研究者詳細 - 福井　裕介

論文 - 福井　裕介

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Flow-metabolism uncoupling in the cervical spinal cord of ALS patients 査読

Toru Yamashita, Tetsuhiro Hatakeyama, Kota Sato, Yusuke Fukui, Nozomi Hishikawa, Yasuyuki Ohta, Yoshihiro Nishiyama, Nobuyuki Kawai, Takashi Tamiya, Koji Abe

NEUROLOGICAL SCIENCES 38 ( 4 ) 659 - 665 2017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：SPRINGER-VERLAG ITALIA SRL

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. In ALS, both glucose consumption and neuronal intensity reportedly decrease in the cerebral motor cortex when measured by positron emission tomography (PET). In this study, we evaluated cervical spinal glucose metabolism, blood flow, and neuronal intensity of 10 ALS patients with upper extremity (U/E) atrophy both with F-18-2-fluoro-2-deoxy-d-glucose (F-18-FDG) PET and C-11-flumazenil (C-11-FMZ) PET. On the ipsilateral side of C5 and T1 levels, F-18-FDG uptake increased significantly (*p < 0.05), and was correlated with the rate of progression of the ALS FRS-R-U/E score (R = 0.645, *p = 0.041). Despite this hyperglucose metabolism, the C-11-FMZ PET study did not show a coupled increase of spinal blood flow even though neuronal intensity did not decrease. These results indicate a strong correlation between hyperglucose metabolism and ALS progression alongside the uncoupling of flow-metabolism. This mechanism, which could result in subsequent motor neuronal death, may be a potential therapeutic target for ALS.

DOI： 10.1007/s10072-017-2823-y

Satisfaction with dietary life affects oral health-related quality of life and subjective well-being in very elderly people.

Toshimitsu Iinuma, Yasumichi Arai, Midori Takayama, Michiyo Takayama, Yukiko Abe, Yusuke Osawa, Motoko Fukumoto, Yusuke Fukui, Yohei Shioda, Nobuyoshi Hirose, Kazuo Komiyama, Nobuhito Gionhaku

Journal of oral science 59 ( 2 ) 207 - 213 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）

Age-related deterioration in physical and oral health reduces healthy life expectancy and is thus an important problem for very elderly people. We investigated the effects of satisfaction with dietary life (SDL) in everyday life on oral health-related quality of life (OHRQoL) and subjective well-being and examined associations between these factors. We evaluated 426 elders aged 85 years or older. All participants completed a questionnaire that inquired about age, gender, drinking status, body mass index, cognitive function, disability, and comorbidities, among other covariates. Oral, physical, and mental health conditions were also examined. Associations of questionnaire results for SDL with items on subjective well-being (Philadelphia Geriatric Center Morale Scale [PGC] and World Health Organization-5 [WHO-5]) and OHRQoL (Geriatric Oral Health Assessment Index [GOHAI]) were confirmed with multiple logistic regression analysis. In a multivariate model adjusted for various confounders, participants with self-reported "enjoyable" SDL had significantly lower risks for having the lowest scores on the GOHAI, PGC, and WHO-5 (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.277-0.762; OR = 0.589, 95% CI = 0.348-0.996; and OR = 0.452, 95% CI = 0.263-0.775, respectively). These associations remained after further adjustment for number of teeth.

DOI： 10.2334/josnusd.16-0414

Cognitive and affective functions associated with insomnia: a population-based study 査読

Nozomi Hishikawa, Yusuke Fukui, Kota Sato, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGICAL RESEARCH 39 ( 4 ) 331 - 336 2017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：TAYLOR & FRANCIS LTD

