Publications (15)49.3 Total impact
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Article: Association of Physical Activity with the Visuospatial/Executive Functions of the Montreal Cognitive Assessment in Patients with Vascular Cognitive Impairment.
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ABSTRACT: BACKGROUND: The Montreal Cognitive Assessment (MoCA) is more suitable than the Mini-Mental State Examination (MMSE) for the detection of vascular cognitive impairment. In this study, we performed a correlation analysis of MoCA/MMSE scores with daily physical activity in patients with subcortical ischemic white matter changes. METHODS: Ten patients (average 75.9 ± 9.1 years old) with extensive leukoaraiosis detected on magnetic resonance imaging underwent cognitive testing, including the MMSE and the Japanese version of the MoCA (MoCA-J). Physical activity was monitored with the Kenz Lifecorder EX device (Suzuken, Nagoya, Japan) to assess daily physical activity in terms of caloric expenditure, motor activity, number of steps, and walking distance for 6 months. Correlations of individual physical activity with total and subscale scores of MMSE/MoCA-J or 6-month interval change of MoCA-J scores were assessed. RESULTS: The total or subscale scores of the MMSE did not correlate with any parameters of physical activity. However, the mean number of steps and walking distance significantly correlated with the total MoCA-J scores (r = .67 and .64, respectively) and its visuospatial/executive subscores (r = .66 and .66, respectively). The mean interval change of MoCA-J was + .6; those who improved number of steps (n = 4; 80.5 ± 3.0 years of age) had significantly preserved MoCA-J scores compared to those who did not (n = 6; 73.0 ± 11.6 years of age; +2.0 versus - .3; P = .016). CONCLUSIONS: These results suggest that MoCA is useful to detect a biologically determined specific relationship between physical activity and executive function. In addition, physical exercise, such as walking, may help enhance cognitive function in patients with vascular cognitive impairment of subcortical origin.Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 11/2012; -
Article: Suitability of the Montreal Cognitive Assessment versus the Mini-Mental State Examination in Detecting Vascular Cognitive Impairment.
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ABSTRACT: The Mini-Mental State Examination (MMSE) has been criticized as being an insufficient screening test for patients with vascular cognitive impairment because of its insensitivity to visuospatial and executive functional deficits. The Montreal Cognitive Assessment (MoCA) was designed to be more sensitive to such deficits, and thus may be a superior screening instrument for vascular cognitive impairment. Twelve patients with extensive leukoaraiosis detected on magnetic resonance imaging (average age, 76.0 ± 8.7 years) underwent neurologic and cognitive testing, including MMSE and the Japanese version of the MoCA (MoCA-J). Accepted cutoff scores of <27 for the MMSE and <26 for the MoCA-J were taken to indicate cognitive impairment. Z-scores were calculated to evaluate the discriminating ability of individual MMSE and MoCA-J subtest scores. Although there was a strong correlation between the total MMSE and total MoCA-J scores (r = 0.90; P < .0001), MMSE scores were skewed toward the higher end of the range (range, 18-30; median, 28), whereas MoCA-J scores were normally distributed (range, 9-28; median, 21). Of the 7 patients with an unimpaired MMSE score, 6 (86%) had an impaired MoCA-J score. Z-scores were >5 for 4 MMSE subtests (orientation, registration, naming, and language) but for only 1 MoCA-J subtest (naming). The MoCA-J better discriminated cognitive status in subjects with extensive leukoaraiosis. Our findings suggest that the MoCA-J is more sensitive than the MMSE in screening for cognitive impairment in patients with subcortical vascular cognitive impairment.Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 02/2012; -
Article: [Case report of transthyretin Val30Met familial amyloid polyneuropathy presenting hydrocephalus].
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ABSTRACT: A 70-year-old man was admitted to our hospital with visual loss, dysesthesia, gait disturbance, and urinary retention. A pacemaker was implanted 1 year ago for atrioventricular conduction block. Neurologic examination revealed mild cognitive impairment, near blindness with vitreous opacity, diffuse muscle weakness, loss of all sensory modalities with areflexia, and orthostatic hypotension. Head CT showed hydrocephalus. The Congo red staining of vitrectomized specimen and the biopsied sural nerve showed amyloid depositions. Gene analysis disclosed Val30Met missense mutation of transthyretin, which is responsible for familial amyloid polyneuropathy. His bed-ridden brother also had severe urinary dysfunction and orthostatic hypotension with hydrocephalus on MRI. These two sibling cases suggest correlation of the transthyretin Val30Met mutation with hydrocephalus, a rare phenotype of this disease.Rinshō shinkeigaku = Clinical neurology. 01/2012; 52(4):257-60. -
Article: Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts.
