Kenji Nakashima

Tottori University, TTJ, Tottori, Japan

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Publications (382)980.18 Total impact

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    ABSTRACT: We aimed to clarify the longitudinal course of mild parkinsonian signs (MPS) and their association with dementia and functional disability by conducting a comprehensive epidemiological study, including brain MRI, and assessments of cognition, depression, and sleep, in people aged ≥ 65 years living in Ama-cho. We diagnosed MPS and parkinsonism (PS) using a modified Unified Parkinson's Disease Rating Scale. The phase I study was conducted between 2008 and 2010 (n = 729) and the phase II between 2011 and 2013 (n = 436). By phase II, 8.5% of the phase I participants without PS had developed PS. In addition to older age, a lower Mini-Mental State Examination (MMSE) score, and lower body mass index, the MPS rigidity subtype was a significant independent predictor of PS onset. By phase II, 10.1% of the participants without dementia or PS at phase I had developed dementia. Older age, lower MMSE score, and the axial dysfunction and tremor MPS subtypes were significant independent predictors of dementia development. By phase II, 38.8% of participants with MPS at phase I showed no motor symptoms. Younger age and adequate sleep were significant predictors for this reversion. Periventricular and deep white matter hyperintensity Fazekas scores increased with the evolution of parkinsonian signs. MPS is therefore critically, although sometimes reversibly, associated with PS and dementia development in elderly people.
    No preview · Article · Mar 2016

  • No preview · Article · Jan 2016 · Parkinsonism & Related Disorders
  • Satoko Nakashita · Yuki Tajiri · Kenji Wada-Isoe · Kenji Nakashima

    No preview · Article · Jan 2016 · Parkinsonism & Related Disorders
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    ABSTRACT: Aim: An association between body mass index (BMI) and stroke outcome have been reported, but the results are controversial. The aim of the present study was to evaluate whether BMI is associated with ischemic stroke outcome. Methods: Consecutive Japanese acute ischemic stroke patients were analyzed. BMI was categorized as underweight (BMI <18.5 kg/m(2) ), normal weight (18.5-24.9 kg/m(2) ) and obese (≥25 kg/m(2) ). BMI and short-term and long-term outcomes were examined. Short-term outcomes were evaluated using the modified Rankin scale score at hospitalization and discharge; modified Rankin scale ≥3 was defined as a poor outcome. Long-term outcomes were evaluated by all-cause mortality. The recurrence rate was also evaluated in each BMI group. Values of P < 0.05 were considered significant. Results: A total of 1206 acute ischemic stroke patients (760 men; mean age 72.5 years) were analyzed in the present study. There were 111 underweight cases (9.2%), 785 normal weight cases (65.1%) and 310 obese cases (25.7%). The underweight group had a significantly higher rate of poor short and long-term outcomes than the normal weight group. The outcomes of the obese group were not significantly different from those of the normal weight group. Recurrence was not significantly different among the groups. Conclusions: Lower BMI might be a predictor of poorer short-term and long-term stroke outcomes. Geriatr Gerontol Int 2016; ●●: ●●-●●.
    No preview · Article · Jan 2016 · Geriatrics & Gerontology International
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    ABSTRACT: Objective: To classify the patterns of functional decline in patients with sporadic amyotrophic lateral sclerosis (ALS) and explore the genetic backgrounds that modified these patterns. Methods: We included 465 patients with sporadic ALS in the analysis and clustered the longitudinal functional scores in the registered patients, using a mixture approach of a non-linear mixed-effects model. We conducted a genome-wide analysis of 572 983 single nucleotide polymorphisms (SNPs). We then assessed the association between the clusters of longitudinal functional scores and SNPs. Results: We identified the following four clusters of longitudinal functional decline in the cases: a rapid decline cluster, an intermediate decline cluster, a sigmoidal decline cluster and a moderate decline cluster. We identified seven SNPs associated with the rapid decline cluster, using a recessive model (p=3.47-8.34×10(-8)). The OR for the probabilities of the rapid decline cluster ranged from 5.5 to 5.84. Homozygosity for the minor alleles in the seven SNPs, which constituted a linkage disequilibrium (LD) block, was associated with decreased expression of TTN (encoding Titin, a large sarcomere protein) in the expression quantitative trait loci database of a large-scale Japanese genetic variation database (p=8.6×10(-10)-1.1×10(-7)). TTN expression in immortalised lymphocyte lines was decreased in patients who were homozygous for the minor alleles compared with those who were homozygous for the major alleles (n=19 in each group, p=0.002). Conclusions: We detected an LD block associated with a rapid functional decline in patients with sporadic ALS, which is linked to decreased expression of TTN.