Objectives: The number of patients with insomnia is rapidly increasing as society ages. The influence of insomnia on cognitive, affective, and activities of daily living (ADL) functions has not been fully studied.Methods: Participants were 142 residents of a local super-aged community who underwent health check-ups provided by the local government. Participants completed cognitive, affective and ADL function tests including the MMSE. We divided participants into two subgroups based on Athens Insomnia Scale (AIS) scores (AIS3 and AIS4) and compared cognitive, affective, and ADL functions by sex and age.Results: Subjective insomnia (AIS4) was found in 36.2% of participants and was more frequent in females than males. No differences were found in cognitive function between the AIS subgroups. For both sexes, Geriatric Depression Scale scores were significantly higher in the AIS4 subgroup than the AIS3 subgroup. Apathy Scale scores were significantly higher in males in the AIS4 subgroup. Of the AIS subscales, sleepiness during the day' was significantly higher in females than males (**p<0.01), especially in those aged 75years (**p<0.01). This group of older females also showed a significantly lower Trail Making Test scores (*p<0.05).Discussion: Insomnia was present in 36.2% of the population in a Japanese super-aged community. Those with insomnia showed more depressive symptoms (both sexes) and males showed more apathy. The most distinct characteristic of females aged 75years was a high frequency of daytime sleepiness, possibly related to a decline in attention and executive function.

DOI： 10.1080/01616412.2017.1281200

Differences between the behavioral and psychological symptoms of Alzheimer's disease and Parkinson's disease 査読

Ryo Tokuchi, Nozomi Hishikawa, Kota Sato, Noriko Hatanaka, Yusuke Fukui, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 369 278 - 282 2016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：ELSEVIER SCIENCE BV

Aim: We compared the behavioral and psychological symptoms of Alzheimer's disease (AD) and Parkinson's disease (PD) in order to determine the characteristic features of each disorder.
Methods: For this retrospective cohort study, we compared the behavioral and psychological symptoms of 288 AD patients and 189 PD patients (mean age, 74.6 +/- 5.9 and 73.0 +/- 8.7 years respectively). Symptoms were evaluated using the geriatric depression scale (GDS), apathy scale (AS), and Abe's behavioral and psychological symptoms of dementia score (ABS).
Results: AD patients had higher AS and ABS scores than PD patients. A gender-dependent comparison showed that ABS scores were worse in female AD patients than in female PD patients (p=0.001). A subscale analysis of ABS scores revealed that male AD patients were only significantly different from male PD patients in I item, whereas female AD patients were significantly different from female PD patients in 4 items. Among patients with mild cognitive decline, no differences in affective scores were observed. Alternatively, among patients with moderate cognitive decline, affective scores on all 3 scales were worse in PD patients than in AD patients.
Conclusions: The present age-and gender-matched retrospective analysis identified greater behavioral and psychological disease severity in female AD patients relative to female PD patients, and greater affective severity in PD patients versus AD patients with a similar degree of cognitive decline. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.08.053

Effects of Pretreatment with Warfarin or Rivaroxaban on Neurovascular Unit Dissociation after Tissue Plasminogen Activator Thrombolysis in Ischemic Rat Brain 査読

Jingwei Shang, Toru Yamashita, Syoichiro Kono, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xianghong Li, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 25 ( 8 ) 1997 - 2003 2016年8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 SCIENCE BV

Background: Warfarin and rivaroxaban are highly effective in reducing stroke risk in patients with atrial fibrillation (AF). However, their effects on anticoagulation and neurovascular unit (NVU) change remain elusive. In this study, we assessed the risks and benefits of pre-treatment with warfarin or rivaroxaban after tissue-type plasminogen activator (tPA) thrombolysis in ischemic rat brain. Methods: Pretreatment with warfarin (.2 mg/kg/day), low dose rivaroxaban (60 mg/kg/day), high dose rivaroxaban (120 mg/kg/day) or vehicle was performed for 2 weeks, transient middle cerebral artery occlusion (tMCAO) was induced for 90 min, then followed by reperfusion with tPA. At 24 hours (h) after reperfusion, we observed the changes of matrix metalloproteinase-9 (MMP-9), tissue factor, caspase 3 and NVU dissociation. Results: Prothrombin time (PT) was significantly prolonged in the warfarin and rivaroxaban pretreated groups. MMP-9 expression greatly increased in the warfarin group, and this was reduced in the rivaroxaban groups compared with the vehicle group. Tissue factor expression remarkably decreased in the warfarin and rivaroxaban groups. The number of caspase 3-positive cells had no difference among all the groups. Marked dissociations between astrocyte foot processes and the basal lamina or pericytes were observed in the warfarin pretreated group, but such dissociations were improved in the rivaroxaban groups. Conclusions: Our present study shows that pre-treatment with rivaroxaban was noninferior to warfarin in the anticoagulation, but a lower risk of NVU dysfunction and dissociation after tPA treatment in rivaroxaban. This finding could partly explain the mechanism of reducing hemorrhagic complications by rivaroxaban in clinical studies.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.04.002

