Faculty Profiles - YAMASHITA Toru

Papers - YAMASHITA Toru

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Two young stroke patients associated with regular intravenous immunoglobulin (IVIg) therapy. Reviewed International journal

Yumiko Nakano, Takeshi Hayashi, Kentaro Deguchi, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Yoshiki Takao, Tomohiro Morio, Koji Abe

Journal of the neurological sciences 361 9 - 12 2016.2

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

We recently experienced 2 young adult patients who developed ischemic stroke after regular intravenous immunoglobulin (IVIg) therapy for agammaglobulinemia with diagnosis of common variable immunodeficiency (CVID) in their childhood. Patient 1 was 26-year-old woman, who developed Wallenberg's syndrome 6 days after the last IVIg therapy, but had no further stroke recurrence with cilostazol later. Patient 2 was 37-year-old man, who developed recurrent cerebral infarction in the territory of bilateral lenticulostriate branches like branch atheromatous disease (BAD) several days after the IVIg therapy. However, he had no further stroke recurrence after bone marrow transplantation (BMT) therapy for his lymphoproliferative disorder. It was suggested that IVIg therapy was associated to these different types of ischemic stroke in our 2 young adult patients with minimal vascular risk factors. Although IVIg therapy is widely used as a relatively safe medication for immunodeficiency disorders or autoimmune diseases, we need to pay more attention to stroke occurrence with regular IVIg therapy.

DOI： 10.1016/j.jns.2015.12.001

Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome Reviewed

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

European Journal of Neurology 23 ( 2 ) 339 - 345 2016.2

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

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. Click here to view the accompanying paper in this issue.

DOI： 10.1111/ene.12845

Combination benefit of cognitive rehabilitation plus donepezil for Alzheimer's disease patients. Reviewed

Kosuke Matsuzono, Nozomi Hishikawa, Yoshiki Takao, Yosuke Wakutani, Toru Yamashita, Kentaro Deguchi, Koji Abe

Geriatrics & gerontology international 16 ( 2 ) 200 - 4 2016.2

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

OBJECTS: Alzheimer's disease (AD) is one of the most important diseases in aging society, and non-drug therapy might be an alternative therapeutic approach. Thus, we evaluated the add-on effect of cognitive rehabilitation on AD patients under donepezil treatment. METHODS: We retrospectively analyzed 55 AD patients with a Mini-Mental State Examination score of 15-25, dividing them into two groups depending on whether they were receiving ambulatory cognitive rehabilitation (group D + R, n = 32) or not (group D, n = 23) in Kurashiki Heisei Hospital over 1 year. The present cognitive rehabilitation included physical therapy, occupational therapy and speech therapy for 1-2 h once or twice a week. RESULTS: Between group D and group D + R, there was no significant difference in baseline data, such as age, Mini-Mental State Examination score, periventricular hyperintensity on magnetic resonance imaging, deep white matter hyperintensity on magnetic resonance imaging or donepezil dose (4.1 mg/day). At 1 year later, however, the Mini-Mental State Examination score improved only in group D + R from 21.7 to 24.0 (**P < 0.001), whereas that of group D remained at 21.5 with both groups of donepezil 5.0 mg/day. CONCLUSION: The combination of cognitive rehabilitation plus a choline esterase inhibitor donepezil showed a better effect for the cognitive function of AD patients than drug only therapy at 1 year.

DOI： 10.1111/ggi.12455

'PrP systemic deposition disease': Clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178 Reviewed

K. Matsuzono, H. Honda, K. Sato, R. Morihara, K. Deguchi, N. Hishikawa, T. Yamashita, S. Kono, Y. Ohta, T. Iwaki, K. Abe

European Journal of Neurology 23 ( 1 ) 196 - 200 2016.1

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

Background and purpose: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. Methods: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). Results: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. Conclusion: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.

DOI： 10.1111/ene.12905

Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy. Reviewed International journal

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

Journal of neurology 263 ( 1 ) 61 - 7 2016.1

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

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 ± 8.1 years old, mean ± SD) and age- and gender-matched 15 CCA patients (63.0 ± 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.