    Full-text · Article · Jan 2016 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: Objective Melatonin is effective for treating patients with rapid eye movement sleep behavior disorder (RBD). Ramelteon, a novel hypnotic, acts as a melatonin receptor agonist. In the current study, we investigated the effects of ramelteon on sleep disorders, including RBD, in patients with Parkinson's disease (PD). Methods We evaluated 35 patients from multiple centers with idiopathic PD accompanied by sleep disturbances (age: 69.1±11.1 years; 17 men, 18 women; PD morbidity: 6.9±5.7 years; Hoehn & Yahr stage: 2.5±0.8; levodopa dose equivalent: 561±401 mg/day). The patients received 8 mg of ramelteon before sleep once daily for 12 weeks. Motor and sleep symptoms were evaluated both before and after ramelteon administration. Results Of the 35 patients enrolled in this study, 24 (68.6%) were diagnosed with probable RBD (pRBD) using the Japanese version of the RBD screening questionnaire. Ramelteon administration reduced the severity of sleep disturbances in patients with PD. It also lowered scores on the Japanese version of the RBD questionnaire in patients with PD and pRBD. Conclusion Ramelteon may have beneficial effects on sleep disturbances, especially on RBD in patients with PD.
    Preview · Article · Jan 2016 · Internal Medicine
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by serious muscle atrophy and weakness. The purpose of this study was to find prognostic factors in patients with mild ALS using application forms for the Specified Disease Treatment Research Program in Japan. We classified ALS as mild, moderate and severe. The subjects consisted of 363 patients with mild ALS who underwent needle electromyography at registration and were followed for more than one year. Time to progression to severe ALS and time to deterioration of activities of daily living such as speech dysfunction, upper limb dysfunction, and walking disability were used as outcomes. Cox proportional hazards model analysis was performed to identify prognostic factors. Of the patients with initially mild ALS, 38.3% (139/363) had progressed severe ALS at the last follow-up. In multivariate analysis of time to progression to severe ALS, bulbar onset (hazard ratio [95% confidence interval]: 1.68 [1.13-2.49], p = 0.010), tongue atrophy (1.69 [1.14-2.51], p = 0.009), dyspnea (1.57 [1.02-2.41], p = 0.042) and active denervation findings (ADFs) of the cervical-upper limb area (1.81 [1.25-2.63], p = 0.002) emerged as prognostic factors. Furthermore ADFs in the trunk area were prognostic factors for upper limb dysfunction and walking disability (1.72 [1.05-2.81], p = 0.031, and 1.97 [1.09-3.59], p = 0.026). In conclusion ADFs of the cervical-upper limb area and trunk area were prognostic factors in ALS patients.
    Full-text · Article · Dec 2015
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    ABSTRACT: We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction–based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients.
    No preview · Article · Dec 2015 · Neurobiology of aging
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    ABSTRACT: A human artificial chromosome (HAC) is maintained as an episome within a cell and avoids random integration into the host genome. It can transfer multiple and/or large transgenes along with their regulatory elements thereby resembling native chromosomes. Using this HAC system, we established mesenchymal stem cells (MSCs) that simultaneously expressed hepatocyte growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor 1, termed HAC-MSCs. This cell line provides an opportunity for stable transplantation and thorough analyses. We then introduced the cells for the treatment of a neurodegenerative disorder, amyotrophic lateral sclerosis. The HAC-MSCs were transplanted via the fourth cerebral ventricle (CV) or intravenous (i.v.) infusion at various ages of recipient mice. Littermate- and sex-matched mice underwent a sham procedure. Compared to the controls, there was an encouraging trend of increased life span via CV transplantation and delayed onset in i.v. infusion 60 days after transplantation. Further, we confirmed a statistically significant increase in life span via CV transplantation at 100 days. This effect was not seen in mice transplanted with MSCs lacking the HAC. We successfully enhanced the trophic potential of the MSCs using the HAC. This strategy could be a promising direction for the treatment of neurodegenerative disorders.