Peripheral arterial endothelial dysfunction of neurodegenerative diseases 査読

Yusuke Fukui, Nozomi Hishikawa, Jingwei Shang, Kota Sato, Yumiko Nakano, Ryuta Morihara, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 366 94 - 99 2016年7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 SCIENCE BV

This study evaluates endothelial functions of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and spinocerebellar ataxia (SCA).
The reactive hyperemia index (RHI) of peripheral arterial tonometry and serological data were compared between age- and gender-matched normal controls (n = 302) and five disease groups (ALS; n = 75, PD; n = 180, PSP; n = 30, MSA; n = 35, SCA; n = 53). Correlation analyses were performed in ALS with functional rating scale-revised (FRS-R), and in PD with the Hehn-Yahr scale (H-Y) and a heart to mediastinum ratio using I-123-MIBG scintigraphy (MIBG).
The RHI of ALS and PD, but not of PSP, MSA or SCA, were significantly lower than normal controls (p < 0.01). ALS showed a negative correlation of RHI with serum triglycerides (TG) and immunoreactive insulin (IRI) levels, but not with disease severity (FRS-R) or rates of disease progression (Delta FRS-R). On the other hand, PD showed a negative correlation of RHI with a progressive disease severity (H-Y) and a positive correlation of RHI with early/delayed MIBG scintigraphy, but not with serological data.
The present study demonstrated significant declines of peripheral arterial endothelial functions in ALS and PD. The RHI of ALS was more correlated with disease duration and serum parameters while the RHI of PD was more correlated with disease severity and MIBG, suggesting different mechanisms of endothelial dysfunction. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.04.042

Age-dependent cognitive and affective differences in Alzheimer's and Parkinson's diseases in relation to MRI findings 査読

Ryo Tokuchi, Nozomi Hishikawa, Kota Sato, Noriko Hatanaka, Yusuke Fukui, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 365 3 - 8 2016年6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 SCIENCE BV

Objective: To compare age-dependent changes in cognitive and affective functions related to white matter changes between patients with Alzheimer's disease (AD) and Parkinson's disease (PD).
Methods: We retrospectively compared age-dependent cognitive and affective functions in 216 AD patients, 153 PD patients, and 103 healthy controls with cerebral white matter lesions (WMLs), periventricular hyperintensity (PVH), deep white matter hyperintensity (DWMH), micro-bleeds (MBs), and lacunar infarcts (LIs).
Results: The average mini-mental state examination (MMSE) scores were 19.6 +/- 6.1 and 26.8 +/- 3.6 in AD and PD patients, respectively. Significant decreases were found in the MMSE score, Hasegawa's dementia scale-revised (HDS-R) score, frontal assessment battery score, and Abe's BPSD score (ABS) among the age-dependent AD subgroups and in the MMSE, HDS-R, Montreal cognitive assessment, geriatric depression scale, and ABS scores among the age-dependent PD subgroups; they were worse in AD patients. White matter changes were observed in > 88% and > 72% of patients with AD and PD, respectively. An age-dependent direct comparison of AD and PD showed significant differences in the PVH and DWMH grades, and numbers of MBs and LIs.
Conclusion: WML-related cognitive and affective functions worsen with age in AD and PD patients; however, the abnormalities were more frequent and stronger in AD patients. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.03.031

Characteristic features of cognitive, affective and daily living functions of late-elderly dementia 査読

Nozomi Hishikawa, Yusuke Fukui, Kota Sato, Syoichiro Kono, Toru Yamashita, Yasuyuki Ohta, Kentaro Deguchi, Koji Abe