Recent Progress in Therapeutic Strategies for Ischemic Stroke. Reviewed International journal

Toru Yamashita, Koji Abe

Cell transplantation 25 ( 5 ) 893 - 8 2016

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

Possible strategies for treating stroke include neuroprotection in the acute phase of cerebral ischemia and stem cell therapy in the chronic phase of cerebral ischemia. Previously, we have studied the temporal and spatial expression patterns of c-fos, hypoxia inducible factor-1α (HIF-1α), heat shock protein 70 (HSP70), and annexin V after 90 min of transient middle cerebral occlusion in rats and concluded that there is a time window for neuroprotection from 12 to 48 h after ischemia. In addition, we have estimated the neuroprotective effect of glial cell line-derived neurotrophic factor (GDNF) by injecting Sendai viral vector containing the GDNF gene into the postischemic brain. This Sendai virus-mediated gene transfer of GDNF showed a significant neuroprotective effect in the ischemic brain. Additionally, we have administered GDNF and hepatocyte growth factor (HGF) protein into the postischemic rat brain and estimated the infarct size and antiapoptotic and antiautophagic effects. GDNF and HGF significantly reduced infarct size, the number of microtubule-associated protein 1 light chain 3 (LC3)-positive cells, and the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL)-positive cells, indicating that GDNF and HGF were greatly associated with not only the antiapoptotic effect but also the antiautophagic effects. Finally, we have previously transplanted undifferentiated iPSCs into the ipsilateral striatum and cortex at 24 h after cerebral ischemia. Histological analysis was performed at 14 and 28 days after cell transplantation, and we found that iPSCs could supply a great number of doublecortin-positive neuroblasts but also formed tridermal teratoma in the ischemic brain. Our results suggest that iPSCs have a potential to provide neural cells after ischemic brain injury if tumorigenesis is properly controlled. In the future, we will combine these strategies to develop more effective therapies for the treatment of strokes.

DOI： 10.3727/096368916X690548

Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson's Disease with Dementia and Dementia with Lewy Bodies. Reviewed International journal

Mami Takemoto, Kota Sato, Noriko Hatanaka, Toru Yamashita, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe

Journal of Alzheimer's disease : JAD 52 ( 1 ) 205 - 11 2016

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

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in "orientation to place" tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients' lower average scores for "repetition" (MMSE), "recent memory" (HDS-R), and "lexical fluency" (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients' poorer average subscale scores of "orientation to place" (MMSE) and "similarities", "conflicting instructions", and "go-no go" (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD.

DOI： 10.3233/JAD-150952

Comparative Gait Analysis in Progressive Supranuclear Palsy and Parkinson's Disease. Reviewed International journal

Noriko Hatanaka, Kota Sato, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

European neurology 75 ( 5-6 ) 282 - 9 2016

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

BACKGROUND: Although changes to gait are an important clinical feature of progressive supranuclear palsy (PSP), systematic analyses have not been well examined, especially in comparison to Parkinson's disease (PD). METHODS: The characteristics of gait in 20 PSP patients (14 males and 6 females) were evaluated in comparison to 124 PD patients (64 males and 60 females) and 24 controls, that is, healthy age-matched adults (5 males and 19 females). Gait in patients was recorded in a 10-m walking test at a self-selected speed. During this time, patients felt most comfortable while wearing a new portable triaxial accelerometer rhythmogram device. Gait variables among the 3 groups were compared. RESULTS: Both PSP and PD patients shared the following similar hypokinetic gait characteristics: decreased velocity, step length, cadence and mean acceleration. Step time and variability in step time were mutually related. However, among the 3 groups, PSP patients showed characteristically low vertical displacement and a higher acceleration than PD patients at the same cadence. CONCLUSION: Although PSP and PD patients showed similar hypokinetic gait, a reduced vertical displacement characterized walking in PSP patients, differing substantially from the characteristics of walking displayed by PD patients.

DOI： 10.1159/000445111

Recent Progress in Cell Reprogramming Technology for Cell Transplantation Therapy. Reviewed

Toru Yamashita, Koji Abe

Neurologia medico-chirurgica 56 ( 3 ) 97 - 101 2016

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

The discovery of induced pluripotent stem (iPS) cells opened the gate for reprogramming technology with which we can change the cell fate through overexpression of master transcriptional factors. Now we can prepare various kinds of neuronal cells directly induced from somatic cells. It has been reported that overexpression of a neuron-specific transcriptional factors might change the cell fate of endogenous astroglia to neuronal cells in vivo. In addition, some research groups demonstrated that chemical compound can induce chemical-induced neuronal cells, without transcriptional factors overexpression. In this review, we briefly review recent progress in the induced neuronal (iN) cells, and discuss the possibility of application for cell transplantation therapy.