    Full-text · Article · Oct 2015 · Molecular Therapy - Nucleic Acids
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    ABSTRACT: A 30-year old man was admitted with right hip pain and gait disturbances. Neurological findings revealed muscular weakness in the lower limbs, hyporeflexia, dysesthesia in the sacral region, and bowel and bladder disturbances. Cerebrospinal fluid (CSF) examination indicated a white blood cell count of 371/μl (lymphocyte:polymorphonuclear leukocyte = 97:3), protein levels of 463 mg/dl and sugar of 20 mg/dl. Although CSF culture was negative, tuberculous infection was presumed. Magnetic resonance imaging revealed areas of enhancement in the intramedullary region surrounding the spinal cord and cauda equina. Enhanced computed tomography (CT) of the abdomen revealed lymph node swelling around the head of the pancreas. Biopsy of the lymph node swelling was culture-positive for Mycobacterium tuberculosis. Hence, assuming a diagnosis of tuberculous lymphadenitis of the abdomen, antitubercular drugs were started. Since antitubercular therapy had beneficial effects on the neurological symptoms and CSF findings, we diagnosed the patient with tuberculous myeloradiculitis. Systematic examinations including lymph node biopsy and cultures were useful for the diagnosis of tuberculous myeloradiculitis.
    No preview · Article · Sep 2015
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    ABSTRACT: Cu, Zn-superoxide dismutase (SOD1), an enzyme implicated in the progression of familial amyotrophic lateral sclerosis (fALS), forms amyloid fibrils under certain experimental conditions. As part of our efforts to understand ALS pathogenesis, in this study we found that reduction of the intramolecular disulfide bond destabilized the tertiary structure of metal free wild-type SOD1 and greatly enhanced fibril formation in vitro. We also identified fibril core peptides that are resistant to protease digestion by using mass-spectroscopy and Edman degradation analyses. Three regions dispersed throughout the sequence were detected as fibril core sequences of SOD1. Interestingly, by using three synthetic peptides that correspond to these identified regions, we determined that each region was capable of fibril formation, either alone or in a mixture containing multiple peptides. It was also revealed that by reducing the disulfide bond and causing a decrease in the structural stability, the amyloid fibril formation of a familial mutant SOD1 G93A was accelerated even under physiological conditions. These results demonstrate that by destabilizing the structure of SOD1 by removing metal ions and breaking the intramolecular disulfide bridge, multiple fibril-forming core regions are exposed, which then interact with each another and form amyloid fibrils under physiological conditions. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
    No preview · Article · Aug 2015 · Journal of Biochemistry
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    ABSTRACT: Objectives The pathogenesis of Alzheimer's disease (AD) is strongly correlated with the aggregation and deposition of the amyloid beta (Aβ1-42) peptide in fibrillar form, and many studies have shown that plant-derived polyphenols are capable of attenuating AD progression in various disease models. In this study, we set out to correlate the effects of anthocyanoside extracts (Vaccinium myrtillus anthocyanoside (VMA)) obtained from bilberry on the in vitro progression of Aβ fibril formation with the in vivo effects of this compound on AD pathogenesis. Methods Thioflavin T fluorescence assays and atomic force microscopy were used to monitor Aβ amyloid formation in in vitro assays. Effects of Aβ amyloids on cellular viability were assayed using cultured Neuro2a cells. Cognitive effects were probed using mice that simultaneously expressed mutant human Aβ precursor and mutant presenilin-2. Results Addition of VMA inhibited the in vitro formation of Aβ peptide fibrils and also reduced the toxicity of these aggregates toward Neuro2a cells. A diet containing 1% VMA prevented the cognitive degeneration in AD mice. Curiously, this diet-derived retention of cognitive ability was not accompanied by a reduction in aggregate deposition in brains; rather, an increase in insoluble deposits was observed compared with mice raised on a control diet. Discussion The paradoxical increase in insoluble deposits caused by VMA suggests that these polyphenols divert Aβ aggregation to an alternate, non-toxic form. This finding underscores the complex effects that polyphenol compounds may exert on amyloid deposition in vivo.
