Hospital of National Center for Geriatrics and Gerontology

Ōbu, Japan

Hospital of National Center for Geriatrics and Gerontology

Ōbu, Japan
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Yoshita M.,Kanazawa University | Yoshita M.,Hokuriku National Hospital | Arai H.,Juntendo University | Arai H.,Tohoku University | And 29 more authors.
PLoS ONE | Year: 2015

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. © 2015 Yoshita et al.


Shimada H.,National Center for Geriatrics and Gerontology | Kato T.,Laboratory of Imaging Diagnosis and Technology | Ito K.,Laboratory of Imaging Diagnosis and Technology | Makizako H.,National Center for Geriatrics and Gerontology | And 5 more authors.
European Neurology | Year: 2012

Aim: The current study sought to determine which types of cognitive function are related to atrophy of the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC) in elderly adults. Methods: The subjects were 96 elderly adults (mean age 75.3 years) with mild cognitive impairment. Subjects underwent Wechsler Memory Scale-Revised, logical memory I and II (WMS-R, LM I and II), Rey complex figure retention tests after 3 and 30 min (RCF-3 min and RCF-30 min), digit span backword (DSB), digit symbol-coding (DSC), Stroop Color and Word Test-Interference List (SCWT-IL) as well as magnetic resonance imaging (MRI) and were divided into elderly adults without or with mild to moderate MTA-ERC atrophy, and those with severe atrophy. Results: In all subjects, MTA-ERC atrophy showed significant relationships with age (r = 0.43), education (r = -0.25), WMS-R, LM I (r = -0.21), DSC (r = -0.32), and SCWT-IL (r = 0.32). The mild to moderate atrophy group showed significant relationships between MTA-ERC atrophy and age (r = 0.34), DSC (r = -0.28), and SCWT-IL (r = 0.25). In contrast, in the severe atrophy group, MTA-ERC atrophy was correlated significantly with RCF-3 min (r = -0.70) and RCF-30 min (r = -0.74). The linear regression model included demographic variables and cognitive tests; two variables to survive the step-wise analysis were age (β = 0.374) and SCWT-IL (β = 0.247) in all subjects. Age (β = 0.301), and RCF-30 min (β = -0.521) and age (β = 0.460) remained as a significant variable in the mild to moderate atrophy and severe atrophy groups, respectively. Conclusion: Executive function tests such as SCWT-IL may be useful as a screening tool to identify mild to moderate MTA-ERC atrophy and a decline in the RCF test may suggest severe MTA-ERC atrophy in elderly adults with MCI. Copyright © 2012 S. Karger AG, Basel.


Doi T.,Section for Health Promotion | Doi T.,Kobe University | Shimada H.,Section for Health Promotion | Makizako H.,Section for Health Promotion | And 5 more authors.
Geriatrics and Gerontology International | Year: 2013

Aim: The detection of the early stages in amnesic mild cognitive impairment (aMCI) is considered important in diagnosing progression to Alzheimer's disease. The current study sought to investigate differences in cognitive function between control subjects with no memory loss (control), and subjects in the early stage of aMCI (EMCI) and late stage of aMCI (LMCI). Methods: A total of 100 community-dwelling older adults aged 65years and over were recruited from 1543 potential subjects. Subjects were classified into three groups based on the degree of objective memory impairment; control (n=29), EMCI (n=34) and LMCI (n=37). Multiple neuropsychological tests were carried out to examine cognitive function. Results: The EMCI individuals showed lower cognitive function relative to controls; not only in logical memory, but also in letter fluency (P<0.05). There were no significant differences in neuropsychological scores between the EMCI and LMCI groups, except for category fluency and logical memory. In addition, the EMCI subjects' logical memory score showed a significant relationship with letter fluency, category fluency and digit span backward test performance (P<0.05). Conclusions: These results suggest that the application of multiple neuropsychological tests might be useful in diagnosing older adults with EMCI and LMCI. © 2012 Japan Geriatrics Society.


Yoshida D.,National Center for Geriatrics and Gerontology | Yoshida D.,Japan Foundation for Aging and Health | Shimada H.,National Center for Geriatrics and Gerontology | Makizako H.,National Center for Geriatrics and Gerontology | And 6 more authors.
Aging Clinical and Experimental Research | Year: 2012

Background and aims: Many studies have suggested that social network, leisure activity, and physical activity can have protective effects against dementia and Alzheimer's disease. However, previous studies have not examined the relationship between daily activities and brain atrophy in older adults. This study aimed to explore what kind of daily activities were associated with atrophy of the medial temporal area including the entorhinal cortex (MTA-ERC) in older adults. Methods: In total, 122 older adults (aged 65 and over) with subjective memory complaints or a Clinical Dementia Rating of 0.5 underwent magnetic resonance imaging, and MTA-ERC atrophy was assessed by the voxel- based morphometry method. Based on magnetic resonance imaging data, the subjects were divided into atrophy and non-atrophy groups. Daily activities were assessed using a 20-item questionnaire (e.g., instrumental activities of daily living, social activities), and we compared activity participation between the groups. Results: The atrophy group (n=37) showed significantly lower participation in 4 out of 20 activity items (cleaning, intellectual activity, culture lessons, and using a personal computer) than the non-atrophy group (n=85). Summed scores of these 4 items (range from 0 to 4) were significantly associated with MTA-ERC atrophy even after adjustment for age, sex, education status, and Mini-Mental State Examination score. Conclusions: In conclusion, MTAERC atrophy was associated with cognitive activities or household-related activities requiring planning. © 2012, Editrice Kurtis.


Shimada H.,Center for Gerontology and Social Science | Makizako H.,Center for Gerontology and Social Science | Doi T.,Center for Gerontology and Social Science | Yoshida D.,Center for Gerontology and Social Science | And 5 more authors.
PLoS ONE | Year: 2013

Background: To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Methodology/Principal Findings: Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1:1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05). Conclusions/Significance: The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI. Trial Registration: UMIN-CTR UMIN000003662. © 2013 Suzuki et al.


PubMed | Juntendo University, Toranomon Hospital, The Mutual, Medical Co. LTA and 13 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimers 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.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.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.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.


PubMed | Hospital of National Center for Geriatrics and Gerontology
Type: Journal Article | Journal: Geriatrics & gerontology international | Year: 2013

The detection of the early stages in amnesic mild cognitive impairment (aMCI) is considered important in diagnosing progression to Alzheimers disease. The current study sought to investigate differences in cognitive function between control subjects with no memory loss (control), and subjects in the early stage of aMCI (EMCI) and late stage of aMCI (LMCI).A total of 100 community-dwelling older adults aged 65 years and over were recruited from 1543 potential subjects. Subjects were classified into three groups based on the degree of objective memory impairment; control (n=29), EMCI (n=34) and LMCI (n=37). Multiple neuropsychological tests were carried out to examine cognitive function.The EMCI individuals showed lower cognitive function relative to controls; not only in logical memory, but also in letter fluency (P<0.05). There were no significant differences in neuropsychological scores between the EMCI and LMCI groups, except for category fluency and logical memory. In addition, the EMCI subjects logical memory score showed a significant relationship with letter fluency, category fluency and digit span backward test performance (P<0.05).These results suggest that the application of multiple neuropsychological tests might be useful in diagnosing older adults with EMCI and LMCI.

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