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Objective: To develop a combined index using cognitive function and instrumental activities of daily living (IADL) to discriminate between Clinical Dementia Rating (CDR) scores of 0.5 and 1 in the clinical setting, and to investigate its optimal cutoff values and internal and external validities., Methods: We included outpatients aged 65-89 years with CDR scores of 0.5 or 1. The optimal cutoff values and internal validity were verified using Japanese memory clinic-based datasets between September 2010 and October 2021 [National Center for Geriatrics and Gerontology (NCGG) datasets]. Cognitive function and IADL were assessed using the Mini-Mental State Examination (MMSE) and Lawton Index (LI), respectively. The optimal cutoff values were defined using the Youden Index. To verify internal validity, sensitivity and specificity were calculated using stratified 5-fold cross-validation. To verify external validity, sensitivity and specificity of the optimal cutoff values were assessed in the Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment (ORANGE) Registry dataset between July 2015 and March 2022, which has multicenter clinical data., Results: A total of 800 (mean age, 77.53 years; men, 50.1%) and 1494 (mean age, 77.97 years; men, 43.3%) participants comprised the NCGG and ORANGE Registry datasets, respectively. The optimum cutoff values for men and women were determined as MMSE < 25 and LI < 5 and MMSE < 25 and LI < 8, respectively; such a combined index showed good discriminative performance in internal (sensitivity/specificity: men, 92.50/73.52; women, 88.57/65.65) and external validities (men, 81.43/77.62; women, 77.64/74.67)., Conclusion: The index developed is useful in discriminating between CDR scores of 0.5 and 1 and should be applicable to various settings, such as memory clinics and clinical research., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Aim: Muscle mass and strength correlate with cognitive function; however, it remains unclear whether dynapenia (i.e., muscle weakness with preserved muscle mass) is relevant. This study aimed to explore whether dynapenia is associated with global cognitive function in community-dwelling older Japanese adults., Methods: This cross-sectional study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study, which pooled data from five community-based geriatric cohorts. Dynapenia was defined as muscle weakness without muscle mass loss according to the Asian Working Group for Sarcopenia criteria. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). An ordered logistic regression analysis was conducted with dynapenia as the exposure and with cognitive decline stages, defined as an MMSE score of 27-30 for normal cognition, 24-26 for possible cognitive decline, and <24 for cognitive decline, as the outcome, stratified by sex and adjusted for age, muscle mass, education, alcohol consumption, smoking habits, living alone, and non-communicable diseases., Results: We analyzed data for 3338 participants (2162 female) with preserved muscle mass. Of these, 449 (13.5%) had dynapenia, and 79 (2.4%) exhibited cognitive decline. Multivariate odds ratios (95% confidence interval) for cognitive decline among those with dynapenia, compared with those without dynapenia, were 1.51 (1.02-2.24) for males and 2.08 (1.51-2.86) for females., Conclusions: Muscle weakness is associated with cognitive decline, even in individuals with preserved muscle mass. Further studies are needed to better understand the association between muscle weakness and cognitive decline over time in order to develop dementia prevention strategies for those with dynapenia. Geriatr Gerontol Int 2024; 24: 123-129., (© 2023 Japan Geriatrics Society.)