    No preview · Article · Aug 2015 · Nutritional Neuroscience
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    ABSTRACT: Parkinsonism is often observed in the elderly. To clarify the prevalence of parkinsonism-associated diseases and conditions, we conducted a population-based study in a rural island town in western Japan, Ama-cho. Participants included 924 subjects aged 65 years or older residing in the town. Between 2008 and 2011, participants were assessed via standardized neurological examination scales, and Brain MRIs were carried out in 2010. Based on the results of assessment using the modified Unified Parkinson's Disease Rating Scale and a standardized neurological examination, participants were diagnosed as having parkinsonism or mild parkinsonian signs (MPS), or as displaying normal motor conditions (M-normal). Of the 729 participants screened, 70 subjects were diagnosed as having parkinsonism, corresponding to a crude prevalence rate of 9.6% (95% CI, 7.9-11.3%), while 167 MPS subjects (22.9%) and 492 subjects experiencing M-normal (67.5%) were observed. Parkinsonism was found in association with various diseases such as Vascular parkinsonism, Lewy body disease, Alzheimer's disease (AD), and idiopathic normal-pressure hydrocephalus. Among the subjects with dementia, the proportion with parkinsonism was higher in the non-AD dementia group. Parkinsonism occurs in association with several diseases in elderly people. Parkinsonism was also found to be commonly associated with cognitive impairment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Aug 2015 · Acta Neurologica Scandinavica
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    ABSTRACT: High plasma levels of brain natriuretic peptide (BNP) may also be observed in patients with non-cardioembolic infarction (CEI). We aimed to evaluate the relation between plasma BNP level, clinical parameters, and functional outcome in patients with and without CEI. This study analyzed consecutive Japanese patients with acute ischemic stroke. Correlations between plasma BNP level and conventional risk factors for ischemic stroke were examined. Values of P less than .05 were considered statistically significant. This study analyzed 718 acute ischemic stroke patients (445 men and 273 women; mean age, 73.9 years). Mean plasma level of BNP was significantly higher for CEI (366.6 pg/ml) than for non-CEI (105.6 pg/ml; P < .01). Poor outcome (modified Rankin Scale score ≥3) at hospitalization and discharge were associated with significantly higher plasma BNP level than good outcome (modified Rankin Scale score ≤2) for both CEI and non-CEI. On multiple regression analysis, log-BNP was significantly associated with female sex, smoking, triglyceride, and creatinine clearance in CEI. In non-CEI, log-BNP was significantly associated with systolic/diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and creatinine clearance. Irrespective of the presence of CEI, plasma BNP offers a marker of prognostic functional outcome. We clarified the characteristics and differences associated with plasma BNP in CEI and non-CEI, and our results suggest that plasma BNP can provide a useful marker of brain damage and neurohumoral dynamics in acute ischemic stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jul 2015 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
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    ABSTRACT: Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant cerebellar ataxia commonly observed in Japan. However, few neuropathological examinations have been conducted. Here we report the case of a 76-year-old Japanese male SCA31 patient. He noticed dysarthria and difficulty walking at 65 years old. His symptoms subsequently deteriorated, although he could still walk with assistance at 70 years. At 73 years, when he could no longer walk, he was admitted to our hospital. He showed severe limb and truncal ataxia. His father and older brother had shown the same symptoms. Brain magnetic resonance imaging showed cerebellar atrophy of the anterior lobe and white matter hyperintensities. He was diagnosed with SCA31 by genetic analysis. Gradually, his cognitive functions and ability to communicate declined. He died of respiratory failure at the age of 76. Neuropathological examination revealed severe Purkinje cell loss that was accentuated in the anterior lobe of the cerebellum. Furthermore, the remaining Purkinje cells showed abnormal processes (that is, halo-like amorphous materials), as has been reported previously. Severe deposition of hyperphosphorylated tau-positive neurites, many senile plaques and amyloid angiopathy were observed in the neocortex. Our findings suggest that in SCA31, accelerated tau and amyloid pathology in the neocortex might induce dementia at the terminal stage.