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ABSTRACT: Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer's disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer's disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm(2) in mild, 0.584/cm(2) in moderate, and 4.370/cm(2) in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid β (Aβ) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aβ depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aβ accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs.Acta Neuropathologica 12/2011; 123(3):381-94. · 9.32 Impact Factor -
Article: Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia.
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ABSTRACT: The Cilostazol Stroke Prevention Study II has shown a similar efficacy in stroke prevention but markedly fewer hemorrhagic events with the phosphodiesterase inhibitor cilostazol versus aspirin. The purpose of this study is therefore to investigate how cilostazol affects cerebral hemodynamics and whether it prevents hemorrhagic transformation induced by recombinant tissue plasminogen activator (rtPA) in a mouse model of focal ischemia/reperfusion. Particular emphasis will be placed on the plasma-microvessel interface. After receiving food containing 0.3% cilostazol or standard food for 7 days, adult C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion with or without rtPA (10mg/kg) intravenously administered prior to reperfusion. Cerebral blood flow was monitored at several time points by laser speckle imaging in the 24 hour period post reperfusion, before neurobehavioral and histological assessment. The long-term effect of cilostazol on cerebral ischemia was analyzed in the non-rtPA cohort. In the non-rtPA cohort, pretreatment by cilostazol significantly decreased the endothelial expression of adhesion molecules (P-selectin and intercellular adhesion molecule-1) and prevented platelet aggregation and leukocyte plugging in the microvessels after cerebral ischemia/reperfusion in the acute phase. Cilostazol significantly reduced mortality rate and improved motor function at 7 days post-ischemia/reperfusion. In the rtPA cohort, cilostazol significantly suppressed edema formation and hemorrhagic transformation with reduced density of microglial cells positive for matrix metalloproteinase-9 in the cerebral cortex and the striatum. In both cohorts, cilostazol significantly suppressed focal no-reflow, mitigated cerebral infarct, and improved neurological outcome. Cilostazol may possess protective properties against cerebral ischemic injury by preventing no-reflow and hemorrhagic transformation, via maintenance of microvascular integrity.Experimental Neurology 12/2011; 233(1):523-33. · 4.70 Impact Factor -
Article: Selective white matter abnormalities in a novel rat model of vascular dementia.
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ABSTRACT: Rats subjected to bilateral common carotid artery (CCA) occlusion or 2-vessel occlusion (2VO) have been used as animal models of subcortical ischemic vascular dementia. However, this model possesses an inherent limitation in that cerebral blood flow (CBF) drops too sharply and substantially after ligation of CCAs. To circumvent such hypoxic-ischemic conditions, we tested implantation of the ameroid constrictor device on bilateral CCAs of male Wistar-Kyoto rats and more precisely replicated chronic cerebral hypoperfusion by gradual narrowing of the CCAs (2-vessel gradual occlusion; 2VGO). The acute cerebral blood flow reduction and resultant inflammatory responses observed in the 2VO rats were eliminated in the 2VGO rats. Thus, chronic cerebral hypoperfusion was segregated, and induced selective white matter changes with relatively preserved neurovascular coupling and substantially less metabolic and histological derangements in the gray matter including the hippocampus. This led to significant spatial working memory impairment of a magnitude similar to the 2VO rats at 28 days postoperation. The 2VGO model may more closely mimic cognitive impairment subsequent to selective white matter damage.Neurobiology of aging 11/2011; 33(5):1012.e25-35. · 5.94 Impact Factor -
Article: Clinicopathologic study on an ALS family with a heterozygous E478G optineurin mutation.
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ABSTRACT: We investigated a family manifesting amyotrophic lateral sclerosis (ALS) with a heterozygous E478G mutation in the optineurin (OPTN) gene. Clinically, slow deterioration of motor function, mood and personality changes, temporal lobe atrophy on neuroimaging, and bizarre finger deformity were noted. Neuropathologically, TAR DNA-binding protein 43 (TDP-43)-positive neuronal intracytoplasmic inclusions were observed in the spinal and medullary motor neurons. In these cells, the immunoreactivity of nuclear TDP-43 was reduced. Consecutive sections revealed that the inclusions were also reactive with anti-ubiquitin and anti-p62 antibodies, but noticeably negative for OPTN. In addition, TDP-43/p62-positive glial cytoplasmic inclusions (GCIs) were scattered throughout the spinal cord and the medullary motor nuclei. Furthermore, Golgi fragmentation was identified in 70% of the anterior horn cells (AHCs). The presence of AHCs with preserved nuclear TDP-43 and a fragmented Golgi apparatus, which are unrecognizable in sporadic ALS, indicates that patients with the E4787G OPTN mutation would manifest Golgi fragmentation before loss of nuclear TDP-43. In the neocortex, GCIs were sparsely scattered among the primary motor and temporal cortices, but no neuronal TDP-43-positive inclusions were detected. In the amygdala and the ambient gyrus, argyrophilic grains and ballooned neurons were seen. The thorough neuropathologic investigations performed in this work demonstrated that OPTN-positive inclusion bodies, if any, were not prominent. We postulate that optineurinopathy is closely linked with TDP-proteinopathy and speculate that this heterozygous E478G mutation would cause ALS by acting through a dominant-negative mechanism.Acta Neuropathologica 06/2011; 122(2):223-9. · 9.32 Impact Factor -
Article: Colocalization of 14-3-3 proteins with SOD1 in Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis cases and the animal model.