DOI： 10.2176/nmc.ra.2015-0309

Characteristics of audiogram configuration in multiple-system atrophy C and cortical cerebellar atrophy Reviewed International journal

Ryotaro Omichi, Yukihide Maeda, Akiko Sugaya, Yuko Kataoka, Shin Kariya, Rie Nagayasu, Atsuko Nakagawa, Toru Yamashita, Koji Abe, Kazunori Nishizaki

ACTA OTO-LARYNGOLOGICA 136 ( 3 ) 266 - 270 2016

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

CONCLUSION: The prevalence of low-tone hearing loss (LTHL) is significantly high in spinocerebellar degeneration (SCD) with cerebellar predominance, including multiple-system atrophy C (MSA-C) and cortical cerebellar atrophy (CCA). OBJECTIVE: This study aimed to test the hypothesis that SCD with cerebellar predominance, MSA-C and CCA may cause auditory symptoms. METHODS: The shape and threshold of pure-tone audiograms were evaluated for MSA-C (n = 47; mean (± SD) age, 61.6 ± 8.9 years), CCA (n = 16; 62.8 ± 9.5 years), and age-matched controls (n = 169; 62.5 ± 10.7 years). To differentiate specific hearing loss for MSA-C and CCA from presbycusis, the shape of audiograms was examined based on previously established audiological criteria. RESULTS: When audiogram shape was defined according to audiological criteria, the odds ratio for LTHL in SCD compared to controls was 2.492 (95% confidence interval (CI) = 1.208-5.139; p < 0.05, Pearson's Chi-square test) in MSA-C and 2.194 (95% CI = 0.709-6.795) in CCA. When the selection of audiogram shape according to these criteria was verified by three certified audiologists, odds ratios for LTHL in MSA-C and CCA were 3.243 (95% CI = 1.320-7.969) and 3.692 (95% CI = 1.052-12.957), respectively, significantly higher than in controls.

DOI： 10.3109/00016489.2015.1104722

Prospective surveillance data of human prion disease in the Chugoku and Shikoku regions of Japan

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

PRION 10 S90 - S91 2016

Differentiating progressive supranuclear palsy from Parkinson's disease by MRI-based dynamic cerebrospinal fluid flow. Reviewed International journal

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 2015.10

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

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

Cognitive and affective functions of aged subacute myelooptico neuropathy patients in Japan

Yuko Kawahara, Kentaro Deguchi, Nozomi Hishikawa, Tomoko Kurata, Kota Sato, Syoichiro Kono, Yoshio Omote, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 3 ( 5 ) 173 - 178 2015.9

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

Background: Subacute myelo-optico neuropathy was the first epidemic drug intoxication that affected many people in Japan in the 1970s. Aim: More than 40 years later, we assessed the real conditions of subacute myelooptico neuropathy patients. Methods: The present study examined current cognitive and affective functions, activities of daily living, and vascular endothelial function in aged subacute myelooptico neuropathy patients (n = 28) compared with age-,sex-,body mass indexand years of schooling-matched normal controls (n = 141).Results: Mini-Mental State Examination, Hasegawa Dementia Scale-Revised, Montreal Cognitive Assessment and Frontal Assessment Battery scores were not significantly lower in subacute myelo-optico neuropathy patients, but the Geriatric Depression Scale was significantly higher without apathy. Computerized touchpanel tests showed poor performance in the flipping cards game, arranging pictures game and beating devils game, whereas activities of daily living and vascular endothelial function were within normal limits.Conclusion: The present study shows that subacute myelo-optico neuropathy patients showed essentially normal cognitive function using standard cognitive assessments, although the touch- panel tests detected some decline in subacute myelo- optico neuropathy patients. Subacute myelo- optico neuropathy patients presented a higher depression score without evident apathy, activities of daily living decline or vascular endothelial dysfunction.

DOI： 10.1111/ncn3.12000

Polyneuritis and refractory headache overlap with synovitis, acne, pustulosis, hyperostosis and osteitis syndrome

Kosuke Matsuzono, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 3 ( 5 ) 182 - 184 2015.9

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

The primary clinical manifestations of synovitis, acne, pustulosis, hyperostosis and osteitis syndrome are skin lesions and osteitis. We describe a 53-year-old woman patient suffering from overlapping refractory headache and polyneuritis (cranial nerves I, II and VII). She complained of headaches, which recurred every month, followed by bilateral anosmia and left vision loss approximately 1 year later. Prednisolone therapy improved her symptoms; however, her refractory headache, pain in the right shoulder and left hip joint, and rash recurred 1 year after prednisolone withdrawal. Also, the patient presented with left sensorineural deafness and extensive acne on her body, and bone scintigraphy and bone biopsy showed synovitis, acne, pustulosis, hyperostosis and osteitis syndrome. After treatment, her symptoms improved without recurrence. Although synovitis, acne, pustulosis, hyperostosis and osteitis syndrome induced by polyneuritis is rare, it should be considered when clinicians encounter patients presenting with headache and polyneuritis of unknown cause.