Aim: Community settings often need simple screening, rather than detailed tests, to identify cognitive impairment. This study aimed to develop models to screen older adults with cognitive impairment., Methods: This study used data from the Integrated Research Initiative for Living Well with Dementia Cohort Study and included 5830 older adults. Individuals were considered cognitively impaired if their Mini-Mental State Examination score was less than 24. Three screening models were developed: the simple model (age, sex, and education), the base model comprising 13 candidate variables available in the questionnaire, and the enhanced model, where grip strength and gait speed were added to the base model. We performed binary logistic regression analysis with stepwise backward elimination (P < 0.1 for retention in the model) to develop each model. Then, we calculated integer scores from coefficients to develop score-based models. The area under the receiver operating characteristic curve (AUC) was used to evaluate discrimination., Results: Participants with cognitive impairment accounted for 4.0% (n = 233) of the total. The score-based simple model comprised three variables (AUC = 0.72, sensitivity: 72%, specificity: 61%). The score-based base model included nine variables (AUC = 0.76, sensitivity: 70%, specificity: 67%). The score-based enhanced model comprised eight variables, including grip strength and gait speed (AUC = 0.79, sensitivity: 73%, specificity: 70%)., Conclusions: This study developed three screening models with acceptable discriminant validity for cognitive impairment. These models comprised simple questionnaire-based items and common physical performance measurements. These models could enable screening of older adults suspected of cognitive impairment without the need to conduct cognitive tests in community settings. Geriatr Gerontol Int 2022; 22: 292-297., (© 2022 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objective: Previous studies have shown associations between the gut microbiota, microbial metabolites, and cognitive decline. However, the effect of the dietary composition on such associations has not been fully investigated. The aims of this study were to evaluate the relationships between adherence to a Japanese-style diet, the gut microbiota, and cognitive decline. Furthermore, we aimed to evaluate the three forms of the Japanese diet index (JDI; the conventional [JDI 9 ], updated [JDI 12 ], and a newly modified JDI) to determine which would show the closest relationships with cognition and the gut microbiota., Methods: We performed a cross-sectional subanalysis of data from a prospective hospital-based cohort study. We assessed the patients' demographic characteristics, dietary composition, risk factors, cognitive function, brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional JDI (JDI 9 ), a 12-component modern JDI (JDI 12 ), and a 12-component revised JDI (rJDI 12 ), were defined. We evaluated the relationships between the JDI scores, cognitive function, and the gut microbiome and microbial metabolites using multivariable logistic regression analyses., Results: We analyzed data from 85 eligible participants (61% women; mean age: 74.6 ± 7.4 y). Compared with participants who had dementia, those without dementia were more likely to consume foods in the JDI 12 , including fish and shellfish (64.5 versus 39.1%, P = 0.048), mushrooms (61.3 versus 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9 versus 30.4%, P = 0.013), and coffee (71 versus 43.5%, P = 0.024). There were non-significant trends toward lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI scores than those without dementia (dementia versus non-dementia, median JDI 9 score: 5 versus 7, P = 0.049; JDI 12 : 7 versus 8, P = 0.017; and rJDI 12 : 7 versus 9, P = 0.006, respectively)., Conclusions: Adherence to a traditional Japanese diet was found to be inversely associated with cognitive decline and tended to be associated with lower concentrations of gut microbial metabolites., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and neurofilament light chain (NfL; a disease-nonspecific biomarker of neural damage) remain controversial., Objective: To evaluate the associations between plasma NfL, gut microbiota, and cognitive function., Methods: We performed a cross-sectional sub-analysis of data from our prospective cohort study that was designed to investigate the relationship between gut microbiota and cognitive function. Patients who visited our memory clinic were enrolled and demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites were assessed. We evaluated the relationships between the gut microbiome, microbial metabolites, and plasma NfL. Moreover, the relationships between plasma NfL and cognitive function were assessed using multivariable logistic regression analyses., Results: We analyzed 128 participants (women: 59%, mean age: 74 years). Participants with high (above the median) plasma NfL concentrations tended to be older, women, and hypertensive and have a history of stroke, chronic kidney disease, and dementia. Plasma NfL was also associated with cerebral small vessel disease. However, plasma NfL levels were not significantly correlated with gut microbial metabolites. Multivariable analyses revealed that a higher plasma NfL concentration was independently associated with the presence of dementia (odds ratio: 9.94, 95% confidence interval: 2.75-48.2, p < 0.001)., Conclusion: High plasma NfL concentration was independently associated with the presence of dementia as previously reported. However, plasma NfL levels were not significantly correlated with gut microbial metabolites in this preliminary study.

Background: Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial., Objective: To evaluate associations between plasma LPS, gut microbiota, and cognitive function., Methods: We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses., Results: Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14-3.84, p = 0.007)., Conclusion: In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline.

Aim: The aim of this study was to examine the ability of a group-based multi-component psycho-educational intervention (GMC-PEI) to reduce depression, and improve caregiving appraisals, coping skills of informal caregivers and the condition of people with dementia., Methods: In this randomized controlled and blinded trial, we enrolled 54 informal caregivers of people with dementia visiting the Japan National Center of Geriatrics and Gerontology, and divided them into GMC-PEI and control groups. The intervention group received a 12-week GMC-PEI program that included six 2-h structured sessions to enhance their knowledge of dementia, caregiving skills and coping skills. The control group received leaflets containing information about dementia. We evaluated caregivers' depression, caregiving time, subjective burden, caregiving appraisal and care coping skills. We also evaluated people with dementia at baseline and 12 weeks, and reassessed 20 participants from the intervention group at 24 and 48 weeks., Results: The GMC-PEI significantly improved depression, positive appraisals of fulfillment in caregiving, affection for care recipients, self-growth and coping skills, such as seeking formal support. Depression, fulfillment and affection for people with dementia showed a peak improvement at 24 weeks; formal support-seeking showed a linear improvement throughout the 48-week follow-up period., Conclusions: The group-based multi-component psycho-educational intervention reduced depression, improved self-appraisal and enhanced coping skills in caregivers. However, emotional enhancements dissipated sooner than support-seeking skills, suggesting that caregivers should be reviewed every 12-24 weeks. Geriatr Gerontol Int 2021; 21: 561-567., (© 2021 Japan Geriatrics Society.)

Dysregulation of the gut microbiome is associated with dementia. However, the relationship between microbiome-associated metabolites and dementia has yet to be identified. Outpatients visiting a memory clinic in Japan enrolled in this cross-sectional study; 107 subjects were eligible for the study, 25 of which had dementia. We collected demographics, activities of daily living, risk factors, cognitive function, and brain imaging data. The gut microbiome was assessed using terminal restriction fragment length polymorphism analysis. Concentrations of faecal metabolite were measured. We used multivariable logistic regression analyses to identify whether metabolites were independently related to dementia. The concentrations of metabolites were significantly different between subjects with and those without dementia. Every 1 standard deviation increment in faecal ammonia concentration was associated with around a 1.6-fold risk for the presence of dementia. A higher faecal lactic acid concentration was related to a lower risk of dementia, by around 60%. A combination of higher faecal ammonia and lactic acid concentrations was indicative of the presence of dementia, and had a similar predictive value as traditional biomarkers of dementia. Thus, faecal ammonia and lactic acid are related to dementia, independently of the other risk factors for dementia and dysregulation of the gut microbiome.

