering to 20 mg/day, her muscle weakness deteriorated with oxygen desaturation (SpO2: 93% at room air) due to hypoventilation caused by weakness of respiratory muscles. BIPAP was used for the management of acute respiratory failure in combination with IVIG (20 g/day × 5 days) followed by mPSL pulse therapy (1 g/day × 3 days), oral PSL (30 mg/day × 3 weeks, then tapered to 25 mg/day) and tacrolimus (3 mg/day). Twenty-seven days after the start of BIPAP, she was weaned from BIPAP with improvement of muscle weakness, hypoxemia and hypercapnia. After she achieved remission with improvement of muscle weakness and reduction of serum CK level to a normal level, the dose of oral prednisolone was gradually tapered to 12.5 mg/day without relapse for 3 months. CONCLUSIONS: Our report provides new insights into the role of immunosuppressants and biphasic positive airway pressure for induction of remission in patients with SANM.

DOI： 10.1186/s12890-020-01195-7

A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption. 査読国際誌

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年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Cerebral ischemia causes strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which was proved to be beneficial against inflammatory response. Therefore, we investigated Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice. METHODS: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterwards. 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 calcium-binding 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 the 5 days after tMCAO. Conclusios: Our 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 potential therapeutic agent for stroke.

DOI： 10.2174/1567202617666200517105727

Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice. 査読国際誌

Koh Tadokoro, Yusuke Fukui, Toru Yamashita, Xia Liu, Keiichiro Tsunoda, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Feng Tian, Ryo Sasaki, Namiko Matsumoto, Emi Nomura, Xiaowen Shi, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 ( 5 ) 104743 - 104743 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. METHODS: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). RESULTS: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. CONCLUSIONS: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104743

Diabetic painful truncal neuropathy with hypohidrosis and facial palsy

Keiichiro Tsunoda, Yoshio Omote, Nozomi Hishikawa, Ken Ikegami, Yumiko Nakano, Kota Sato, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 155 - 157 2020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：WILEY

Truncal neuropathy is a rare phenotype of diabetic neuropathy. Here, we report the first case of diabetic painful truncal neuropathy complaining of back pain with hypohidrosis confirmed by a sweat test accompanied by cranial nerve palsy. The patient had poorly controlled type 2 diabetes mellitus and suffered from back pain followed by facial palsy. After pulse therapy with methylprednisolone facial palsy improved, but back pain was intractable with a loss of body weight. The sweat test showed hypohidrosis on the back and soles on his feet. Sural nerve biopsy revealed decreased small fibers and mild axonopathy. After palliative therapy, his symptoms gradually improved.

DOI： 10.1111/ncn3.12370

A spontaneous recovery of anti-galactocerebroside antibody-associated encephalitis without evidence of Mycoplasma infection

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

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 164 - 166 2020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：WILEY

Anti-galactocerebroside (Gal-C) antibody is characteristic of encephalomyelitis and Guillain-Barre syndrome subsequent to mycoplasma infection. Here, we report a 75-year-old Japanese man who presented somnolence, signs of meningeal irritation, and parkinsonian features with positive serum inflammatory markers and cerebrospinal fluid (CSF) pleocytosis. Although anti-Mycoplasma pneumoniae antibody was negative, anti-Gal-C antibody was later detected in his serum. The present case recovered spontaneously without any other specific therapies.

DOI： 10.1111/ncn3.12379

Discrepancy of subjective and objective sleep problems in Alzheimer's disease and mild cognitive impairment detected by a home-based sleep analysis 査読国際誌

Koh Tadokoro, Yasuyuki Ohta, Nozomi Hishikawa, Emi Nomura, Yosuke Wakutani, Yoshiki Takao, Yoshio Omote, Mami Takemoto, Toru Yamashita, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 74 76 - 80 2020年4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：ELSEVIER SCI LTD

There is a strong relationship between Alzheimer's disease (AD) and sleep problems, and a sleep condition is informative for evaluating the AD status. In the present study, we evaluated subjective sleep problems in AD and mild cognitive impairment (MCI) with self-check questionnaires and objective sleep problems with a convenient home-based portable device, WatchPAT. A total of 63 subjects with normal cognition (NC) (n = 22), MCI (n = 20), and AD (n = 21) were cross-sectionally investigated. AD patients showed a better self-check Pittsburgh sleep quality index (PSQI) score (*p < 0.05) than NC and MCI patients. On the other hand, WatchPAT analysis showed a significantly reduced rapid eye movement (REM) sleep (*p < 0.05) and increased light sleep in AD patients (*p < 0.05) compared with NC subjects, and mildly reduced REM and increased light sleep in MCI subjects. The present study revealed a gap between the subjective self-check sleep questions and the objective WatchPAT analysis in AD patients. Thus, a home-based sleep study with WatchPAT is a useful tool to detect an objective sleep problem in AD and the risk of MCI conversion into AD.