GERIATRICS & GERONTOLOGY INTERNATIONAL 16 ( 4 ) 458 - 465 2016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：WILEY-BLACKWELL

AimsThe world is rapidly aging, and is facing an increase of late-elderly dementia patients. It is important to investigate the characteristic features of late-elderly dementia in a super-aged country.
MethodsWe examined 1554 patients with cognitive decline in Department of Neurology, Okayama University Hospital, Okayama, Japan, divided into three subgroups according to the age: young-elderly (age 64 years), middle-elderly (age 65-74 years) and late-elderly (age 75 years), and investigated the cognitive, affective and activities of daily living functions (ADL), especially in late-elderly patients compared with young-elderly and middle-elderly patients.
ResultsAmong 1554 patients, Alzheimer's disease dominated at 62%, and age-dependently increased up to 69% in the late-elderly group. The total scores of four cognitive tests were significantly worse with aging for specific subscales of orientation, recall, visual retention, word fluency and so on. In contrast, total scores of the affective tests showed only an increase in the apathy scale in the late-elderly group. Each subgroup showed depressive/depression in 63.2-55.2%, and apathy in 44.2-54.8%. Furthermore, instrumental ADL items significantly deteriorated in the late-elderly group, which statistically correlated with Mini-Mental State Examination score.
ConclusionsThese results show that the late-elderly group is characterized by significant cognitive declines, increasing apathy, and instrumental ADL decrease. The cognitive decline may be related to such affective and ADL declines. Geriatr Gerontol Int 2016; 16: 458-465.

DOI： 10.1111/ggi.12492

Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome. 査読国際誌

N Hishikawa, Y Fukui, K Sato, S Kono, T Yamashita, Y Ohta, K Deguchi, K Abe

European journal of neurology 23 ( 2 ) 339 - 45 2016年2月

記述言語：英語

BACKGROUND AND PURPOSE: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. METHODS: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. RESULTS: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score-Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. CONCLUSIONS: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

DOI： 10.1111/ene.12845

Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy 査読

Yusuke Fukui, Nozomi Hishikawa, Kota Sato, Yumiko Nakano, Ryuta Morihara, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF NEUROLOGY 263 ( 1 ) 61 - 67 2016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：SPRINGER HEIDELBERG

The objective of this study is to determine whether diffusion tensor imaging (DTI) tractography analysis is a potential method for differentiating cerebellar ataxia patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and cortical cerebellar atrophy (CCA). Forty-one MSA-C patients (62.7 +/- A 8.1 years old, mean +/- A SD) and age- and gender-matched 15 CCA patients (63.0 +/- A 8.6 years old) were examined. Tractography was performed using the DTI track module provided in the MedINRIA version 1.9.4, and regions of interest were drawn manually to reconstruct an efferent fiber tract and two afferent fiber tracts via the cerebellum. Compared with CCA, MSA-C patients showed significant declines of fractional anisotropy (FA) values of afferent 1 and 2 (p < 0.01, respectively) and a significant increase of the radial diffusivity (RD) value in afferent 1 (p < 0.05). Receiver-operator characteristic curve analysis showed 85.7 % sensitivity and 75.0 % specificity of FA values in afferent 1 (cutoff value 0.476). Linear regressions showed strong correlations between FA value and disease duration in CCA patients (efferent 1, r = -0.466; afferent 2, r = -0.543; both p < 0.05), and between the FA value and the ratio of the standardized scale for the assessment and rating of ataxia (SARA)/disease duration in MSA-C patients (afferent 1, r = -0.407; p < 0.01). The present DTI tractography newly showed that the FA values of two afferent fiber tracts showed significant declines in MSA-C patients, and afferent 1 showed good diagnostic sensitivity and specificity. When combining the FA values of efferent 1 with disease duration, the present DTI tractography analysis could be useful for differentiating MSA-C and CCA patients.