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ABSTRACT: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice. We examined the postmortem brains and the spinal cords of three FALS cases (A4V SOD1 mutant). Transgenic mice expressing the G93A mutant human SOD1 (mutant SOD1-Tg mice), transgenic mice expressing the wild-type human SOD1 (wild-type SOD1-Tg mice), and non-Tg wild-type mice were also subjected to the immunohistochemical analysis. In all the FALS patients, LBHIs were observed in the cytoplasm of the anterior horn cells, and these inclusions were immunopositive intensely for pan 14-3-3, 14-3-3β, and 14-3-3γ. In the mutant SOD1-Tg mice, a high degree of immunoreactivity for misfolded SOD1 (C4F6) was observed in the cytoplasm, with an even greater degree of immunoreactivity present in the cytoplasmic aggregates of the anterior horn cells in the lumbar spinal cord. Furthermore, we have found increased 14-3-3β and 14-3-3γ immunoreactivities in the mutant SOD1-Tg mice. Double immunofluorescent staining showed that C4F6 and 14-3-3 proteins were partially co-localized in the spinal cord with FALS and the mutant SOD1-Tg mice. In comparison, the wild-type SOD1-Tg and non-Tg wild-type mice showed no or faint immunoreactivity for C4F6 and 14-3-3 proteins (pan 14-3-3, 14-3-3β, and 14-3-3γ) in any neuronal compartments. These results suggest that 14-3-3 proteins may be associated with the formation of SOD1-containing inclusions, in FALS patients and the mutant SOD1-Tg mice.PLoS ONE 01/2011; 6(5):e20427. · 4.09 Impact Factor -
Article: The influence of chronic cerebral hypoperfusion on cognitive function and amyloid β metabolism in APP overexpressing mice.
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ABSTRACT: Cognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer's disease resulting from a neurodegenerative process. However, it is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer's disease and vascular cognitive impairment. Nevertheless, it still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. Therefore, we investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid β deposition in amyloid precursor protein (APP) overexpressing transgenic mice. Two months old mice overexpressing a mutant form of the human APP bearing both the Swedish and Indiana mutations (APP(Sw/Ind)-Tg mice), or their wild-type littermates, were subjected to chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) using microcoils or sham operation. Barnes maze test performance and histopathological findings were analyzed at eight months old by 2 × 2 factorial experimental designs with four groups. BCAS-operated APP(Sw/Ind)-Tg mice showed significantly impaired learning ability compared to the other three groups of mice. Two-way repeated measures analysis of variance showed a synergistic interaction between the APP genotype and BCAS operation in inducing learning impairment. The cognitive performances were significantly correlated with the neuronal densities. BCAS significantly reduced the density of Nissl-stained neurons and silver-stained cored plaques in the hippocampus of APP(Sw/Ind)-Tg mice but increased the amount of filter-trap amyloid β in the extracellular-enriched soluble brain fraction, compared to those from sham operated mice. The results suggest interaction between chronic cerebral hypoperfusion and APP(Sw/Ind) overexpression in cognitive decline in mice through enhanced neuronal loss and altered amyloid β metabolism.PLoS ONE 01/2011; 6(1):e16567. · 4.09 Impact Factor -
Article: Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy.
Neurology 01/2010; 74(1):93; author reply 93. · 8.31 Impact Factor -
Article: Cortical microinfarcts in Alzheimer's disease and subcortical vascular dementia.