Background: Very few studies have investigated the impact of cognitive frailty in clinical settings, especially in memory clinic populations., Objective: To examine the impact of cognitive frailty on activities of daily living (ADL), cognitive function, and conversion to dementia among memory clinic patients with mild cognitive impairment (MCI)., Methods: The subjects of this retrospective study were 248 MCI patients (mean age, 76.3±5.4 years; females, 60.9%). All subjects completed a comprehensive geriatric assessment at baseline and at least one assessment during 3-year follow-up. Frailty was defined by generating a frailty index (FI), and MCI patients with frailty (FI≥0.25) were considered to represent cognitive frailty. As primary outcomes, the Barthel Index, Mini-Mental State Examination, and incident dementia were evaluated during follow-up. At baseline, patients were assessed for apolipoprotein E (APOE) phenotype. A linear mixed model, as well as a Cox proportional hazards regression model with adjustment for confounding variables, was performed., Results: Of these patients, 75 (30.2%) were classified as cognitive frail. APOEɛ4 carriers accounted for 26.7% of those with cognitive frailty and 44.5% of those without (p = 0.008). Cognitive frail patients showed a faster ADL decline (estimate, -1.04; standard error, 0.38; p = 0.007) than patients without cognitive frailty. Cognitive frailty was not associated with cognitive decline and incident dementia., Conclusion: Our findings demonstrated cognitive frailty increases the risk of dependence but not cognitive outcomes. Cognitive frailty may have heterogeneous conditions, including APOEɛ4-related pathologies, which may affect the cognitive trajectories of patients with MCI.

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.

We examined the nutritional status and its association with behavioral psychiatric symptoms of dementia (BPSD) among 741 memory clinic patients (normal cognition (NC), 152; mild cognitive impairment (MCI), 271; early-stage Alzheimer disease (AD), 318). Nutritional status and BPSD were assessed using the Mini Nutritional Assessment Short-Form (MNA-SF) and the Dementia Behavior Disturbance Scale (DBD), respectively. Compared to subjects with NC, more subjects with MCI and early-stage AD were at risk of malnutrition (MNA-SF, 8-11: NC, 34.2%; MCI, 47.5%; early-stage AD, 53.8%) and were malnourished (MNA-SF, 0-7: NC, 4.6%; MCI, 5.9%; early-stage AD, 8.2%). Among patients with MCI or early-stage AD, those at risk of/with malnutrition showed higher DBD scores than those well-nourished (12.7 ± 9.0 vs. 9.5 ± 7.3; p < 0.001). Moreover, analysis of covariance adjusting for confounders showed that nutritional status was significantly associated with specific BPSD, including "verbal aggressiveness/emotional disinhibition" (F = 5.87, p = 0.016) and "apathy/memory impairment" (F = 15.38, p < 0.001), which were revealed by factor analysis of DBD. Our results suggest that malnutrition is common among older adults with mild cognitive decline, and possibility that nutritional problems are associated with individual BPSD.

Dysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of 'other' bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.

Introduction: Non-valvular atrial fibrillation (NVAF) is known as a robust risk factor for stroke. Recent reports have suggested a risk of dementia with NVAF, but much remains unknown regarding the relationship between this mechanism and the potential protective effects of novel anticoagulants (direct oral anticoagulants (DOACs), or non-vitamin K oral anticoagulants)., Methods and Analysis: This study, the strategy to obtain warfarin or DOAC's benefit by evaluating registry, is an investigator-initiated, multicentre, prospective, observational, longitudinal cohort study comparing the effects of warfarin therapy and DOACs on cerebrovascular diseases and cognitive impairment over an estimated duration of 36 months. Once a year for 3 years, the activities of daily living and cognitive functioning of non-demented patients with NVAF will be assessed. Demographics, risk factors, laboratory investigations, lifestyle, social background and brain MRI will be assessed., Ethics and Dissemination: This protocol has been approved by the ethics committee of the National Center for Geriatrics and Gerontology (No. 1017) and complies with the Declaration of Helsinki. Informed consent will be obtained before study enrolment and only coded data will be stored in a secured database. The results will be published in peer-reviewed journals and presented at scientific meetings to ensure the applicability of the findings in clinical practice., Trial Registration Number: UMIN000025721., Competing Interests: Competing interests: NS reports grants from Research Funding of Longevity Sciences from the National Center for Geriatrics and Gerontology, grants from Japan Foundation for Aging and Health, grants from the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program, grants from Funds for Research and Development Grants for Longevity Science from the Japan Agency for Medical Research and Development., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The goal of dementia treatment is to improve the quality of life for both people with dementia and their families. Rehabilitation as a non-pharmacological approach, coordinated with pharmacological treatment, aims to allow patients to live better by slowing the progression, and relieving the behavioral and psychological symptoms of dementia. In dementia, the manifestation of symptoms caused by neurological impairment is modified by various factors; thus, multidimensional assessment and approaches are effective based on the concept of the International Classification of Functioning, which emphasizes the healthy components of every person's functioning. Regarding the process of rehabilitation, every person with dementia should take initiative throughout the course of rehabilitation, and shared decision-making is a fundamental requirement at every phase of intervention. The needs of rehabilitation differ depending on the stage of dementia. In the early stages, cognitive rehabilitation is needed, and interventions are carried out using preserved functions and compensatory strategies. As the disease progresses, capacities of instrumental and then basic activities of daily living deteriorate, and interventions need to be tailor-made and carried out in the context of actual living situations. In the early-to-moderate stages, prevention and management of behavioral and psychological symptoms of dementia are required. In the interventions to alleviate behavioral and psychological symptoms of dementia, it is critical to consider the individual and the meaning behind his/her behaviors from a holistic perspective. Family carers also need support, and education to learn coping strategies can be beneficial for both people with dementia and their carers. Rehabilitation can empower people with dementia and their families to live better with dementia. Geriatr Gerontol Int 2018; 18: 1529-1536., (© 2018 Japan Geriatrics Society.)