DOI： 10.1007/s00415-015-7934-x

Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit, Cerebrovascular Remodeling, and Neurovascular Trophic Coupling in Alzheimer's Disease Model Mouse 査読

Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Yusuke Fukui, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 52 ( 1 ) 113 - 126 2016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：IOS PRESS

Although chronic cerebral hypoperfusion (CCH) may affect Alzheimer's disease (AD) pathogenesis, the mechanism remains elusive. In the present study, we investigated the role of CCH on an AD mouse model in neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of galantamine. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral hypoperfusion. CCH exacerbated neuronal loss and decrease of alpha 7 subunit of nicotinic acetylcholine receptors (alpha 7-nAChRs) expression in hippocampus and thalamus at 12 months. Meanwhile, CCH greatly induced advanced glycation end products expression, and blood-brain barrier leakage through observing IgG and MMP9 expressions. Furthermore, a significant number of dramatic enlarged cerebral vessels with remodeling, BDNF/TrkB decreased in neurovascular trophic coupling. The present study demonstrated that CCH strongly enhanced primary AD pathology including neurodegeneration, neurovascular unit disruption, cerebrovascular remodeling and neurovascular trophic coupling damage in AD mice, and that galantamine treatment greatly ameliorated such neuropathologic abnormalities.

DOI： 10.3233/JAD-151126

Chronic Cerebral Hypoperfusion Accelerates Alzheimer's Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model 査読

Yun Zhai, Toru Yamashita, Yumiko Nakano, Zhuoran Sun, Jingwei Shang, Tian Feng, Ryuta Morihara, Yusuke Fukui, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 53 ( 3 ) 893 - 905 2016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：IOS PRESS

Recently, aging societies have been showing an increasingly strong relationship between Alzheimer's disease (AD) and chronic cerebral hypoperfusion (HP). In the present study, we created a new mouse model for AD with HP, and investigated its clinical and pathological characteristics. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral HP. In contrast to simple APP23 mice, cerebral HP exacerbated motor and cognitive dysfunctions with white matter lesions and meningo-parenchymal amyloid-beta (A beta) burdens. Strong cerebrovascular inflammation and severe amyloid angiopathy with cerebrovascular remodeling were also observed in APP23 + HP mouse brains. An acetylcholinesterase inhibitor galantamine improved such clinical dysfunctions, retrieved above neuropathological characteristics, and enhanced nicotinic acetylcholine receptor (nAChR)-binding activity. The present study demonstrates that chronic cerebral HP enhanced cognitive/motor dysfunctions with parenchymal/cerebrovascular A beta accumulation and cerebrovascular remodeling. These neuropathological abnormalities were greatly ameliorated by galantamine treatment associated with nAChR-mediated neuroprotection by allosterically potentiating ligand action.

DOI： 10.3233/JAD-160345

Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer's Disease Mouse Model 査読

Yun Zhai, Toru Yamashita, Yumiko Nakano, Zhuoran Sun, Ryuta Morihara, Yusuke Fukui, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 52 ( 4 ) 1311 - 1319 2016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：IOS PRESS

A rapidly progressing aging society has raised attention to white matter lesions in Alzheimer's disease. In the present study, we applied an AD plus cerebral hypoperfusion (HP) mouse model and investigated the alternation of key protein molecules in the nodal, paranodal, and intermodal sites in the white matter as well as the efficacy of galantamine. Cerebral HP was induced in APP23 mice by bilateral common carotid arteries stenosis with ameroid constrictors. Compared with the wild type and simple APP23 mice, APP23 + HP mice showed a progressive loss of MAG and NF186 from 6 to 12 months, broken misdistribution of MBP, and extended relocation of Na(v)1.6 and AnkG beyond the primary nodal region in the corpus callosum. Such abnormal neuropathological processes were retrieved with galantamine treatment. The present study demonstrated that cerebral HP strongly disrupted white matter integrity (WMI) at intermodal, paranodal, and Ranvier's nodal sites which may be associated with cognitive decline. Galantamine treatment significantly protected such WMI probably by allosterically potentiating ligand action.