DOI： 10.1016/j.jocn.2020.01.085

LGI1 antibody-associated limbic encephalitis started from unilateral basal ganglia to medial temporal lobe and insula

Xia Liu, Yoshio Omote, Yosuke Osakada, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 68 - 71 2020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：WILEY

Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis is a rare autoimmune encephalitis. Here, we report a 39-year-old woman presented with generalized tonic-clonic seizures, night delirium, bilateral upper limb tremor, and hyponatremia. Her symptoms did not improve with initial steroid therapy, and brain magnetic resonance imaging (MRI) showed a progression of abnormalities from right basal ganglia to medial temporal lobe and insula. The presence of LGI1 antibodies in the patient's serum confirmed the clinical diagnosis. After the combined treatments of methylprednisolone, plasma exchange, and intravenous immunoglobulin, her clinical symptoms resolved completely.

DOI： 10.1111/ncn3.12351

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：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

A juvenile case of idiopathic hypertrophic pachymeningitis involved cavernous sinus and proximal trigeminal nerve

Zhihong Bian, Yoshio Omote, Koh Tadokoro, Ken Ikegami, Yosuke Osakada, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 82 - 85 2020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：WILEY

Idiopathic hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial or spinal dura mater, which is primarily reported in adults. Here, we report a juvenile idiopathic HP case presenting diplopia and multiple cranial nerve palsies. Although cranial magnetic resonance imaging (MRI) shows evident lesions in cavernous sinus and preganglionic segment of trigeminal nerve, only cerebrospinal fluid (CSF) showed elevated protein (55 mg/dL) and myelin basic protein (MBP, 355 pg/mL) but negative systemic inflammatory markers. Steroid therapy greatly improved the symptom and the CSF data in 1 month.

DOI： 10.1111/ncn3.12355

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

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

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 72 482 - 484 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Autosomal dominant amyloid precursor protein (APP) mutations in familial Alzheimer's disease accelerate the amyloid beta (Aβ) 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 Aβ and tau pathologies in cerebrospinal fluid studies. However, the brother and sister showed different clinical and neuroimaging features, suggesting different Aβ pathologies for each sibling.

DOI： 10.1016/j.jocn.2019.11.009

A novel homoplasmic mitochondrial DNA mutation (m.13376T>C, p.I347T) of MELAS presenting characteristic medial temporal lobe atrophy. 査読国際誌

Ryo Sasaki, Yasuyuki Ohta, Noriko Hatanaka, Koh Tadokoro, Emi Nomura, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yoshio Omote, Eisaku Morimoto, Sanae Teshigawara, Jun Wada, Yu-Ichi Goto, Koji Abe

Journal of the neurological sciences 408 116460 - 116460 2020年1月

Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model. 査読国際誌

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 : official journal of the International Society of Cerebral Blood Flow and Metabolism 40 ( 1 ) 214 - 224 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

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：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. 査読国際誌

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 : JAD 73 ( 1 ) 217 - 227 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Early Emergence of Neuropsychiatric Symptoms in Cognitively Normal Subjects and Mild Cognitive Impairment. 査読国際誌

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 Alzheimer's disease : JAD 73 ( 1 ) 209 - 215 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

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 (||||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

Female dominant association of sarcopenia and physical frailty in mild cognitive impairment and Alzheimer's disease. 査読国際誌

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 : official journal of the Neurosurgical Society of Australasia 70 96 - 101 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

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：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.

Chronic cerebral hypoperfusion alters amyloid-β transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse. 査読国際誌

Jingwei Shang, Toru 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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Abnormal accumulation of amyloid-β (Aβ) peptide defines progression of Alzheimer's disease (AD) pathology in brain. Here, we investigated expressive changes of two main Aβ 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 Aβ40 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-1α (HIF-1α) 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 Aβ 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

Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction. 査読

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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people. 査読国際誌

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年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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