Aim: The present study aimed to: (i) examine the reliability and validity of the Dementia Assessment Sheet for Community-based Integrated Care System 21-items for classifying patients to the appropriate categories for glycemic targets in older patients; and (ii) develop a short version of the tool and examine its reliability and validity., Methods: A total of 410 older individuals were recruited for this multicenter cross-sectional study. We classified them into three categories used for determining the glycemic target in older patients in Japan based on cognitive functions and activities of daily living. Exploratory factor analyses were used to select the eight items of the shorter version. The reliability and validity of the assessment tools were assessed using Cronbach's alpha coefficients and receiver operating characteristic analyses, respectively., Results: The Dementia Assessment Sheet for Community-based Integrated Care System 21-items had three latent factors: cognitive function, instrumental activities of daily living and basic activities of daily living. The Dementia Assessment Sheet for Community-based Integrated Care System 8-items was developed based on each factor load quantity and was confirmed to have a strong correlation with the original version (r = 0.965, P < 0.001). Both tools significantly discriminated older adults belonging to category I from those belonging to category II or III, and category III from category I or II., Conclusions: Both tools had sufficient internal consistency and validity to classify older patients into the categories for determining the glycemic target in this population based on cognitive and daily functions. Geriatr Gerontol Int 2018; 18: 1458-1462., (© 2018 Japan Geriatrics Society.)

Aim: Physical and cognitive functions are mutually associated. However, it is unknown which markers of physical functions or body composition are most strongly associated with cognition. Here, we explored the association between body composition/physical performance and comprehensive neuropsychological assessments in an effort to identify reliable markers of cognition among factors in body composition/physical performance, including both usual and maximum gait speeds., Methods: We examined a total of 161 Japanese individuals (71 men, 90 women; aged 76.3 ± 7.2 years) with a Clinical Dementia Rating of 0.5 and a Mini-Mental State Examination score >24. A battery of neuropsychological assessments, physical functional assessments and measurements of body composition was carried out. We conducted a multiple regression analysis to investigate the associations between cognitive performance and the factors in body composition and physical performance with adjustments for age, sex, and number of school years., Results: Maximum gait speed was the factor most widely associated with cognitive performance among the factors of body composition and physical performance., Conclusion: Maximum gait speed might be the best marker for cognition in this population of older individuals. Geriatr Gerontol Int 2018; 18: 1323-1329., (© 2018 Japan Geriatrics Society.)

Aim: Behavioral and psychological symptoms of dementia are an important source of distress for caregivers. The aim of the present study was to evaluate the effectiveness of educational intervention using printed educational material for reducing distress induced by behavioral and psychological symptoms of dementia among caregivers working at facilities without medical specialists and/or registered nurses., Methods: A cluster quasi-randomized, controlled comparative trial was carried out at 17 facilities in Japan. Our intervention was an educational program administered at baseline using printed educational material for the care staff. The primary outcome was evaluated using the Japanese version of the Neuropsychiatric Inventory Questionnaire. The secondary outcome measures were caregiver burnout evaluated using the Japanese version of the Maslach Burnout Inventory and the care dependency of residents measured using the Japanese version of the Care Dependency Scale., Results: The total Neuropsychiatric Inventory Questionnaire score decreased significantly in the intervention group (F [1355] = 6.57, P = 0.01), and the difference between the intervention and control groups was also significant (F [1355] = 4.78, P = 0.03). There were no significant changes in the Maslach Burnout Inventory or Care Dependency Scale scores in the intervention group, while the Maslach Burnout Inventory subscale (personal accomplishment) score decreased significantly in the control group., Conclusions: Our intervention achieved a significant reduction of distress among caregivers working at care homes without medical specialists and/or registered nurses. The findings of this research show that educational intervention can make a valuable contribution to training programs for care staff. Geriatr Gerontol Int 2018; 18: 487-494., (© 2017 Japan Geriatrics Society.)

The Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment in Japan (ORANGE platform) is a recently established nationwide clinical registry for dementia. This platform consists of multiple registries of patients with dementia stratified by the following clinical stages: preclinical, mild cognitive impairment, early-stage, and advanced-stage dementia. Patients will be examined in a super-longitudinal fashion, and their lifestyle, social background, genetic risk factors, and required care process will be assessed. This project is also notable because the care registry includes information on the successful, comprehensive management of patients with dementia. Therefore, this multicenter prospective cohort study will contribute participants to all clinical trials for Alzheimer's disease as well as improve the understanding of individuals with dementia.

With the aging of society, the number of elderly with reduced cognitive function has been increasing worldwide. As a test to measure the cognitive function, the Revised Hasegawa's Dementia Scale (HDS-R) has been used in Japan, Korea, and China. Since there was no HDS-R version for Laotians, the questionnaire and manual were developed through the cooperation of Lao and Japanese researchers. Back-translation was conducted to confirm the accuracy of the translation. The score on the 9-item HDS-R ranges 0 to 30 points, and reduced cognitive function is usually defined as a score of 20 points or lower. After receiving explanation regarding the use of the tool and practicing its implementation, 3 female doctors interviewed 30 superficially healthy volunteers aged 31 to 84 years (12 males and 18 females) who lived with his/her family in Vientiane Capital, Lao PDR. Their score distributed from 4 to 30 points, with an average of 24.7 (standard deviation 5.4) points. Six (20.0%) participants scored 20 points or lower. The discussion before and after the pilot interviews revealed that the following changes needed to be made in accordance to the culture of Lao people; 1) order of date in Question 2, 2) words to be memorized in Questions 4 and 7, 3) objects to be memorized using pictures, not actual objects, in Question 8. Additionally, we introduced new two rules; a clear time definition for no reply (10 seconds), and repetition of questions twice for those with ear problems. The revised version of the HDS-R was thought to be an appropriate standard questionnaire for use in studies on cognitive function among Laotians.

Frailty is a predictor of functional decline, falls, hospitalization, and mortality. Fried et al. developed the frailty index, which include 5 simple items: weight loss, weakness, exhaustion, slowness, and low activity. Likewise, sarcopenia indicates an age-related decline in skeletal muscle mass as well as muscle function, which may result in reduced physical capability, poorer quality of life, impaired cardiopulmonary performance, unfavorable metabolic effects, falls, disability, and mortality. Both frailty and sarcopenia could be associated with mild cognitive impairment which leads to dementia. Thus, early initiation of a comprehensive geriatric health examination and a multidomain intervention such as diet, exercise, cognitive training, and vascular risk monitoring may be useful to prevent frailty and sarcopenia in community-dwelling older adults.

Background: The current state of eye diseases and treatments in the elderly as well as the relationships between dementia and systemic diseases remain unclear. Therefore, this study evaluated the prevalence of eye diseases, visual impairment, cognitive impairment, and falls (which are an important health issue and are considered one of the Geriatric Giants) in super-elderly people in Japan., Methods: The subjects were 31 elderly people (62 eyes; mean age: 84.6 ± 8.8 years; age range 61-98 years) who were admitted to a geriatric health services facility. Eye treatment status, systemic diseases, dementia, and recent falls were investigated. Eye examinations including vision and intraocular pressure measurement, and slit-lamp biomicroscopy were conducted., Results: Mean best corrected visual acuity (logMAR) was 0.51 ± 0.56, and mean intraocular pressure was 13.7 ± 3.5 mmHg. Approximately half of the subjects exhibited excavation of the optic nerve head including cataracts and glaucoma. Ten subjects had visual impairment (i.e., visual acuity of the eye with the better vision <20/40). The mean Hasegawa dementia scale scores between the visually impaired and non-visually impaired groups were 10.2 ± 6 and 16 ± 8 points, respectively (p < 0.05). Furthermore, 70% of subjects with visual impairment experienced a fall in the past year compared to 48% of those without visual impairment, although the difference was not significant. Regarding systemic diseases, there were 6, 5, and 15 cases of diabetes, hyperlipidemia, and hypertension, respectively. There was no significant difference between these systemic diseases and visual function after adjusted for age and gender., Conclusions: The percentages of patients with age-related eye diseases and poor visual acuity in a geriatric health services facility were extremely high. Compared to those without visual impairment, those with visual impairment had lower dementia scores and a higher rate of falls.

Now that the number of elderly people has increased and the number of dementia patients is rapidly increasing, dementia might be regarded as a common disease. Under these circumstances, the establishment of systems to support the elderly with dementia from the early stages, and to provide primary care doctors and care workers with necessary education is an urgent issue. Up to the end of 2012, a total of 2680 doctors had been certified as Dementia Support Doctors (DSD). The DSD's function and roles are: (i) to support primary care doctors and care specialists involved in the medical care, and general care of dementia patients; (ii) to facilitate multidisciplinary cooperation led by a Community General Support Center; and (iii) to give lectures about dementia to primary care doctors and educate people in the community. DSD are more skilled than primary care doctors in the following functions: differential diagnosis; outpatient services to deal with behavioral and psychological symptoms of dementia; community liaison; and home care., (© 2014 Japan Geriatrics Society.)