DOI： 10.3233/JAD-160120

Differentiating progressive supranuclear palsy from Parkinson's disease by MRI-based dynamic cerebrospinal fluid flow. 査読国際誌

Yusuke Fukui, Nozomi Hishikawa, Kota Sato, Taijun Yunoki, Syoichiro Kono, Kosuke Matsuzono, Yumiko Nakano, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

Journal of the neurological sciences 357 ( 1-2 ) 178 - 82 2015年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The purpose of this study was to clarify the difference between PSP and PD from the viewpoint of dynamic cerebrospinal fluid (CSF) flow focusing on the midbrain aqueduct. METHODS: Thirty-three PD patients (mean age 69.2±7.9) and 35 PSP patients (mean age 70.5±6.6) were included in this study. CSF flow was calculated by 15 images in an equidistant magnetic resonance imaging (MRI) sequence that was taken throughout a cardiac cycle. RESULTS: Absolute values of the velocity (time points of 2-6 and 12-15, *p<0.05), and the width of the CSF velocity (Vheight) (PSP, 5.1±2.3cm/s; PD, 6.0±1.6cm/s, p<0.05) effectively discriminated PSP from PD patients. On the other hand, conventional MRI measurements discriminated well the midbrain aqueduct area (Area) (PSP, 7.7±2.6mm(2); PD, 5.4±1.8mm(2), p<0.01). Two cutoff value lines (Vheight: 4.75, Area: 5.77) of the ROC curve analysis established two areas for discriminating PSP from PD. CONCLUSION: In the present dynamic CSF flow study, it was newly found that mean velocity of each time point and Vheight showed a more significant decline in PSP than in PD patients, providing a sensitive biomarker for differentiating them. The combination of Vheight and Area could further discriminate PSP from PD patients.

DOI： 10.1016/j.jns.2015.07.026

Computerized Touch-panel Screening Tests for Detecting Mild Cognitive Impairment and Alzheimer's Disease 査読

Yusuke Fukui, Toru Yamashita, Nozomi Hishikawa, Tomoko Kurata, Kota Sato, Yoshio Omote, Syoichiro Kono, Taijun Yunoki, Yuko Kawahara, Noriko Hatanaka, Ryo Tokuchi, Kentaro Deguchi, Koji Abe

INTERNAL MEDICINE 54 ( 8 ) 895 - 902 2015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：JAPAN SOC INTERNAL MEDICINE

Objective The increasing population of elderly people in Japan has accelerated the demand for a simple screening test to detect cognitive and affective declines in mild cognitive impairment (MCI) and the early stage of dementia.
Methods We compared the cognitive and affective functions, activities of daily living (ADLs) and the results of four computerized touch-panel screening tests in 41 MCI subjects, 124 patients with Alzheimer's disease (AD) and 75 age-and gender-matched normal controls.
Results All computerized touch-panel games were successfully used to discriminate the AD patients from the normal controls (** p<0.01). Although there were no differences in the findings of the conventional cognitive assessments, the results of the flipping cards game were significantly different (** p<0.01) between the normal controls (19.3 +/- 9.5 sec) and MCI subjects (30.9 +/- 18.4 sec). Three conventional affective assessments, the ADL score, Abe's behavioral and psychological symptoms of dementia (ABS) (** p<0.01) and the apathy scale (AS) (* p<0.05), could be used to discriminate the MCI subjects (ABS, 0.9 +/- 1.5; AS, 12.8 +/- 5.9) from the normal controls (ABS, 0.1 +/- 0.4; AS, 8.9 +/- 5.3).
Conclusion In the present study, all four touch-panel screening tests could be employed to discriminate AD patients from normal controls, whereas only the flipping cards game was effective for distinguishing MCI subjects from normal controls. Therefore, this novel touch-panel screening test may be a more sensitive tool for detecting MCI subjects among elderly patients.