    No preview · Article · Jun 2015 · Neuropathology
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    ABSTRACT: Lemierre syndrome is a clinical syndrome that presents with internal jugular thrombophlebitis, septicemia and systemic abscess formations. In general, the condition is preceded by oropharyngeal infections. We report a case of a 73-year-old man with Lemierre syndrome, clivus osteomyelitis and a steroid-responsive mass in the cavernous sinus-suprasellar region. He complained of fever, occipital pain, diplopia and right ptosis. Administration of oral steroids ameliorated the ophthalmic symptoms for a period before he was admitted to our hospital. After admission, the severity of his headache advanced, and his ophthalmic symptoms progressed bilaterally. Brain magnetic resonance imaging showed contrast enhancement of the clivus and revealed a mass lesion contrast-enhancement effect in the cavernous sinus-suprasellar region. Fusobacterium nucleatum was detected by blood culture, and computed tomography revealed multiple bacterial emboli in both lung fields and thrombosis of the left internal jugular vein; thus, he was diagnosed with Lemierre syndrome. After venous administration of antibiotics, his fever and headache markedly improved, but the ophthalmic symptoms did not. We prescribed an oral steroid because the cavernous sinus-suprasellar lesion was probably an inflammatory granuloma caused by a para-infectious mechanism rather than by infection. After the series of treatments, his ophthalmic symptoms improved, and the cavernous sinus-suprasellar region mass lesion decreased. He was eventually discharged in a fully ambulatory state and had no ophthalmic difficulties. We thought that the osteomyelitis of clivus was caused by Lemierre syndrome and its inflammatory processes formed the granuloma in the cavernous sinus-suprasellar region. This was a case of Lemierre syndrome with a rare combination of clivus osteomyelitis and a steroid-responsive tumour in the cavernous sinus-suprasellar region that was successfully treated.
    Full-text · Article · Jun 2015
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    ABSTRACT: Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case-control series. We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel-Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14-5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15-5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10(-3)). The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.
    Full-text · Article · Apr 2015
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    ABSTRACT: BACKGROUND AND PURPOSE:Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study. METHODS:We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system. RESULTS:Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio. CONCLUSIONS:Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.
    Full-text · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: We report the case of an 18-year-old Japanese woman with cobalamin (cbl) C disease. She was born between non- consanguineous parents, and had easy fatigability from a childhood. At 14 years old, she developed renal failure, and had repeated psychosis during 2 years. At 16 old, she developed her gait disturbance and her symptoms fluctuated, but the cause of gait disturbance was unclear. At 18 years old, she was admitted with worsening of gait disturbance. Physical examination revealed spastic paraparesis and bilateral peroneal nerve paralyses. Homocystinuria and methylmalonic aciduria were detected, although serum vitamin B12 was within normal range. Gene mutation analysis revealed Gly147Asp (440G>A) and Trp157Ser (470G>C) in the MMACHC gene as a compound heterozygous mutation. We diagnosed her as having late-onset cbl C disease, and her gait disturbance and renal failure improved after intramuscular hydroxocobalamin administration. Although late-onset cbl C disease is rare in Japan, it an important to consider this congenital disease because symptoms are expected to improve by medical intervention.
    Full-text · Article · Feb 2015 · Rinsho shinkeigaku = Clinical neurology
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    ABSTRACT: Background To determine the relationships between regional white matter lesions (WMLs), lifestyle factors, and cognitive, motor function and mood.MethodsA comprehensive evaluation, including brain MRI, blood tests, the Unified Parkinson's Disease Rating Scale, the Mini Mental State Examination, and the Geriatric Depression Scale, was performed for people aged 65 years or older living in Ama-cho on October 1, 2009. Participants were classified by severity of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using the Fazekas score.ResultsOf 900 eligible participants, 688 (76.4%) were enrolled, including 303 men. Significant predictors of severe PVH were older age, lower low-density lipoprotein cholesterol (LDL-C) levels, elevated blood pressure (BP), cerebral infarction, and no current alcohol use. Significant predictors of severe DWMH were older age, lower 1,5-anhydroglucitol (1,5-AG) levels, elevated BP, cerebral infarction, and no current alcohol use. Higher cognitive function was associated with younger age, female sex, mild DWMH, more years of education, and higher high-density lipoprotein cholesterol levels. Depressive symptoms were associated with lower 1,5-AG levels, lower LDL-C levels, moderate to severe PVH, and no current alcohol use.Conclusions White matter lesions in elderly people were related to hypertension and impaired glucose tolerance. The severity of WMLs was associated with cognitive function and mood.
    Full-text · Article · Feb 2015 · Brain and Behavior

Publication Stats

8k Citations
980.18 Total Impact Points


  • 1983-2016
    • Tottori University
      • • Department of Brain and Neurosciences
      • • Faculty of Medicine
      • • Institute of Neurological Sciences
      • • Division of Urology
      • • School of Medicine
      TTJ, Tottori, Japan
  • 2010
    • Hokkaido University
      • Department of Neurology
      Sapporo, Hokkaido, Japan
  • 2001
    • Ogaki Municipal Hospital
      Gihu, Gifu, Japan
    • Mie-chuo Medical Center
      Matsusaka, Mie, Japan
  • 1995
    • Osaka University
      Suika, Ōsaka, Japan