Aim: The National Center for Geriatrics and Gerontology has begun to provide educational support for family caregivers through interdisciplinary programs focusing on patients in the early stage of dementia. These interdisciplinary programs have established two domains for the purpose of "educational support": cure domains (medical care, medication) and care domains (nursing care, welfare). In the present study, we examined the learning needs and post-learning attitude changes of patients and their families who participated in these programs in order to assess the effectiveness of an interdisciplinary program of educational support in each of these domains., Methods: A total of 170 participants (51 dementia patients, 119 family members) were included in the study. Data were obtained from electronic health records, and through a written survey administered before and immediately after each program., Results: A high percentage of patients and family members desired knowledge about the progression and symptoms of dementia, as well as measures to prevent progression, both of which fall under the medical care content. For patients, education in the medical care content increased their motivation to live. For families, education in the medical and nursing care contents promoted their understanding of dementia, while education in medication and welfare contents improved their skills for handling dementia patients and their symptoms., Conclusion: Both patients and family members expressed a need to learn medical care content, including the progression and disease symptoms of dementia, and methods to prevent the progression of dementia symptoms. Their responses showed that learning medical care was effective for understanding dementia. We suggested that medical care content was the core of interdisciplinary educational support for early-stage dementia patients and their family members., (© 2014 Japan Geriatrics Society.)

Aim: To examine the efficacy of rehabilitation for elderly individuals with dementia at intermediate facilities between hospitals and home, based on the policies for elderly individuals to promote community-based care at home and dehospitalization., Methods: Participants were older adults with dementia newly admitted to intermediate facilities. A total of 158 in the intervention group who claimed Long-Term Care Insurance for three consecutive months, and 54 in the control group were included in the analysis. The interventions were carried out in a tailor-made manner to meet individual needs. The personal sessions were carried out three times a week for 3 months after admission by physical, occupational or speech therapists. Outcome measures were cognitive tests (Hasegawa Dementia Scale revised [HDS-R] and Mini-Mental State Examination), and observational assessments of dementia severity, activities of daily living (ADL), social activities, behavioral and psychological symptoms of dementia (BPSD) using a short version of the Dementia Disturbance Scale (DBD13), depressive mood, and vitality., Results: Significant improvement in the intervention group was shown in cognitive function measured by HDS-R (interaction F[1, 196] = 5.190, P = 0.024), observational evaluation of dementia severity (F[1,198] = 9.550, P = 0.002) and BPSD (DBD13; F[1,197] = 4.506, P = 0.035). Vitality, social activities, depressive mood and ADL were significantly improved only in the intervention group, although interaction was not significant., Conclusions: Significant improvement by intervention was shown in multiple domains including cognitive function and BPSD. Cognitive decline and worsening of BPSD are predictors of care burden and hospitalization, thus intensive rehabilitation for dementia was beneficial for both individuals with dementia and their caregivers., (© 2013 Japan Geriatrics Society.)

Aim: We aimed to determine whether plasma sex hormone levels are associated with activities of daily living (ADL), cognition, depression and vitality in elderly individuals with functional decline., Methods: Two hundred and eight consecutive persons 70 years or older (108 men and 100 women; mean +/- standard deviation, 81 +/- 7 years) with a chronic stable condition, receiving long-term care at a long-term care facilities located in Nagano Prefecture, Japan, were enrolled. Plasma total testosterone, free testosterone (only in men), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S) and estradiol levels were determined in the morning after an overnight fast. Comprehensive geriatric assessment was performed including basic ADL by Barthel Index, instrumental ADL, cognitive function by Hasegawa Dementia Scale--Revised, mood by Geriatric Depression Scale and ADL-related vitality by Vitality Index., Results: Simple regression analysis showed that, in men, plasma total and free testosterone levels were associated with basic ADL (R = 0.292 and R = 0.282), instrumental ADL (R = 0.261 and R = 0.408), cognitive function (R = 0.393 and R = 0.553) and vitality (R = 0.246 and R = 0.396), while DHEA(-S) was associated with cognitive function, and estradiol with cognitive function as well as vitality. In women, the only significant correlation was between DHEA(-S) and basic ADL. Adjustment for age and nutritional markers did not influence the associations of plasma sex hormone levels with functional scores except for that of free testosterone with Barthel Index., Conclusion: These results suggest that sex hormones have sex-specific associations with physical and neuropsychiatric functions in elderly individuals, and that endogenous testosterone is related to global function in elderly men.

The effectiveness and safety of yokukansan (TJ-54), a traditional Japanese medicine (kampo) for the treatment of the behavioural and psychological symptoms of dementia (BPSD), were evaluated in 106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. Patients were randomly assigned to group A (TJ-54 treatment in period I and no treatment in period II; each period lasting 4 wk) or group B (no treatment in period I and TJ-54 treatment in period II). BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. The effects of TJ-54 persisted for 1 month without any psychological withdrawal symptoms in group A. TJ-54 did not show any effect on either cognitive function or ADL. No serious adverse reactions were observed. The present study suggests that TJ-54 is an effective and well-tolerated treatment for patients with BPSD.