DOI： 10.2169/internalmedicine.54.3931

Dynamic Cerebrospinal Fluid Flow on MRI in Cortical Cerebellar Atrophy and Multiple System Atrophy-cerebellar Type. 査読

Yusuke Fukui, Nozomi Hishikawa, Kota Sato, Syoichiro Kono, Kosuke Matsuzono, Yumiko Nakano, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

Internal medicine (Tokyo, Japan) 54 ( 14 ) 1717 - 23 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The purpose of this study was to examine a new MRI technology, dynamic cerebrospinal fluid (CSF) flow, to examine sporadic cerebellar ataxia patients with cortical cerebellar atrophy (CCA) and multiple system atrophy-cerebellar type (MSA-C). METHODS: Nine CCA patients (3 men and 6 women; mean age: 64.2±6.9 years) and 31 MSA-C patients (13 men and 18 women; mean age: 62.7±6.8 years) were examined by a dynamic CSF flow analysis. All CSF flow data were evaluated by phase contrast-MRI using a 1.5T MRI scanner. The CSF flow was calculated by 15 images in the equidistant MRI sequence which was taken through a cardiac cycle. RESULTS: Compared with the CCA patients, the absolute values of the mean velocity of the MSA-C patients were significantly reduced at time points 5 (CCA, 0.24±0.14 cm/s; MSA-C, 0.13±0.11 cm/s; (*) p<0.05) and 13 (CCA, -0.60±0.37 cm/s; MSA-C, -0.31±0.17 cm/s; (**) p<0.01). Significant correlations in Spearman's rank correlation coefficient were also found in MSA-C patients between the disease duration and the difference between the maximum and minimum velocities (Vheight) (r=-0.429, (*) p<0.05), the minimum velocity of the CSF (Vmin) (r=0.486, (**) p<0.01) or the length of the minor axis of the pons (r=-0.529, (**) p<0.01). The linear regressions between the disease duration and Vheight or Vmin revealed a significant strong correlation only in the MSA-C patients. CONCLUSION: The present CSF flow study showed for the first time that Vheight and Vmin revealed good correlations with the disease duration in the MSA-C patients. Furthermore, the velocity of the prepontine CSF flow tended to decrease in the MSA-C patients compared with the CCA patients, suggesting that this particular CSF flow analysis may be a new surrogate marker for differentiating both types of cerebellar ataxia.

DOI： 10.2169/internalmedicine.54.4747

Telmisartan Ameliorates Inflammatory Responses in SHR-SR after tMCAO 査読

Kota Sato, Toru Yamashita, Tomoko Kurata, Yusuke Fukui, Nozomi Hishikawa, Kentaro Deguchi, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 ( 10 ) 2511 - 2519 2014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：ELSEVIER SCIENCE BV

Telmisartan, an angiotensin receptor blocker with high lipid solubility, also called metabo-sartan, not only reduces blood pressure (BP), but also ameliorates inflammation in the cerebral cortex and in adipose tissue. We examined the effects of telmisartan on inflammatory responses of monocyte chemotactic protein-1, tumor necrosis factor-a, and ionized calcium-binding adapter molecule 1 in the brain of spontaneously hypertensive rat stroke-resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO). At 12 weeks of age, SHR-SR received tMCAO for 90 minutes and were divided into 3 groups, that is, the vehicle group, a low-dose telmisartan group (.3 mg/kg/day), and a high-dose telmisartan group (3 mg/kg/day). Immunohistological analysis was performed when rats became 6, 12 and 18 months old. Monocyte chemotactic protein-1, tumor necrosis factor-alpha, and ionized calcium-binding adapter molecule 1 cells (/mm(2)) immunoreactivities increased with age in the cerebral cortex and hippocampus of the vehicle group, suggesting strong and persistent inflammatory changes in SHR-SR after tMCAO up to 18 months of age. On the other hand, a low dose of telmisartan significantly reduced such inflammatory changes without lowering BP, whereas a high dose of telmisartan showed a few additional improvements, including the lowering of BP throughout 6-18 months of age. The present study suggests that persistent hypertension after tMCAO caused a long-lasting inflammatory response in the SHR-SR brain, and that even a low dose of telmisartan reduced continuous inflammation without lowering BP via its pleiotropic effects in the SHR-SR brain. A high dose of telmisartan had a few additional benefits, including lowering BP.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.02.019

Long-term Amelioration of Telmisartan on Metabolic Syndrome-related Molecules in Stroke-resistant Spontaneously Hypertensive Rat after Transient Middle Cerebral Artery Occlusion 査読