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ABSTRACT: Cortical microinfarcts are reported in Alzheimer's disease, but not in subcortical vascular dementia; the disease specificity of cortical microinfarcts therefore remains unclear. The distribution of cortical microinfarcts in Alzheimer's disease (n = 8) and subcortical vascular dementia (n = 6) was analyzed. Cortical microinfarcts were frequently detected in Alzheimer's disease, whereas they were rarely observed in subcortical vascular dementia. In Alzheimer's disease, cortical microinfarcts were present predominantly in the occipital lobe, the area of predilection for amyloid angiopathy, and also in the vascular borderzone. Cortical microinfarcts were invariably located very close to amyloid beta-deposited vessels with intercellular adhesion molecule-1 expression. These results indicate that cortical microinfarcts are caused by the pathomechanism related to Alzheimer's disease, most likely to amyloid angiopathy.Neuroreport 06/2009; 20(11):990-6. · 1.66 Impact Factor -
Article: [Case of callosal disconnection syndrome with a chief complaint of right-hand disability, despite presence of left-hand diagonistic dyspraxia].
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ABSTRACT: e report the case of 48-year-old right-handed male patient with an infarction affecting most part of the body and the splenium of the left half of the corpus callosum. Neuropsychological examination revealed typical signs of callosal disconnection including left-sided apraxia, diagonistic dyspraxia, left-sided agraphia, left-hand tactile anomia, left hemialexia, and right-sided constructional disability. Moreover, he complained of impairment in activities involving the right hand disability and agraphia. He could not stop behaving with his right hand when he had a vague idea. For example, he involuntarily picked up a tea bottle with his right hand when he had a desire to drink, although the action was not appropriate to that occasion. The imitation and utilization behavior did not imply this case, because his right hand behaviors were not exaggerated in response to external stimuli, such as the gestures of the examiner or the subjects in front of the patient. Unexpectedly, he complained about impairment of the activity of his right hand and was unaware of left hand apraxia or diagonistic dyspraxia; this trend continued for 6 months, at the time of this writing. We argue that the patient may have been subconsciouly aware of the symptoms of his left hand but had not verbalized them.Brain and nerve = Shinkei kenkyū no shinpo 05/2009; 61(4):495-500. -
Article: Leukoencephalopathy with cognitive impairment following tocilizumab for the treatment of rheumatoid arthritis (RA).
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ABSTRACT: The biological agent tocilizumab, is a humanized, anti-human interleukin-6 receptor antibody. A 72-year-old woman developed cognitive impairment during the Phase III clinical trial of tocilizumab for the treatment of rheumatoid arthritis. MRI demonstrated hyperintense dissemination throughout the white matter on T2WI. An initial diagnosis of possible progressive multifocal leukoencephalopathy was made, but the PCR for JC virus DNA was negative in the CSF. The leukoencephalopathy might have been caused by a mechanism related to tocilizumab itself. It is strongly recommended to perform MRI if a patient develops any cognitive impairment during tocilizumab therapy.Internal Medicine 02/2009; 48(15):1307-9. · 0.94 Impact Factor -
Article: Postpartum angiopathy associated with reversible borderzone ischemia.
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ABSTRACT: A 32-year-old woman developed a headache, seizures, and stupor on postpartum day 8. An initial diagnosis of possible encephalitis was made considering the presence of fever, neck stiffness, and abnormal CSF findings. MRI demonstrated hyperintense signals consistent with bilateral borderzone areas. MRA showed severe proximal narrowing of anterior, middle, and posterior cerebral arteries bilaterally. The patient recovered completely over 2 weeks, and repeated MRI and MRA scans were normal. Reversible vasoconstrictions have been known to occur during puerperium, and the clinical symptoms of our patient resembled such cases. Prior reports attributed these cases of postpartum angiopathy to capillary leakage and edema resulting in leukoencephalopathy. Our case suggests reversible borderzone ischemia as an additional pathological process.Internal Medicine 02/2008; 47(4):309-12. · 0.94 Impact Factor -
Article: [A case of meningeal carcinomatosis presenting with bilateral hearing loss].
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ABSTRACT: We report the case of a 63-year-old male who developed rapidly progressive bilateral deafness. Two months later he became stuporous, and was transferred to our hospital. The patient's MRI demonstrated bilateral hypertrophic VII-VIII cranial nerve roots that were well enhanced. Gradually, the patient's condition worsened, and he died on the 12th day after admission. Autopsy revealed meningeal carcinomatosis with poorly differentiated gastric adenocarcinoma. White firm masses of the bilateral seventh and eighth bilateral cranial nerve roots were found at autopsy, which were found to be metastases of the gastric cancer cells as well. Metastatic tumors can be take into consideration as a differential diagnosis for bilateral-enhanced eighth cranial nerve root masses.Brain and nerve = Shinkei kenkyū no shinpo 01/2008; 59(12):1385-9.
Top co-authors
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Institutions
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2012
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National Institute of Biomedical Innovation
Ōsaka-shi, Osaka-fu, Japan
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2009–2011
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Kyoto University
- Department of Neurology
Kyoto, Kyoto-fu, Japan
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