Several bedside portable swallowing tests have been advocated for screening for dysphagia. However, the clinical usefulness and limitation of these tests have not been examined in elderly patients with dementia. We performed the repetitive saliva swallowing test (RSST) and the simple swallowing provocation test (SSPT) in 37 elderly inpatients (81.8 +/- 1.2 years old). Simultaneously, cognitive and verbal communication ability were assessed by the Hasegawa Dementia Scale revised version (HDSR) and the Mini-Communication Test (MCT). RSST was completed only in 22 patients (59%), whereas SSPT was successfully completed in all cases. Scores of HDSR and MCT were significantly lower in patients who were unable to cooperate with RSST compared to successful examinees (HDSR: 7 +/- 1 vs 15 +/- 3, p < 0.0; MCT: 47 +/- 8 vs 81 +/- 5, p < 0.01). Dysphagia was detected in 14 patients (64%) by RSST and 5 (14%) by SSPT. Patients with dysphagia showed significantly lower cognitive function (p < 0.05) and verbal communication ability (p < 0.05). In conclusion, RSST is more sensitive to detect dysphagia in elderly patients; however, compliance with RSST is strongly influenced by the patient's cognitive function and verbal communication ability. Comprehensive geriatric assessment will help to choose an alternative test for dysphagia such as SSPT which is more specific test for aspiration pneumonia.

Since the introduction of long-term care insurance, day care services have become popular throughout Japan and many kinds of behavioral approaches have been used. Although there have been many reports on the non-pharmacological effects on cognitive function, case control studies to evaluate the effect of day care services are insufficient Furthermore, no study has compared the advantages of different behavioral therapies for elderly subjects with loss of cognitive function. To clarify these issues, we compared the changes in activities of daily living, cognitive function and vitality/depression among 78 subjects receiving different day care services. Community dwelling subjects using day care (day care group: n = 29, 80+/-7.3 years old) showed an improvement in abnormal behavior (DBD scale; before 8.5+/-2.1, after 3.2+/-1.3, p<0.05). Vitality and volition measured by the Vitality Index were significantly preserved in the day care group compared with community dwelling subjects without day care services (n = 11, 78.6+/-9.4 y.o.). Comparing the effect of three different behavioral therapies (physical fitness, cooking and gardening), there was no difference in changes in cognitive function or in other comprehensive measurements among the groups. On the other hand, different responses to various therapies were observed among subjects. To determine the advantage of various non-pharmacological therapies for dementia, geriatricians need to perform prospective case-control studies with a large number of subjects, using comprehensive geriatric assessment as the art of a geriatrician.

To evaluate verbal communication ability in the elderly, we developed a new portable "mini-communication test (MCT)" with 13 sub-scales, which was constructively validated based on 45 items from other reported scales. Clinical reliability and validity were tested in 354 inpatients in a long-term care hospital (81.9 +/- 8.3 years old) and 124 inpatients (80.39 +/- 8.1 years old) and 34 outpatients (76.5 +/- 7.0 years old) in Kyorin University Hospital. All patients were evaluated in approximately 7 minutes each. The test-retest correlation coefficient was 0.99. Inter-rater coefficient of variation was 0.107. The Cronbach alpha value of the test was 0.93. MCT positively correlated with the Barthel Index (r = 0.65, p < 0.01). Hasegawa Dementia Scale Revised version (r = 0.93, p < 0.001) and Vitality Index (r = 0.66, p < 0.01). MCT could be a new tool to assess communication ability in elderly patients with or without dementia.

BackgroundParticipant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials.ObjectiveTo determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial.MethodsIn this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N.ResultsPlasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p

Background: With increasingly aging societies, a comprehensive strategy for dementia research is important. The Organized Registration for the Assessment of dementia by the Nationwide General consortium toward Effective treatment (ORANGE) Registry is the first longitudinal multicenter prospective trial-ready cohort in Japan.Objective: To establish a large cohort for use in clinical trials and research in Japan.Methods: This registry, based on communities, hospitals, and nursing homes, covers three dementia stages (preclinical, mild cognitive impairment [MCI], and advanced dementia), and includes more than 30 hospitals. We analyzed enrollment and 1-year follow-up data for disease progression.Results: There were 1450 registered patients (649 men, 801 women; mean age, 77.92±6.70 years; mean Mini-Mental State Examination [MMSE] score, 25.19±2.76). The conversion rates from MCI to dementia and MCI to normal were 14.3% and 1.1%, respectively. High Clinical Dementia Rating score (odds ratio [OR] = 11.085, 95% confidence interval [CI]:1.619-75.913, p = 0.014), low MMSE score (OR = 0.835, 95% CI: 0.761-0.917, p < 0.001), high Geriatric Depression Scale score (OR = 1.093, 95% CI: 1.005-1.189, p = 0.038), and low body mass index (OR = 0.895, 95% CI: 0.829-0.967, p = 0.005) at enrollment were significant factors for conversion.Conclusion: The ORANGE MCI Registry is an established registry that facilitates creation of trial-ready cohorts to accelerate promotion of clinical trials with low reversion rates as it originates from a hospital. One-year follow-up analysis suggested assessing various factors for conversion risk. Further analyses will be possible in future with registry expansion. We will continue to refine this registry, including how it can be used more efficiently. [ABSTRACT FROM AUTHOR]