DOI： 10.1111/ncn3.171

Aggressive Garcin's syndrome by acquired cystic disease of kidney-related renal cell carcinoma in a long-term hemodialytic patient. Reviewed International journal

Yuko Kawahara, Kentaro Deguchi, Kota Sato, Nozomi Hishikawa, Syoichiro Kono, Yasuyuki Ohta, Toru Yamashita, Eiko Hayashi, Yasuharu Sato, Koji Abe

Journal of the neurological sciences 355 ( 1-2 ) 216 - 8 2015.8

Cerebrospinal blood flow and its regulation Reviewed

Toru Yamashita, Kazunori Miyazaki, Koji Abe

Neuroanesthesia and Cerebrospinal Protection 25 - 29 2015.8

Language：English Publishing type：Part of collection (book) Publisher：Springer Japan

The human brain utilizes large amounts of O2, which means that the rate of blood flow has to be maintained at a consistently high level. This is made possible by "cerebral autoregulation," the process by which the cerebral and spinal blood vessels keep cerebral blood flow constant, even under change in systemic blood pressure. In addition, cerebral and spinal blood flow and its regulation appear to be closely related not only to vascular disease phenotype but also the pathophysiology of various neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. In this review, we briefly highlight cerebral and spinal blood flow and its autoregulation and show its relationship to neurological diseases.

DOI： 10.1007/978-4-431-54490-6_2

High Incidence of Dementia Conversion than Stroke Recurrence in Poststroke Patients of Late Elder Society. Reviewed International journal

Yumiko Nakano, Kentaro Deguchi, Toru Yamashita, Ryuta Morihara, Kosuke Matsuzono, Yuko Kawahara, Kota Sato, Syoichiro Kono, Nozomi Hishikawa, Yasuyuki Ohta, Yasuto Higashi, Yoshiki Takao, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 24 ( 7 ) 1621 - 8 2015.7

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

BACKGROUND: This study investigated the incidence of current poststroke dementia (PSD), the annual conversion ratio into PSD, and the risk factors for conversion. METHODS: In a 4.8-year follow-up period, 112 poststroke patients (ischemic stroke and intracerebral hemorrhage) were retrospectively investigated in cognitive examinations. They were categorized into 3 subgroups: converters into PSD, nonconverters who maintained their normal cognitive functions, and reverters who recovered to the normal mentality range. The clinical and demographic characteristics of these 3 subgroups were analyzed. RESULTS: Among all 112 poststroke patients (61.6% male, 73.6 ± 10.4 years old), 16.1% had PSD. During the follow-up period, a part of the normal baseline mentality group (83.9% of 112 original patients) newly developed PSD (subdivided into converters) with an annual conversion rate of 7.6%. The reversion rate from the baseline PSD group was 11.3%. There were significant differences in age (P < .05), baseline mini-mental state examination scores (P < .05), body mass index (P < .05), and periventricular and deep white matter hyperintensity grades (P < .05 and P = .01, respectively) between converters and nonconverters. The annual rate of stroke recurrence was only 2.2% in all stroke subtypes. CONCLUSIONS: In comparison with stroke recurrence (2.2%), 7.6% of the annual PSD conversion rate was very high. Therefore, prevention of direct conversion into PSD without stroke recurrence may be another important aspect of poststroke clinics, especially in late elder society.

DOI： 10.1016/j.jstrokecerebrovasdis.2015.03.037

Protective effect of telmisartan on neurovascular unit and inflammasome in stroke-resistant spontaneously hypertensive rats. Reviewed International journal

Wentao Liu, Toru Yamashita, Tomoko Kurata, Syoichiro Kono, Nozomi Hishikawa, Kentaro Deguchi, Yun Zhai, Koji Abe