Kentaro Deguchi, Tomoko Kurata, Yusuke Fukui, Wentao Liu, Zhai Yun, Yoshio Omote, Kota Sato, Syoichiro Kono, Nozomi Hishikawa, Toru Yamashita, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 ( 10 ) 2646 - 2653 2014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：ELSEVIER SCIENCE BV

Telmisartan is expected to ameliorate not only hypertension, but also metabolic syndrome as a metabosartan. We examined the effects of telmisartan on metabolic syndrome-related molecules such as insulin receptor (IR), peroxisome proliferator-activated receptor gamma (PPAR-gamma), and angiotensin 2 type 1 receptor (AT1R) in stroke-resistant spontaneously hypertensive rat (SHR-SR) after transient middle cerebral artery occlusion (tMCAO), by administering telmisartan at either 0 (vehicle), .3 mg/kg/day (low dose), or 3 mg/kg/day (high dose), postoperatively, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months of age. Compared with the vehicle group, the 2 telmisartan groups dose dependently decreased the number of IR-and AT1R-positive neurons in the cerebral cortex in the ipsilateral cerebral cortex from 6 to 18 months after tMCAO. On the other hand, the number of PPAR-gamma-positive neurons increased in a dose-dependent manner in the 2 telmisartan groups from 6 to 18 months. The present study suggests that telmisartan dose-dependently ameliorated metabolic syndrome-related changes in the poststroke brain of SHR-SR with a direct protective effect (low dose) and an additive benefit, an antihypertensive effect at a high dose, for long-term protection after tMCAO.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.06.012

Strong Reduction of Low-Density Lipoprotein Receptor/Apolipoprotein E Expressions by Telmisartan in Cerebral Cortex and Hippocampus of Stroke Resistant Spontaneously Hypertensive Rats 査読

Yun Zhai, Toru Yamashita, Tomoko Kurata, Yusuke Fukui, Kota Sato, Syoichiro Kono, Wentao Liu, Yoshio Omote, Nozomi Hishikawa, Kentaro Deguchi, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 ( 9 ) 2350 - 2361 2014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：ELSEVIER SCIENCE BV

Background: Telmisartan is a unique angiotensin II type 1 receptor blocker with a partial peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonistic property to exert not only antihypertensive effect but also antimetabolic syndrome effect. Methods: We examined the long-term effect of telmisartan on cholesterol transport-related proteins (low-density lipoprotein receptor [LDL-R]/apolipoprotein E [ApoE]) and microtubule-associated proteins 2 (MAP2) in the brains of stroke resistant spontaneously hypertensive rats (SHR-SRs), which were divided into 3 experiment groups including vehicle group (SHR/Ve), low-dose telmisartan group (SHR/Low, 3 mg/kg/day), and high-dose telmisartan group (SHR/High, 3 mg/kg/day). Results: The numbers of LDL-R-and immuno-ApoE-positive neurons increased in both cerebral cortex and hippocampus of SHR/Ve throughout 6, 12, and 18 months of age, compared with age-matched normotensive Wistar rats. On the other hand, telmisartan significantly reduced the numbers of LDL-R-and ApoE immuno-positive neurons in both cerebral cortex and hippocampus, with similar effectiveness in the SHR/Low group without blood pressure (BP) lowering to BP lowering (SHR/High). The decrease of MAP2-positive neuron in SHR/Ve was recovered by telmisartan in both cerebral cortex and hippocampus. Conclusions: These findings suggest that a long-term treatment with telmisartan directly improved neuronal lipid metabolism in the cerebral cortex and hippocampus of SHR-SR, mainly improving LDL-R and ApoE metabolism (SHR/Low) with a small additive benefit by BP lowering (SHR/High), which could provide a preventative approach in patients with hypertension at risk of Alzheimer disease.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.05.033

Protective Effect of Telmisartan Against Progressive Oxidative Brain Damage and Synuclein Phosphorylation in SHR-SR 査読

Yusuke Fukui, Nozomi Hishikawa, Tomoko Kurata, Kota Sato, Toru Yamashita, Kentaro Deguchi, Koji Abe

CEREBROVASCULAR DISEASES 38 84 - 84 2014年9月

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