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are exhibited in most patients with Alzheimer disease (AD). Although white matter hyperintensity (WMH) is often observed with AD, the precise role of WMH in BPSD remains unclear. The current study aimed to identify the impact of regional WMH on specific features of BPSD in persons with mild to moderate AD and amnestic mild cognitive impairment (aMCI). Methods: A sample of 256 female outpatients with AD (n = 217) and aMCI (n = 39) were recruited. We assessed BPSD using the Dementia Behavior Disturbance Scale. WMH and brain atrophy were evaluated using an automatic segmentation program. Regional WMH was evaluated as periventricular hyperintensity (PVH) and deep WMH in frontal, temporal, occipital, and parietal lobes. Results: Whole-brain WMH was associated with verbal aggressiveness. In multivariate analysis, PVH in the frontal lobe was independently associated with verbal aggressiveness after adjustment for brain atrophy and clinical confounders. Conclusion: The current results indicated that PVH in the frontal lobe was independently associated with verbal aggressiveness. [ABSTRACT FROM AUTHOR]

Background: Instrumental activities of daily living (IADL) start to decline during the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). Cognitive and physical decline are involved in the loss of functional independence. However, little is known about AD-related neural change that leads to IADL impairment. The purpose of this study was to clarify the effects of regional white matter hyperintensity (WMH) on IADL impairment in persons with AD and aMCI. Methods: The participants were 347 female subjects aged 65–85 years diagnosed with AD (n = 227), aMCI (n = 44) or normal cognition (n = 76). IADL was assessed by the Lawton Index. Cognition, mood and mobility function were evaluated by comprehensive geriatric assessment batteries. WMH and brain atrophy were analyzed with brain magnetic resonance imaging, using an automatic segmentation program. Regional WMH was measured in the frontal, temporal, occipital and parietal lobes. Results: Ability to carry out IADL of shopping, food preparation, mode of transportation, responsibility for own medication, and ability to handle finances was obviously impaired in the early stage of AD. Frontal WMH was specifically associated with disability to do shopping and food preparation even after adjusting for several confounders including brain atrophy. Conclusions: IADL subcategories were differentially impaired along with cognitive status in persons with AD and aMCI. Frontal WMH was an important predictor of impaired ability to do shopping and food preparation. A preventive strategy for WMH might lead to suppression of IADL disability and slow the progression of AD. [ABSTRACT FROM AUTHOR]

Aim Hearing loss is a risk factor for the progression of dementia. Cognitive improvement is occasionally found after removal of cerumen impaction. Because patients with dementia do not usually complain about cerumen impaction, detection methods are important. The present study aimed to investigate whether cerumen impaction is observable using brain magnetic resonance imaging. Methods Participants were six patients whose hearing level improved 15 dB or more unilaterally or bilaterally after the removal of cerumen impaction. A radiologist who was blind to the impaction side and whether magnetic resonance imaging scans were taken before or after impaction removal classified cerumen impaction as positive, negative or unclear. Results Three ears classified as impaction positive and five ears classified as impaction negative corresponded accurately to the presence or absence of cerumen impaction. Among four ears classified as unclear, two did and two did not have cerumen impaction. Conclusion Careful examination of the external ear canal on brain magnetic resonance imaging can be used to detect cerumen impaction. Geriatr Gerontol Int 2015; ●●: ●●-●●. [ABSTRACT FROM AUTHOR]

Aim To assess the effect of cerumen impaction and its removal on hearing ability and cognitive function in elderly patients with memory disorders in Japan. Methods Pure tone audiometry ( PTA) and the Mini- Mental State Examination ( MMSE) were administered to participants before and after cerumen removal. Participants who had cerumen impaction in the better-hearing ear comprised the case group; the control group consisted of participants who either did not have cerumen impaction or had it in the worse hearing ear. Hearing and cognition changes were compared between the groups after cerumen removal. Results A total of 55 patients who completed all examinations were assigned to the case group (29 patients) or the control group (26 patients). The average hearing change was 4.6 ± 7.4 in the case group and 0.9 ± 0.9 in the control group ( P = 0.029). The average change in MMSE score was 0.7 ± 2.5 in the case group and −1.0 ± 4.1 in the control group ( P = 0.068). The case group showed a significant improvement in MMSE scores after age adjustment compared with the control group ( P = 0.049). Conclusion Hearing improved significantly in the case group relative to controls after cerumen removal. A significant cognitive improvement in the case group relative to controls was additionally observed after cerumen removal with age adjustment. Thus, the present results suggest routine ear canal examinations might benefit elderly individuals with memory disorders. Geriatr Gerontol Int 2014; 14 (Suppl. 2): 56-61. [ABSTRACT FROM AUTHOR]