Neurological research 37 ( 6 ) 491 - 501 2015.6

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

OBJECTIVES: Hypertension is a crucial risk factor for both stroke and dementia, including Alzheimer's disease (AD). We inspected the effect of telmisartan on the neurovascular unit (NVU) and related inflammatory responses in spontaneously hypertensive rat stroke resistant (SHR-SR) by observing the components of NVU such as N-acetyl glucosamine oligomer (NAGO), collagen IV, astrocytes, and matrix metalloproteinase-9 (MMP-9), as well as inflammasome NOD-like receptors family protein 3 (NLRP3). METHODS: In the present study, we examined the effect of a highly selective angiotensin type 1 (AT-1) antagonist of angiotensin 2 receptor with high lipid solubility, telmisartan, on NVU and related inflammatory responses in SHR-SR with a low dose (0.3 mg/kg/day) only for improving metabolic syndrome, and a high dose (3 mg/kg/day) for improving both metabolic syndrome and SHR-SR hypertension. RESULTS: Compared to normotensive Wistar rats, long-lasting hypertension in SHR-SR disrupted NVU by changing immunohistological components such as NAGO, collagen IV, astrocytes, and MMP-9. SHR-SR also strongly induced AD-related inflammasome NLRP3 in neuronal cells with age. However, such NVU disruption and inflammasome activation were greatly improved with dose-dependent telmisartan treatments. DISCUSSION: These results suggest that telmisartan comprehensively protected the NVU components by reducing inflammatory reactions relative to AD in hypertensive rats, which could also preclude the risk of AD under hypertension.

DOI： 10.1179/1743132815Y.0000000002

Simultaneous assessment of cognitive and affective functions in multiple system atrophy and cortical cerebellar atrophy in relation to computerized touch-panel screening tests. Reviewed International journal

Yuko Kawahara, Yoshio Ikeda, Kentaro Deguchi, Tomoko Kurata, Nozomi Hishikawa, Kota Sato, Syoichiro Kono, Taijun Yunoki, Yoshio Omote, Toru Yamashita, Koji Abe

Journal of the neurological sciences 351 ( 1-2 ) 24 - 30 2015.4

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

Cognitive impairment and affective dysfunction of multiple system atrophy (MSA) and cortical cerebellar atrophy (CCA) have not been simultaneously examined comparing standard test batteries and a sensitive tool to detect subtle cognitive decline in patients. In the present study, we simultaneously examined cognitive and affective ability in MSA with predominant cerebellar ataxia (MSA-C, n=25), MSA with predominant parkinsonism (MSA-P, n=8), and CCA (n=14) patients using computerized touch panel screening tests. Mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), frontal assessment battery (FAB), and Montreal cognitive assessment (MoCA) scores were significantly lower in MSA-C patients than in age-and gender-matched normal controls. One MSA-C patient showed a decrease in the regional cerebral blood flow (rCBF) of the frontal lobe. MSA-P patients showed no such cognitive decline. Only FAB and MoCA scores were significantly lower in the CCA patients. MSA and CCA patients also showed a mild to moderate depressive state. Touch-panel screening tests demonstrated a significant decline of beating devils game in all three disease groups including MSA-P patients, and a significant extension of the flipping cards game only in MSA-C patients. The present study demonstrated different cognitive and affective functions among MSA-C, MSA-P, and CCA patients, and a sensitive screening method for cognitive assessment using touch-panel tests.

DOI： 10.1016/j.jns.2015.02.010

Long-term effect of telmisartan on Alzheimer's amyloid genesis in SHR-SR after tMCAO. Reviewed International journal

Tomoko Kurata, Violeta Lukic, Miki Kozuki, Daisuke Wada, Kazunori Miyazaki, Nobutoshi Morimoto, Yasuyuki Ohta, Kentaro Deguchi, Toru Yamashita, Nozomi Hishikawa, Kosuke Matsuzono, Yoshio Ikeda, Tatsushi Kamiya, Koji Abe

Translational stroke research 6 ( 2 ) 107 - 15 2015.4

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

Telmisartan is expected to reduce not only the level of blood pressure but also neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan. We examined the effects of telmisartan on Alzheimer's disease (AD) pathology in spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle), 0.3 mg/kg/day (low dose, with no reduction of blood pressure), or 3 mg/kg/day (high dose, with a significant reduction of blood pressure) p.o. from 3 months (M) of age, and performed immunohistological analysis at 6, 12, and 18 M of age. The numbers of amyloid β (Aβ)-positive neurons in the cerebral cortex and hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex progressively increased with age until 18 M in the SHR-SR after tMCAO. On the other hand, low-dose telmisartan significantly reduced the number of Aβ-positive neuron as well as SP at 6, 12, and 18 M. High-dose telmisartan showed further reductions of the above AD pathology. The present study suggests that telmisartan reduced both intracellular Aβ and extracellular SP accumulations after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a strong effect of telmisartan could provide a preventative approach for AD in post-stroke patients with hypertension.

DOI： 10.1007/s12975-013-0321-y

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